From Foot Pain to Lung Cancer: Kathrin’s Unexpected Stage 4 ALK+ Diagnosis
When Kathrin was diagnosed with stage 4 ALK+ lung cancer in 2024, it came as a complete shock. She didn’t have a cough, chest pain, or shortness of breath — none of the symptoms you’d expect. Instead, it all started with subtle signs: persistent fatigue, frequent illness, and a lingering pain in her left foot that she chalked up to an injury.
Being a fitness professional, Kathrin assumed it was nothing serious, but after the pain worsened, an MRI revealed something unexpected: a tumor in her foot. Initially thought to be benign, the biopsy showed it was a malignant metastasis. From there, a full-body PET/CT scan uncovered the real culprit: stage 4 ALK+ lung cancer, which had already spread to her bones, abdomen, and liver.
Despite the shock and the immediate fear of not surviving, biomarker testing provided a silver lining. Kathrin was ALK-positive, making her eligible for targeted therapy. Treatment began with radiation on her foot, followed by a daily ALK inhibitor pill. Within weeks, the treatment produced remarkable results.
Kathrin’s scans looked almost clear, which felt like being handed back her life. She describes this part as surreal, going from imagining death to being filled with hope. While the physical treatment has gone well, the emotional part has been more complex. Even though the cancer was under control, the reality of living with an incurable condition remains. She knows it may come back, so she consciously chooses to focus on what she can control: her mindset, her movement, and her moments of joy.
Exercise has been Kathrin’s anchor. Even during radiation, she kept moving. For her, movement isn’t just fitness; it’s therapy. It’s how she reconnects with herself, processes her emotions, and taps into her inner strength. She emphasizes the importance of staying active, not just for the body but for mental clarity and emotional balance.
Her story highlights a powerful truth: stage 4 ALK+ lung cancer doesn’t always look like what we expect, especially in women. Kathrin’s experience is a reminder of the importance of advocating for your health, listening to your body, and honoring your strength, even when life throws something unimaginable your way.
Watch Kathrin’s full interview to learn more about her story:
She had no cough, just foot pain. That’s how her stage 4 ALK+ lung cancer was discovered.
Kathrin opens up about the emotional whiplash of a sudden diagnosis.
How yoga and exercise became her daily lifeline through stage 4 ALK+ lung cancer.
Why Kathrin believes powerful treatments and positivity can change everything.
Name: Kathrin W.
Age of Diagnosis:
44
Diagnosis:
Lung Cancer
Staging:
Stage 4
Mutation:
ALK+
Symptoms:
Weakness
Decline of performance in sports
Depression
Pain in left foot
Treatments:
Radiation therapy
Targeted therapy
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
Why Speaking Up Matters: Dorinda’s Life with Bladder Cancer
When life threw curveball after curveball at her, she didn’t flinch; she adapted. She was living in a fifth-wheel trailer on her parents’ property, helping care for her dying mother, when she noticed something alarming: a significant amount of blood in her urine. While she initially thought it might be a urinary tract infection, her instincts told her otherwise and she was right. It turned out to be bladder cancer.
Navigating the healthcare system wasn’t easy, but she stood firm, advocating for herself by insisting that something was wrong. That determination led to a cystoscopy, where a tumor was found on her bladder wall. She describes it looking almost like a piece of coral — strange, fascinating, and life-changing.
She had never heard of bladder cancer before her diagnosis. Like many, she associated cancer with more commonly discussed types, like breast or lung cancer. But her diagnosis opened her eyes to how little awareness exists about bladder cancer, especially in women.
Her care team, especially her urologist, played a major role in helping her feel empowered. He explained everything clearly and respectfully, building trust. When he told her, “You’re going to be fine,” she believed him. That kind of confidence, paired with open communication and mutual respect, made all the difference.
Treatment involved a transurethral resection of bladder tumor (TURBT) surgery and intravesical BCG therapy, which hit her hard with fatigue and other side effects. Despite this, she showed up — until she no longer could. She decided to stop maintenance BCG, fully informed and supported by her doctor. Later, when a growth appeared in her bladder, she underwent surgery again, followed by intravesical chemotherapy. Thankfully, it wasn’t cancer.
Throughout her experience, she became her own best advocate — asking questions, researching treatment options, and connecting with others online. Sharing her story on social media not only helped her process what she was going through but also gave others a sense of community and hope. She encourages everyone to speak up, take notes, and never feel guilty for asking questions because your voice matters.
She reminds us that people living with bladder cancer deserve compassion, informed care, and access to all possible options. Most importantly, they deserve to be heard.
Name: Dorinda G.
Age at Diagnosis:
59
Diagnosis:
Non-Muscle Invasive Bladder Cancer (Malignant Neoplasm of Bladder Trigone)
Symptom:
A significant amount of blood in the urine
Treatments:
Surgery: transurethral resection of bladder tumor (TURBT), surgery for papillary lesion
Immunotherapy: BCG (initial and maintenance)
Chemotherapy
Thank you to Johnson & Johnson for supporting our patient education program. The Patient Story retains full editorial control over all content.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
People describe me as being strong. I’m divorced and I’ve raised kids on my own. I’ve survived cancer and domestic violence. I didn’t let what happened stop me or slow me down. I’ve looked at everything that’s happened to me as an opportunity for learning and growth.
During the pandemic, some circumstances came up and I needed a place to live. Since everything was shut down, I couldn’t view rental properties. Prices went through the roof, doubled and tripled in some cases.
My mom was ill, bedridden, and on hospice care. My parents needed me close by, so I bought a used fifth wheel in fair condition and parked it on their property. That’s where I was living when I was diagnosed. I helped care for my mom until she passed.
When I turned 59, one thing after another started to happen. I was taken to the emergency room, where they found out that my gallbladder was full of gallstones and I had a blockage. It caused a lot of issues with my liver. They had to get everything under control before they could send me home, so I was in the hospital for four or five days. A couple of months after that, I found out I had bladder cancer.
But how I view things is: what other option is there? Lying down, playing victim, and saying woe is me was never an option. The choice was to keep going and keep doing. You do the best you can every day and get through it.
When I Knew Something Was Wrong
I saw a significant amount of blood in my urine. I had recurrent sinus infections, so I scheduled a visit with whoever was available at my doctor’s office to get in right away.
I knew the assistant who was checking me in and she asked how I was doing. I said, “It’s just another sinus infection. But there’s one other thing. There’s a lot of blood in my urine.” She said, “Oh my gosh. Let’s get you into the bathroom. I’m going to set you up. We need a sample.”
Right away, she did everything she needed to do. When the provider came in to talk to me, he tried to explain that I wasn’t seeing blood in my urine, but it must be something I ate. I told him, “I’m 59. I’ve had five children. I think I know very well what blood looks like in the toilet and a lot of it.”
As the results come up on his computer screen, he says, “Oh my God, that’s a lot of blood.” I’ve never gone back to that provider again. He was trying to dismiss my symptom. It’s a real problem in women’s health across the board for all various kinds of reasons, especially — and unfortunately — with male providers. If you look at the history of medical research, women are blatantly ignored concerning their symptoms. Men are researched more than women.
The cystoscopy was uncomfortable but manageable. It wasn’t painful at all.
Imagine a woman on her menstrual cycle seeing blood in the toilet; it was like that. It was a significant amount of blood and I knew that. It wasn’t a spot on the toilet paper.
It started with tiny spotting around three to five days prior, which was thought of as possibly a urinary tract infection (UTI). I may not be remembering clearly, but I think I was given a round of antibiotics, and the amount of blood kept increasing.
I happened to also be sick and wanted to be seen for that sinus infection, so I decided to tell them about the blood because I knew that something was wrong. That wasn’t normal. There was no pain with urination. There wasn’t any pressure. There were no other symptoms.
When thedoctor saw the result of my urine test, I was given a quick referral to a urologist.
Cancer Research UK / Wikimedia Commons
The Moment Everything Changed
My initial appointment was with the physician assistant (PA) in the urologist’s office. We discussed what was going on and I gave another sample for a urine test, which they sent off to check for cancer cells. When they called me back, they said, “Great news. There are no cancer cells in your urine, but we still want you to come in and see the urologist for a cystoscopy.” Lo and behold, they found a tumor.
What My Cystoscopy Was Like
The cystoscopy was uncomfortable but manageable. It wasn’t painful at all. You undress from the waist down and put your feet up in the stirrups. They use lidocaine at the opening of the urethra, which helps tremendously.
They insert the scope, which looks like a catheter with a camera at the end, through your urethra to see into your bladder. There was a screen facing me, so I could see everything that he saw. Everything was explained to me.
I understand it’s a lot different for a man. My son-in-law recently had one and he did not have a good experience at all. I think it’s different for him because our anatomies are different, which I think makes it less traumatic for a woman. I may be completely wrong because I only know from my experience. I don’t look forward to it, but I go every time they ask me to come in for one.
My urologist listened to me. I feel heard.
Partway through treatment, I got COVID at the same time I had my BCG treatment, and the side effects were compounded exponentially. I was very ill. I was so fatigued and couldn’t get out of bed. It was pretty bad, so I declined further maintenance treatment.
It was very interesting and pretty fascinating because the tumor looked like a little sea anemone or piece of coral. It had a funky shape and was stuck on the bladder wall. After the cystoscopy, he gave me a one-dose antibiotic right away to help stave off any kind of UTI. He took me into his office and brought out all the pamphlets on bladder cancer.
During the scope, he didn’t say that it was cancer. I credit him for my reaction to it because his bedside manner was outstanding. He was very confident. He said, “This is what it is. We’re going to remove it. Then we do this treatment and you will 100% be fine. You are going to recover.” He was so confident. I put my trust in my urologist. He’s amazing.
I was involved in an online journey mapping. Several patients, caregivers, and doctors had experience with bladder cancer. I was listening to other people’s stories with their providers. I felt so incredibly fortunate to have the provider I have. Listening to other people’s stories made me feel so grateful for my experience.
I’m Grateful That My Doctor Listens to Me
The big thing for me was that my urologist listened to me. I feel heard. I provide him with that same respect and listen to him because he has the expertise. He understood why I wanted to stop the maintenance treatment. We discussed what that would look like in the future if there’s a recurrence and I understood. He made everything very clear.
He honored my decisions and didn’t try to sway me. We discussed the potential consequences of stopping treatment, but I still went ahead.
I had missed so much work. Part of me was afraid of how long my employer was going to let me miss work, but they were very understanding. After a while, though, you cannot afford not to be paid. Everybody has to have an income. It was affecting my life. At that point, I felt like it wasn’t going to come back and that I had a handle on it.
I agreed to keep coming in every 90 days for a cystoscopy to be checked, which was good because by December, I had a growth in my bladder.
How I Felt After Finding Out I Had Bladder Cancer
I was in shock. I was texting my adult daughters from the office, telling them I have cancer. It’s something that you see happens to other people, but don’t think it would happen to you, but now it is.
Cancer’s a scary word. It’s a scary diagnosis because the cancers that we see and hear about most often don’t always have good outcomes. I didn’t even know about bladder cancer until I got it. I’d never heard about it. I had no idea that you can get cancer in the bladder.
It was very surreal. It was a lot of information to absorb. I didn’t cry or freak out. I credit my urologist for that because he was so good at talking me through all of it. I felt confident that after I get this procedure done and do this treatment, I’ll have done it.
The last time I saw him, I talked to him about it. I told him that after hearing other people’s stories, I couldn’t thank them enough. I have the same nurse every time I go in. My care team is phenomenal and I’m grateful for that, especially after hearing other people’s stories.
I didn’t have a lot of emotions. I looked at it as fact. This is what’s happening and this is what’s going to happen next. During treatment, there was a time when I was in a very negative headspace. When I went to my appointment, I told them, “I don’t want to be here. I don’t want to do this anymore. I’m done. I’m over it. I’m here because I know I have to. I know this is what’s best, but I don’t want to do it anymore.”
I was sick and tired of having medication put into my bladder. I was tired of undressing from the waist down. I was tired of putting my feet in stirrups. I was just over the whole experience. I had my first BCG treatment in June 2023. By January 2024, I started getting that feeling of not wanting to do it anymore and by September, I said I didn’t want to continue with the maintenance treatment.
On one of my TikTok videos, some people asked me about discontinuing the maintenance treatment and whether you’re allowed to do that. My doctor didn’t say I could stop. He understood where I was coming from.
I agreed to keep coming in every 90 days for a cystoscopy to be checked, which was good because by December, I had a growth in my bladder. It turned out to be non-cancerous, thank goodness, but I still had to go in and have it removed through surgery and have the pathology done. At that time, we didn’t know. Because it looked like the original tumor, we did chemotherapy in the bladder in December.
I communicated with people through my videos, which helped me deal with what I was going through.
Learning More About Bladder Cancer
I read the bladder cancer pamphlets multiple times. Then I would get online and Google everything, like most people do. I did a lot of research online as well and the information I found aligned with everything in the pamphlets. I had to keep rereading and reaffirming myself.
I researched what bladder cancer is and what the treatments are, and BCG was the gold standard. I’m hearing more recently that there are alternative treatments, which is good because of the global shortage of BCG. In some areas of the country, I learned from other bladder cancer patients that they have not had access to BCG. I felt fortunate that it was available to me.
Having Support Around Me
My daughter Madeline took me to every appointment. She also stayed with me because when you come home, you have to lie down and rotate every 15 minutes until it’s time to go to the bathroom. She was my major support person.
I have met other bladder cancer patients who are much better with their social media than I was. When I started sharing, it was my way of dealing with it and processing it. Somebody who saw my TikTok video found me on Facebook. She reached out on Messenger to check in with me every Thursday. She was just diagnosed and hadn’t started her treatment yet, but she would ask how my treatment went and how I was doing.
I communicated with people through my videos, which helped me deal with what I was going through. I know people who have had breast cancer. I had a nephew who had childhood cancer. But I didn’t know anyone with bladder cancer.
How did I get this? Where did this come from? I thought if I started talking about it and put myself out there a little bit, other people would come forward or somebody would learn something. I wanted to get the word out.
The possibility of bladder removal was mentioned… We didn’t discuss it because he was very confident that removing the tumor and the BCG treatment were going to be effective for me.
Discussing Bladder Cancer Treatment Options
My urologist talked to me about treatment options immediately because I had to get the surgery scheduled ASAP. I asked if we could wait until the school year was over because I didn’t want to miss work. He said no and that it had to be done immediately.
He never gave me a stage, but I know that the two-centimeter tumor was a mix of high-grade and low-grade cancer, which he was surprised about. Based on his experience and from what he saw, he was pretty sure it was low-grade cancer.
There weren’t any options. It was going to be the transurethral resection of bladder tumor (TURBT) surgery and the BCG treatment. With the BCG, he explained what it is, what it’s used for in other countries, and what we use it for here in the US, which is to treat bladder cancer.
He talked about the BCG shortage and the possibility of it not being available. If we ran into that issue, then we would discuss other options. Thankfully, it was available and I got it every time I needed it.
The possibility of bladder removal was mentioned in all the literature that he gave. We didn’t discuss it because he was very confident that removing the tumor and the BCG treatment were going to be effective for me.
I didn’t even know about bladder removal. After I’d gone through all of this, I found out that I had an uncle who had bladder cancer and had his bladder removed. Nobody in the family ever knew until I started talking about what I was going through.
My cousin was pretty vague about it, but they were aggressive with what they did. They found out later that they didn’t have to do the bladder removal, but they went forward with it because he felt that he was getting rid of the potential recurrence. I’m not 100% sure what happened.
Different doctors have different approaches. My urologist was pretty conservative, but it’s also been very positive. Everything so far has been right for me.
I could have spoken up and said I didn’t want to do the treatment, but why would I? He’s the expert. This is what he does. He knows what’s best and I felt very confident in his skills and his decisions. I trusted him 100%.
I was in a very negative headspace… I couldn’t do anything. I didn’t have any energy. I didn’t feel like myself.
Why I Decided to Stop Maintenance Treatment
With BCG, I had to go in once a week for six weeks for the initial treatment. A lot of people have very minimal side effects from it. For me, I was down for anywhere from two to four days. I was wiped out and felt extremely fatigued. I’ve never experienced that before. That’s something he noted in my charts, which is that I didn’t respond favorably.
My initial round of BCG treatment was during the summer, so I was off work. I got a little bit of a break and then I went back for three weeks of maintenance treatment. Then I had another break and went back for another three weeks of maintenance treatment. By September 2024, I said I couldn’t do it anymore.
Between January and September, I was in a very negative headspace about everything. I was tired of being tired and of feeling like I couldn’t get out of bed every day. I couldn’t do anything. I didn’t have any energy. I didn’t feel like myself.
Cancer Research UK / Wikimedia Commons
Getting Intravesical Chemotherapy for the Recurrence
He had mentioned that if it recurs, I would probably have to do the chemotherapy into the bladder. But he didn’t say any drug names, just that it was chemotherapy. They do it through a catheter, the same way they do BCG, but from what I understand, it takes longer and you’re in the office longer because I think you have to wait there.
None of those things have been thoroughly discussed with me because I’m assuming it wasn’t necessary. But in December, I had intravesical chemotherapy. They inserted it through a catheter and clamped it. It’s held in for an hour and then they pull the catheter out. I’ve only had it one time.
The Side Effects of BCG Treatment I Experienced
My treatment day was always on a Thursday, so I had to miss that day of work and the following day. Because of the side effects, I couldn’t function. Sometimes, I would even miss work the following Monday, so that’s at least two to three days a week of work. Then I have to repeat it all the following week.
For me, I would get the chills and feel extremely fatigued. I’ve never experienced anything like that before. I was weak and tired. I couldn’t even hold my phone. I couldn’t get out of bed. I couldn’t do anything. I lay in bed and slept around the clock.
I don’t think bladder cancer removal should be an option unless it’s absolutely necessary.
At one point, I had COVID while having treatment at the same time. That was a rough three weeks. I was at the point where I couldn’t do it anymore. I physically couldn’t. I had what they called long COVID because it took a good six to eight months for me to get over all of the symptoms. Undergoing BCG treatment at the same time did not help me feel better.
The Advantages and Importance of Having Treatment Options
I think it’s good news. I do like that because there’s a worldwide shortage of BCG. Whether or not it’s the gold standard, if you can’t get it, you have to have alternatives. We’ll find out in time if the alternatives are better. All medical advances are good. Something that’s tried and true doesn’t always mean it’s the single best treatment because something better could come along.
Bladder cancer has a high recurrence rate, so there’s always a chance that it will come back. Knowing that there are advancements and new treatments, if it comes to that, then I can talk to my urologist and find out what’s available and what’s different.
I would want to consider the side effects and how they’re going to affect my life and my ability to work and function, and the effectiveness. In the grand scheme of things, of course I would like fewer side effects, but if something’s not going to be as effective, then I’m going to have to suck it up and go with what’s most effective.
I don’t think bladder cancer removal should be an option unless it’s absolutely necessary. Has there been multiple recurrences? Is the tumor invading the muscle now? Is it growing? I had non-muscle invasive bladder cancer, so why would I do that?
For me, that would be the extreme option in my situation. I want to continue to live and have a good quality of life, but I don’t think bladder cancer should be discussed as an option unless it’s a necessary course of treatment.
Doctors need to be open-minded and explore the new options coming out. Think about your patients: who they are, their age, their activity level, and their lifestyle. What do they do for a living? What do they do for recreation? Then think about the treatment options.
What treatment can improve the quality of life of my patient? What’s going to give them fewer difficulties? What’s going to interfere the most and what’s going to interfere the least? What treatment would be the least impactful in terms of side effects?
Don’t be afraid to speak up. Don’t be afraid to ask. You are your own best advocate. If you don’t speak up, who else will?
I want medical professionals to see us as human beings. Yes, we have this condition. Yes, you are the expert. But we also have a life outside of our condition.
How You Can Advocate for Yourself
I’ve been a paraprofessional in special education for over 30 years and I’ve had to advocate for students who can’t advocate for themselves. I’ve always been that way.
Ask questions. Do the research. In December, when I had the growth removed from my bladder and my doctor started talking about intravesical chemotherapy, I started spouting percentages back to him about how that was going to reduce the rate of recurrence. He was chuckling and I said, “I’m sorry, but I did my research because I wanted to know,” and he thought it was great. He was pretty impressed because I don’t think he expected it from me.
Don’t be afraid to speak up. Don’t be afraid to ask. You are your own best advocate. If you don’t speak up, who else will? You may have a caregiver, a spouse or a significant other, a parent or an adult child looking out for you, but we have to advocate for ourselves.
If you have questions, jot them down. Make a note in your phone or a notebook. Write your questions and concerns down, and bring them up. Talk to your nurses, to your doctor, and to everybody there. They’re a wealthy source of information. I don’t think that puts anybody in a negative light. We should be as informed as we can be.
How did I get this? I was never a smoker. I don’t work in the agricultural industry where I’m exposed to pesticides and chemicals, because he did ask me about that. But I have, unfortunately, put myself in situations where I’ve been exposed to second-hand smoke throughout my life.
Now I’m very cautious about my exposure. If I go out for a drink with friends, it’s in a nonsmoking bar. I won’t hang out in a garage or a shop where people are smoking. I’m limiting my exposure to reduce any risk because I take it very seriously.
Special thanks again to Johnson & Johnson for supporting our patient education program. The Patient Story retains full editorial control over all content.
Symptoms: Irregular occurrences of seeing streaks of blood in urine, specific type of pain when bladder is full, unexplained weight loss, urinary urgency, malaise, fatigue Treatments: Chemotherapy, surgery (TURBT: transurethral resection of bladder tumor)
CLL Treatment Advances: Moving from Research to Reality
Targeted Therapies, Breakthrough Combinations, and Minimal Residual Disease (MRD)
The world of CLL treatment is evolving fast, with new breakthroughs offering more options and greater precision than ever before.
This program brings together expert Dr. Jeff Sharman and patient advocate Andrew Schorr to break down the most important updates from recent research and clinical trials. Learn what’s changing, how it impacts treatment decisions, and what it all means for patients today.
Webinar: CLL Treatment Advances: Moving From Research to Reality
Hosted by The Patient Story
The world of CLL treatment is evolving fast. This program breaks down the most important updates from recent research and clinical trials. Learn what’s changing, how it impacts treatment decisions, and what it all means for patients today.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
Thank you to AbbVie for its support of our independent patient education program. The Patient Story retains full editorial control over all content.
Stephanie Chuang: Welcome to “CLL Treatment Advances: Moving from Research to Reality,” a program focused on all of the latest in research and clinical trials in the world of CLL treatment. It’s a space that we know has experienced so much development in the last few years especially. While that’s incredible news, it also means that there might be more questions about CLL treatment options. We are featuring some incredible CLL advocates on the topic from both the specialist side and the patient side.
I’m the founder of The Patient Story and I was diagnosed with a different kind of blood cancer, an aggressive form of non-Hodgkin lymphoma. While I was undergoing hundreds of hours of chemo, the idea for The Patient Story came up. I thought that other people would want humanized information the way that I did and that’s what we try to do. We help people navigate life at and after diagnosis in human terms and build community through in-depth patient stories and educational discussions.
We want to thank our sponsor, AbbVie, for supporting this program, which helps us host more of these discussions for free. I want to stress that, as always, The Patient Story retains full editorial control over all content. While we hope that this is helpful, keep in mind that this is not a substitute for medical advice so still consult with your health team about your decisions.
There’s so much to get through, so I will hand it over to someone many of you are very familiar with and who I’m proud to say has become a friend of mine, Andrew Schorr.
Andrew Schorr: Hello and welcome to this program. We’re going to discuss the latest in CLL, particularly based on one of the big medical meetings that happened not too long ago where a lot of studies came out. What does it mean for all of us? I’m in San Diego and I’ve been living with CLL since 1996.
Dr. Jeff Sharman: It’s great to be back with you, Andrew. Thanks for having me.
What Happens After a CLL Diagnosis?
Andrew: Jeff, I’ve been living with CLL for many years. Some people who will watch this program are newly diagnosed. I went through all the stages and I’m sure you see it in your practice daily. “What the hell is this? I’m scared. I have a blood cancer. Will my life be shorter? Am I going to die anytime soon? What do you have that’s effective to treat me? If that doesn’t work, do you have something else?” We’re going to get into all that, but at a high level, Jeff, how do you feel for today’s patient?
As a doctor, one of the things is figuring out how to administer the most unique medicine we give, which is the medicine of hope
Dr. Jeff Sharman
Dr. Sharman: I have a very large practice. I take care of about 400 CLL patients and for many of them, I’ve been their first doctor. That’s the nature of my practice. For a lot of folks I take care of, I’m their first contact in terms of understanding CLL.
What you highlighted is something I see time and time again, which is a very understandable fear patients come in with. It’s very common. You say leukemia and you see their eyes widen and see them sit up a little straighter. What you recognize is a great deal of distress that any cancer would cause. As a doctor, one of the things is figuring out how to administer the most unique medicine we give, which is the medicine of hope, and communicate that with patients in the midst of some of the worst days of their lives.
I do reference quite frequently a study done in the Italian group, which showed that if you’re age 65 and above diagnosed with CLL, you can’t measure a statistical impact on survival. Most patients are going to outlive their diagnosis and that’s an optimistic message. Most patients aren’t going to pass away from their disease and that bears out from my experience. The number of patients who die from complications of CLL is a very small fraction. Even in my large CLL practice, it’s only a small number; two or three per year might be the case. We have a lot of treatment options for CLL apart from the traditional chemotherapy. We have targeted agents, immunotherapy, and so forth.
Most patients are going to outlive their diagnosis and that’s an optimistic message.
Dr. Jeff Sharman
Andrew: The bottom line is most of us are going to live a pretty normal life. We may need to take medicines along the way, but we have more effective medicines than ever before and others that are very promising.
The Latest Treatment Options for CLL
Andrew: I was diagnosed in 1996, but I wasn’t treated until 2000. At that time, the feeling was that treatment might be more harmful than waiting and seeing what happens. There’s still a percentage of patients who never need treatment.
I was in a clinical trial of fludarabine and cyclophosphamide with rituximab. It led to a 17-year remission, but it had the chemo component. I had a treatment that sometimes comes into play years later, which was high-dose methylprednisolone with obinutuzumab. That was about seven years ago and I’ve never had any treatment since then.
Each year, there are several meetings where you discuss the latest in research in CLL, but the big meeting in December 2024 was the American Society of Hematology meeting or ASH. The impression I had, Jeff, was we have several approved therapies, but we have what looks like planes circling the airport at different altitudes — stage 1, stage 2, stage 3 — that are very promising and are waiting in the wings for CLL. We will get into the details, but am I right that we have a lot coming?
Dr. Sharman: A lot is coming, Andrew. At these meetings, we get to see a cross-section of development. We see all those airplanes in various stages of flight. Some are coming in for landing, some are still on the assembly line, some are mid-flight, and so forth. There are severeal reasons to be optimistic about what’s out there.
Andrew: Let’s understand where we are with approved therapy. I had some chemo years ago, but you mentioned that people aren’t going to need chemo. We have this whole class of medicines — BTK inhibitors — and even new generations of that we can talk about. With the approved therapies, you have quite an arsenal now where you can use drugs either by themselves or together.
Dr. Sharman: There are three main classes of drugs. You mentioned BTK inhibitors. I would add BCL-2 inhibitors and immunotherapy, particularly obinutuzumab, which goes by the commercial name Gazyva. It took a lot of work to get each of these drugs approved. Right now, we’ve learned how to combine these drugs in terms of what we call doublet therapy, where we use two of those drugs together, and even triplet therapy, where we put three of them together. What the field is trying to figure out is the best combination and the best sequence.
The good news is these drugs are FDA-approved and available to patients. When most patients think about chemotherapy, they think of the traditional drugs developed from the 1950s through the year 2000. Those are drugs that typically damage DNA and cause cells to die as a result of damaging DNA.
What’s different now is we have these targeted therapies, which have no DNA-damaging component but instead exploit certain vulnerabilities of the cancer cell. There’s an enzyme sequence or a signaling mechanism inside a cell. I like to think of it as an electrical current, which needs to keep going to keep the CLL cell alive. What BTK inhibitors do is cause a short circuit in that electrical circuit, so the cancer cells die as a result. It turns out that the cancer cells are more sensitive to it than normal healthy B cells. It’s a targeted therapy. It doesn’t damage DNA. It exploits a certain vulnerability.
BCL-2 inhibitors are similar in that the cancer cells are dependent upon this enzyme called BCL-2, which helps keep the cell alive. If we disrupt BCL-2, it’s almost like taking off the fence from around the Grand Canyon — they fall in and the cancer cells die as a result. It gets rid of the safety mechanism for the cells.
With obinutuzumab, what we’re doing is recruiting the immune system to fight off the cancer of the immune system. It’s as though we’re giving the immune system the tools it needs to fight off the cancer that’s already there.
Each of these drugs has its side effects. There’s no such thing as a drug that doesn’t have side effects, but in contrast to traditional chemotherapy, it’s not the same type of patient experience. These aren’t nausea-provoking drugs and they certainly don’t cause hair loss. In a lot of cases, these drugs are pretty easy to take side by side with the rest of your medications and you might not necessarily know there’s something unique about it, if that makes sense.
Andrew: As far as BTKs, we have ibrutinib (Imbruvica), acalabrutinib (Calquence), zanubrutinib (Brukinsa), and pirtobrutinib (Jaypirca). For BCL-2, we have venetoclax (Venclexta) and others in development. Many people are taking BTKs now. How do you determine who gets what?
Dr. Sharman: There’s a lot of terminology around first-generation, second-generation, and third-generation. We’re researching fourth-generation BTK inhibitors.
The very first BTK inhibitor to come about was ibrutinib, which turns off the BTK enzyme in a unique way. It forms a bond with the BTK molecule, which we call an irreversible inhibitor or covalent inhibitor. It forms a permanent attachment to the BTK enzyme so that particular enzyme will never work again until the cancer cell makes a new one. Cancer cells make new ones and in about 24 hours, they’re starting to wake up their BTK, which is why ibrutinib is taken once a day. The new enzyme needs to be shut down, just like the old enzyme was.
There are some unique side effects with ibrutinib. We see an increased rate of bruising and bleeding, which tends to be mild arm bruising. For most patients, it doesn’t prove to be all that much, but a lot of our patients are already on blood thinners so if you start adding them together, the risk of bleeding goes up. We see some joint aches and muscle cramps happen. Occasionally, patients can have an abnormal heart rhythm called atrial fibrillation. Originally, we didn’t know if that came from the drug, but we’ve largely concluded now that it does.
That left room for the second-generation BTK inhibitors, acalabrutinib and zanubrutinib. These medications underwent more rigorous pre-clinical development of medicinal chemistry to try to dial out some of those side effects. In fact, acalabrutinib and zanubrutinib have been compared head to head against ibrutinib in various studies and have shown fewer side effects for most patients and some increased efficacy. Within the field, most doctors who follow this area closely tend to start patients on either acalabrutinib or zanubrutinib.
How do we pick? Sometimes it’s an insurance issue. Sometimes you might have some bias. The cardiac differentiation is a bit in favor of acalabrutinib. In the head-to-head study where zanubrutinib was compared to ibrutinib, there may be a signal of higher efficacy. If you’re going to combine it with obinutuzumab, you go with acalabrutinib. There are various reasons you might pick one over the other. Sometimes it comes down to insurance, but I view acalabrutinib and zanubrutinib as more similar than different.
What is Pirtobrutinib?
Andrew: You used the term covalent. I understand there are non-covalent BTKs and I believe pirtobrutinib is one of those. What’s the difference?
Dr. Sharman: We talked about acalabrutinib and zanubrutinib as second-generation BTK inhibitors because they differentiate from ibrutinib. We consider pirtobrutinib a third-generation BTK inhibitor.
When we talk about the different generations, what’s the main difference? It’s a non-covalent inhibitor. Over time, patients can develop resistance to the first- and second-generation BTK inhibitors and the most common way they do that is by modifying the exact spot on the BTK enzyme where the first- and second-generation BTK inhibitors bind. There’s an amino acid in position 481 called cysteine that can get mutated. All of a sudden, those drugs don’t work. There are other mutations, but that’s the most common one.
Pirtobrutinib does not require forming a bond. It stays in the system a little bit longer, fits into the binding pocket more easily, and doesn’t require that irreversible bond. Pirtobrutinib has been shown to work even after patients have developed resistance to the first- and second-generation BTK inhibitors and that’s what differentiates it as a third-generation BTK inhibitor.
Another one in late development is called nemtabrutinib, which may or may not get approved — I suspect it will. It may still be a little ways away and has flown under the radar a little bit. The distinct advantage of non-covalent inhibitors is they can continue to inhibit the BTK enzyme even after the first- and second-generation BTK inhibitors have stopped working.
What is a Degrader?
Andrew: Some of our patients are like mini scientists and are asking about degraders. What are degraders? I know we don’t have them approved yet, but where are they going to fit in?
Dr. Sharman: They would be a fourth-generation BTK inhibitor. I’ll take the cloud-level view. One paradigm in all of oncology is that when you find a good target, a good enzyme to inhibit, or a good surface target, there are always efforts to continue to exploit the therapeutic opportunity of going after that target in new and improved ways. Clearly, one of the improved ways is to work when the other drugs stop working.
BTK degraders get rid of the BTK enzyme completely instead of turning it off.
Dr. Jeff Sharman
The concept of degraders is a lot like pirtobrutinib, although it does it through a different mechanism. It’s designed to inhibit BTK even when the BTK inhibitors have stopped working. Within any cell — cancer cell or regular cell — there is trash disposal for old broken-down proteins. We are constantly synthesizing new proteins and getting rid of the old ones. Degraders glue a couple of molecules together — one that goes after BTK and then the other one designates the protein for the trash heap — and tags the BTK molecule to dispose of this enzyme. Instead of inhibiting BTK, it’s degrading BTK, which is very different. BTK degraders get rid of the BTK enzyme completely instead of turning it off.
BTK degraders are a very active area of research right now. These would be the airplanes that aren’t necessarily coming in for a landing or even mid-flight. They are still getting manufactured and haven’t taken off from the ground.
CLL Treatments Being Studied Now
Andrew: Venetoclax is a BCL-2 inhibitor, which is a different mechanism of action. There are other BCL-2s in development as well. What are some of the names?
Dr. Sharman: Sonrotoclax is probably the one that’s farthest along. There have been a handful of other BCL-2 inhibitors that have gotten out there. Venetoclax is an incredibly effective drug. In fact, it’s so effective that its effectiveness may almost be its biggest liability. It can literally kill cancer cells so fast that the consequences of that can be some electrolyte abnormalities and disturbances that can be life-threatening, which is what we call tumor lysis syndrome where you’re killing cancer cells too quickly. The inside of cancer cells has a lot of potassium and uric acid.
Andrew: Your kidneys can’t keep up.
Dr. Sharman: You can’t keep up. It can clog up the kidneys, cause heart arrhythmias, and so forth. With venetoclax, we start with a very low dose of 20 mg for a week. The following week, we go up to 50 mg. The week after, we go up to 100 mg. Then 200 mg. Patients generally go on 400 mg.
It also has some drug interactions, more for our patients who have acute myelogenous leukemia (AML) or patients on cardiac medications. What we have to do is check labs frequently. We stratify the risk for these patients. Are they low risk, intermediate risk, or high risk? That has to do with how high their white blood cell count is, how big their lymph nodes are, and how their kidneys function, so we follow these patients closely. For a lot of patients, it’s a month with a lot of lab visits. Sometimes, we even put patients in the hospital when we start the medication because we want to be able to jump into gear if they’re high risk.
It has logistical challenges. It’s not used quite as frequently in the front-line setting as BTK inhibitors, which are oftentimes quite simple to give, but it’s a very effective drug. One of the big advantages is it gives very deep remissions. Oftentimes, we’re able to give patients the drug for one year in the front-line setting, two years in the relapse setting, and then stop the medicine. Patients can have remissions that can last multiple years without requiring ongoing therapy. Whereas with BTK inhibitors, once we start them, patients always ask, “Am I going to be on this forever?” I say, “You’re going to be on it as long as it’s working for you.” For many patients, it can be from five to 10 years, which feels like a long time to be on an anti-cancer medicine for patients.
Patients can have remissions that can last multiple years without requiring ongoing therapy.
Dr. Jeff Sharman
Deciding When to Use a Combination of Drugs for Treatment
Andrew: Let’s tie this together. We have BTK inhibitors that work for most people and depending on the side effects you might experience, the health of your heart, or other issues you might have, your doctor would work with you to choose one that’s the kindest on your body. You might combine it with another drug. You talked about doublets or even triplets, so somebody might receive one of these drugs with obinutuzumab. Would somebody get a BTK and a venetoclax?
Dr. Sharman: That leads us to some of the discussions at the 2024 ASH meeting. If we go back in time to a couple of meetings ago, we saw data for the combination of ibrutinib and venetoclax that was compared against one of the standards at that time, which included obinutuzumab with a chemotherapy drug that’s not used much anymore called chlorambucil. The ibrutinib-venetoclax clearly beat obinutuzumab-chlorambucil and interestingly, we had a different opinion depending on where you are in the world as to whether or not it could be approved. That combination was approved in most of Europe and is reimbursed by insurance in several jurisdictions. In fact, ibrutinib-venetoclax is a very common regimen utilized in Europe.
The combination of acalabrutinib-venetoclax or the triplet acalabrutinib-venetoclax with obinutuzumab was compared against two of the harder chemoimmunotherapy regimens.
Dr. Jeff Sharman
Interestingly, there was a different take on the US regulatory environment. There were some technical reasons that had to do with some of the side effects of combining ibrutinib with venetoclax. Diarrhea was considerably more common and this was in an older population. It was a harder regimen in older patients. The US did not approve it.
You have this difference between the US and Europe. The combination of ibrutinib-venetoclax is not used much in the United States outside of some studies. It does have an endorsement by the National Comprehensive Cancer Network (NCCN). Oftentimes, you could get it, but it leaves a window of opportunity for other BTK inhibitors, which gets us into some of the discussion at the 2024 ASH meeting.
The combination of acalabrutinib-venetoclax or the triplet acalabrutinib-venetoclax with obinutuzumab was compared against two of the harder chemoimmunotherapy regimens, either fludarabine, cyclophosphamide, and rituximab (FCR) or bendamustine-rituximab (BR). In both experimental arms, the doublet (acalabrutinib-venetoclax) and the triplet (acalabrutinib-venetoclax with obinutuzumab) beat chemoimmunotherapy.
Within the field, there’s an expectation that there will be approval fairly soon for acalabrutinib-venetoclax with or without obinutuzumab, which is attractive to patients because it’s an all-oral regimen. You take the acalabrutinib for a while before you start the venetoclax. It cuts down on the risk of tumor lysis quite a bit. It’s convenient, effective, and fixed duration, so patients don’t take it until it stops working. There are a lot of advantages to that combination and it’s one of the things that we’re expecting to get an approval by the FDA sometime in 2025.
Andrew: To be clear though, obinutuzumab is an infused therapy.
Dr. Sharman: Yes, obinutuzumab is an infused therapy. The triplet includes obinutuzumab, which is an infused therapy.
Andrew: Jeff, it sounds like we’ve got lines of therapy. We have people who you might start on a single drug. You might have a discussion with a patient about fixed duration, putting two drugs together, taking them for a while, and if you can get their disease undetectable or very low, they can stop and see how long that goes. That might be attractive.
Dr. Sharman: We haven’t talked about obinutuzumab-venetoclax as another doublet. We’ve talked about BTK inhibitors. We’ve talked about venetoclax. Most of the time, once somebody starts a BTK inhibitor, they stay on it until it stops working.
Obinutuzumab-venetoclax is generally considered a one-year therapy. Patients start with obinutuzumab, get a sequence of several infusions, and continue on it for a total of six months. We start venetoclax somewhere around month two and go through a careful ramp-up. For those patients, we generally can stop at 12 months. For the molecularly favorable, they may not need therapy for another five, six, or seven years. For some of the higher risk, like the IGHV unmutated population, those remissions might not last quite as long. But one of the big things in the field right now is: what’s the optimal doublet?
Most of the time, once somebody starts a BTK inhibitor, they stay on it until it stops working.
Dr. Jeff Sharman
We have obinutuzumab-venetoclax. We’re likely going to have the approval of acalabrutinib-venetoclax. Which of the two would you rather do? There might be different reasons for different patients. I’m excited about the MAJIC study, which we helped design and lead. The study directly compares obinutuzumab-venetoclax to acalabrutinib-venetoclax. We’re going to learn a lot from that. Do you take it for one year or two years? All oral or IV? That’s one of the big questions in the field. If I’m going to pick a doublet, which two do I pick?
What is CAR T-cell Therapy?
Andrew: Some people will progress and there’s one kind of treatment we haven’t talked about yet: CAR T-cell therapy. Where do we stand with that? My friend Dr. Brian Koffman, who’s gone through many different therapies, had CAR T-cell therapy. It’s a big gun. Where does that fit in for people who don’t do so well on some of these other drugs?
Dr. Sharman: CAR T is an amazing science, Andrew. It’s so amazing to see. The concept here is that we have a patient go through a one-day procedure that is conceptually like dialysis. We take out and isolate their T cells then ship those T cells to a lab. They get reprogrammed in part by the use of a virus that’s been engineered to give the cell different instructions. The cells get manufactured, expanded, and infused back into the patient. It’s amazing, Andrew. The CLL cells get destroyed by these reprogrammed T cells and patients can get very deep remissions.
Now, this is a technology that’s not unique to CLL. In fact, it was first used in CLL and acute lymphoblastic leukemia (ALL). The development in CLL stalled a little bit. But in other diseases, such as diffuse large B-cell lymphoma (DLBCL) and ALL, we feel very comfortable as a field saying that CAR T-cell therapy can be curative in those settings. It is too early to say whether it can be curative in CLL or not. My professional opinion is that for some patients, it could be.
Right now, [CAR T-cell therapy]’s only approved for patients who’ve had both a BTK inhibitor and a BCL-2 inhibitor, but it’s been an effective therapy for a number of my patients.
Dr. Jeff Sharman
The clinical trial that led to the approval of CAR T-cell therapy took the worst of the worst patients who were extraordinarily sick. The data that led to the approval wasn’t the most impressive or compelling; it limped across the finish line. That said, sometimes we design studies to get a drug approved by the FDA and then how we use them in the real world can differ. The opportunity with CAR T-cell therapy may exceed the perception from the study that led to its approval.
Who’s it right for? The reality is a lot of older patients with CLL may not ever need it. Give them a pill, send them on their way, and they’re going to be fine. But the younger they are, the more aggressive the disease, or the combination of young patients with aggressive disease, CAR T-cell therapy is something that needs to be factored into their thinking earlier on. Right now, it’s only approved for patients who’ve had both a BTK inhibitor and a BCL-2 inhibitor, but it’s been an effective therapy for a number of my patients.
We think about treatment sequencing… You need to almost have a game plan in mind for somebody from the outset.
Dr. Jeff Sharman
Working with Your Doctor to Decide on a Treatment
Andrew: In 1996, when I started talking to Dr. Kanti Rai, one of the grandfathers in CLL in clinical research, there wasn’t much to talk about. I said, “Dr. Rai, it seems like you have a lot of furniture in the room and you’re trying to figure out where to put the couch, where to put the easy chair, and how to move things around.” It sounds like that’s where you are now, except you have more furniture.
Dr. Sharman: We’ve lived in the house longer, so it’s more cluttered, and we’ve upgraded the couch.
Andrew: I’m sure there are patients whose heads are spinning. Not all CLL patients are the same and treatment is an individualized choice.
Dr. Sharman: Absolutely. There are some patients who, from the physician’s perspective, I would say, “Oh, this is what we’re doing.” Then there are other patients who are very involved in their care and want to be involved in the decision-making. That’s great and they should be involved.
A patient might have preferences, but I may have different preferences based on how I’m thinking. Sometimes it’s a matter of calling to attention some of the potential side effects in a certain circumstance. Maybe somebody wants to do a fixed duration, but their kidneys aren’t doing well, they have bulky disease, or other reasons why we might pick one over the other.
We think about treatment sequencing. If we’re going to pick this first, what’s the patient going to look like five to seven years from now when we might need to do a second therapy? You need to almost have a game plan in mind for somebody from the outset.
When Do Doctors Decide to Start Treatment?
Andrew: I went four and a half years without treatment and felt pretty good. Then I started to develop some lymph nodes and my white blood count fueled by lymphocytes went up to about 283,000. My friend Dave has a white blood count that’s even higher than that, but he hasn’t had treatment and feels fine. When do you start treatment for a new patient?
Dr. Sharman: Back in the 1950s, steroids were a new thing. This was a byproduct of World War II and we were giving steroids to patients with CLL. In some original manuscripts, patients were getting white blood cell counts of 1.5 million, a number we would never see today. Patients always want to know: At what white count do I need to intervene? The answer is: There isn’t a white count where you need to intervene.
We look at the lymphocyte doubling time (LDT). When that number goes up more than twofold in less than six months, that’s our clue that we need to do something.
Dr. Jeff Sharman
You see doctors get squeamish at different thresholds. If you’re a non-CLL doc, you start to get squeamish around 100,000. If you’re a CLL doc, 200,000 or 300,000 will start to make you nervous. If you’ve been around the block a long time, you have patients who come into your clinic with a white count of 600,000 who are stable. You get desensitized to it.
It’s not a number; it’s a rate of change. It’s not about whether you hit 100, 200, 400, or 600; it’s how quickly your numbers are increasing. For a patient who’s climbing quite rapidly, we look at the lymphocyte doubling time (LDT). When that number goes up more than twofold in less than six months, that’s our clue that we need to do something.
There are other reasons we might treat somebody. When they have bulky lymph nodes, start developing marrow dysfunction, get anemic or their platelets are starting to go down, those can be reasons to intervene. If you treat a lot of CLL, you see some weird ones. I had a patient who had direct kidney involvement with the CLL and had significant kidney problems; that’s not a very common one.
What comes up periodically is fatigue. Some patients have disabling fatigue. They might be 55 years old. They’re not depressed. Their thyroid is fine. They’re not iron-deficient. But they can only go to work for four hours before they have to come home. Disabling fatigue is a reason to treat. These are all pretty well spelled out in the iwCLL criteria: rate of change, symptomatic, bulky lymph nodes, marrow dysfunction, and others. Those are the reasons we treat patients.
I have had some young women, one or two in particular, who were diagnosed at childbearing potential. It’s fine to have kids.
Dr. Jeff Sharman
CLL and Fertility Concerns in Younger Women
Andrew: Another thing that people wonder about is if they’re told they’re diagnosed with CLL and they’re younger and female, would you tell them not to get pregnant?
Dr. Sharman: It hasn’t come up all that much because most women, if they’re going to have kids, will do so before their mid-40s or even younger. The typical age of diagnosis of CLL is 72 with the first line of therapy typically at 74, so it’s not a common scenario. That said, I have had some young women, one or two in particular, who were diagnosed at childbearing potential. It’s fine to have kids. It doesn’t come up often, but it’s not a contraindication.
Addressing Side Effects with Your Doctor
Andrew: We had people who wrote that they had a back rash, a migraine, or this or that. Is it because of the drug they’re taking for CLL, is it the CLL, or is it something else? How do you determine if it’s the drug, the illness, or something else?
Dr. Sharman: There’s obviously no uniform answer to all of that. It’s going to take a close relationship with your oncologist. I always invite my patients to ask questions and do my best as a clinician to say, “Yep, I own that one,” or, “Nope, I don’t think that’s me,” and call balls and strikes. I figure if I’m honest with it and own up to something, then they’ll believe me when I say it’s not on me.
As doctors, we don’t always know. Sometimes it takes working it out together with your patient about how you solve this.
Dr. Jeff Sharman
Even if I’ve done this for a long time, there are times when we don’t know. Sometimes you have to hold the drug for a little while, see if it gets better, restart it, and see if it comes back. You can do that with side effects that are of lower consequence. If it’s a major side effect, like a hemorrhage, that’s a different story altogether. As doctors, we don’t always know. Sometimes it takes working it out together with your patient about how you solve this.
What is Richter’s Transformation?
Andrew: Jeff, there’s a small percentage of patients where you talked about aggressive disease and there’s something called Richter’s Transformation. Could you explain that? One of the patients who wrote in is worried about that.
Dr. Sharman: Richter’s Transformation is a potential complication of CLL that is definitely more concerning. It’s generally when the CLL cell acquires a more aggressive behavior and becomes DLBCL, which is a different entity altogether. It requires a different treatment approach. Generally speaking, we reach for more traditional chemotherapy in that setting. In some cases, it can be fairly resistant to therapy. It’s a disease that can move very quickly.
Richter’s Transformation is rare… But if you’ve had the disease for 20 years, that risk starts to build up.
Dr. Jeff Sharman
If it’s suspected, the clinician has to jump into gear quickly. It requires a biopsy because you have to get a biopsy and prove that it’s not Richter’s Transformation quickly. Most often, you see a lymph node that’s swelling very quickly and disproportionate to the others. If you’re going to get a PET scan, it’s oftentimes bright on a PET scan. These are the things we’re thinking of as a clinician.
Fortunately, Richter’s Transformation is rare. It’s seen in about 1% of patients per year. But if you’ve had the disease for 20 years, that risk starts to build up. It probably hits a plateau at around 15 to 20%.
Sometimes, Richter’s Transformation is misdiagnosed. If you stop somebody on a BTK inhibitor, oftentimes their nodes will increase pretty quickly thereafter and in that circumstance, I’ve seen cases where Richter’s may have been inaccurately diagnosed. It requires a certain degree of suspicion if you’ve got a biopsy right after starting BTK inhibitors.
How Do Doctors Treat Younger Patients with CLL?
Andrew: I know this is complicated for people. We discussed that if you haven’t had treatment, you don’t treat the number; you look at the overall patient. You have a variety of medicines. BTK inhibitors are used by themselves or in combination, and there are different generations. We have clinical trials for some of these treatments mentioned at the 2024 ASH meeting. There are phase 1 trials for BTK degraders. CAR T-cell therapy is for people with more aggressive disease, although we’ll see if that creeps up a little earlier for younger patients.
Some people on Facebook, for instance, are under 50 with CLL and I know it’s not the most common. Is their age of diagnosis a bad thing? Are they going to have a rougher time with CLL because they’re diagnosed younger? Will they not live as long? What do you tell a younger patient based on their age?
Our therapies are as effective in younger individuals as they are in older individuals… we need to come up with something that’s going to keep this disease in control for quite a bit longer.
Dr. Jeff Sharman
Dr. Sharman: For these patients, we have to plan not only for the next 10 to 15 years but also for the next 30 years. To some degree, we celebrate that we have a lot of new tools to control the disease. It is a reasonable question to ask: Can you use these tools to control it for twice as long or three times as long as somebody who’s diagnosed at age 80? It’s a different game plan.
Our therapies are as effective in younger individuals as they are in older individuals and in some cases, maybe even more effective in younger individuals. But it does require some thoughtfulness to think about the fact that we need to come up with something that’s going to keep this disease in control for quite a bit longer.
The field is moving so fast that the tools we’ll be using five to seven years from now may not even have been conceived of at this point. If somebody’s diagnosed younger, it’s fair to assume that there will be more tools in the tool shed down the road.
There’s a general misperception that you would only do a clinical trial if you’re running out of options but it’s not the case at all.
Dr. Jeff Sharman
Considering a Clinical Trial for CLL
Andrew: Some of your patients are on clinical trials. When someone meets with their CLL doctor, should clinical trials be part of the discussion? Do you lay all this stuff out and then say what are in trials that they should consider as well?
Dr. Sharman: Andrew, we treated the very first CLL patient in the world with ibrutinib in my clinic and I’ve been a believer ever since. In many cases, we’re so grateful for patients who’ve volunteered for studies in the past because they’re the ones who’ve moved this field forward.
Clinical trials are not a one-size-fits-all scenario. There’s a general misperception that you would only do a clinical trial if you’re running out of options but it’s not the case at all. There are great studies for previously untreated patients, patients on first relapse, and patients who are resistant to certain treatments. In many cases, for the last 15 to 20 years, some of our best options have only been available in research studies.
It calls for a unique answer for every patient and what sort of studies might be available and accessible to them, but I would definitely like to dispel the notion that it’s only a therapy for patients who’ve run out of options.
Andrew: I was in a phase 2 trial in 2000 for FCR and it led to a 17-year remission, for which I’m very grateful. Would I have had that otherwise?
Concerns About Funding for CLL Research
Andrew: There are challenges about funding for research and researchers are worried. From the point of view of a CLL patient or CLL researcher, do you have a concern where that throws cold water on progress for CLL?
Dr. Sharman: It’s a great question and a sensitive discussion. People are going to have different opinions on this. The funding environment is shifting and I don’t know if we totally understand all the implications. It is worth noting that many studies are supported by the pharmaceutical industry. I know that the pharmaceutical industry is oftentimes considered a bad word, but they’ve been the friends that have brought us a lot of progress in the last handful of years.
The funding environment is shifting and I don’t know if we totally understand all the implications.
Dr. Jeff Sharman
For studies that are sponsored by pharmaceutical companies, these are oftentimes trying to develop a new drug or getting a new drug approved, so I don’t see much impact there. But when it comes to academic, university-based exploratory studies that are grant-funded, some of those will be impacted and some of the basic science research is up in the air right now. People don’t know if grants are going to be renewed or not. Amongst my academic colleagues, there is a great deal of concern and consternation about what the funding changes will mean. The whole story hasn’t been written yet, but like anything, it’s a nuanced answer where some areas will be affected more than others.
Andrew: How many years have you been at it, Jeff? How many years have you been in practice and seeing CLL patients?
Dr. Sharman: I finished my fellowship in 2008 at Stanford and I’ve been in practice in Eugene, Oregon, since then. Fellowship, residency, med school, and undergraduate studies all take a while. I don’t know where you start the clock, but I’m getting gray. How’s that?
Is There a Cure for CLL in Sight?
Andrew: I used to ask Dr. Keating, one of the grandfathers in Seattle, about this. Will we see a cure for CLL in your lifetime? Dr. Sharman, do you have hope for a cure?
Dr. Sharman: Unequivocally yes.
Andrew: I like that answer.
Dr. Sharman: I’ll leave it simple.
The world has changed in the last decade for what it means to be a patient with CLL and it is an area where I think hope is very reasonable.
Dr. Jeff Sharman
Andrew: I like that. When you put it all together, we have a variety of treatments that you can choose from with your patient based on their preference, your recommendations, and their clinical situation. We had some early- and later-stage research at the 2024 ASH meeting in December. Other meetings will happen during the year and then we’ll have ASH again, so we’ll get to talk again. You have different doublets and triplets, and even different ways of doing it. It sounds like there’s great hope for people.
Dr. Sharman: I couldn’t agree more, Andrew. I feel like the world has changed in the last decade for what it means to be a patient with CLL and it is an area where I think hope is very reasonable.
Conclusion
Andrew: Like you, I’ve been at this a while. I was diagnosed in 1996. I’ve seen some sick people, people who’ve been on clinical trials like me, and people on newer medicines. Most people are doing well. My CLL is at a very low level. You may be in long-term remission and though we may not be cured, go live your life. With Dr. Sharman and his colleagues doing the research and the studies that keep coming out, we have every reason to think that we can do that for a long time. Dr. Sharman, thank you so much for being with us and explaining all this.
Dr. Sharman: It’s my pleasure. Thank you so much, Andrew, and I look forward to future conversations.
Andrew: Remember: knowledge — and we’ve been getting some today — can be the best medicine of all.
Stephanie: Thank you, Andrew and Dr. Sharman, for leading this wonderful and very educational discussion at The Patient Story and taking the time out of your very busy schedules to provide such great insights.
Thank you once again to our sponsor, AbbVie, for supporting our independent patient education program. As always, we retain full editorial control. We want to point out some incredible resources from our friends at partner organizations, like The Leukemia & Lymphoma Society and the CLL Society.
The LLS has a community section for people to meet and chat with other blood cancer patients and care partners; in this case, in CLL. The LLS offers many things, but one of the free resources is the Clinical Trial Support Center. It’s free, one-on-one personal guidance throughout the process before, during, and after clinical trials, which, as we know, can be a lot.
The CLL Society has a lot of great programs, too. It’s dedicated to the CLL community and offers programs like Expert Access™, connecting patients to world-renowned CLL experts for a free virtual second opinion, which is so important, especially with all the things that are going on, as you can see from this discussion.
I hope this program was helpful and that you walk away with more knowledge and questions to ask your doctors. Thank you for coming and we hope to see you at another program. Take good care.
Webinar: CLL Treatment Advances: Moving From Research to Reality
Hosted by The Patient Story
The world of CLL treatment is evolving fast. This program breaks down the most important updates from recent research and clinical trials. Learn what’s changing, how it impacts treatment decisions, and what it all means for patients today.
Not Just a Miscarriage: The Rare Cancer Shannon Never Saw Coming
When Shannon found out that she was pregnant, it was supposed to be a joyful chapter in her life. But within weeks, things began to feel off. Spotting led to a heartbreaking miscarriage and a D&C (dilation and curettage procedure) followed. Her doctor mentioned a possible molar pregnancy, but pathology came back negative so she was told to try again. Only, she never really felt better. It would be months before she was told she had a choriocarcinoma.
Even as her symptoms — persistent bleeding, clotting, stomach discomfort — continued to raise red flags, Shannon was repeatedly reassured it was “normal” following a D&C. Deep down, though, she felt something just wasn’t right and things weren’t improving. Months later, she visited a walk-in clinic where a concerned provider decided to look deeper. Another ultrasound led to a second D&C, and this time, pathology confirmed a molar pregnancy. From there, things escalated: she was referred to an oncologist, where she finally heard the word choriocarcinoma (a rare cancer most often occurring in the uterus).
Choriocarcinoma is a rare and aggressive cancer that can arise from placental tissue. Shannon was diagnosed with gestational trophoblastic neoplasia, which later turned into choriocarcinoma. After a series of scans, the cancer was found to be contained in her uterus. Weekly HCG blood tests tracked her progress. At first, the numbers dropped, but when they started to climb again, chemotherapy became inevitable.
She opted for the aggressive five-drug regimen, which required hospitalization. The toll was significant, especially emotionally. Losing her hair was devastating. Life outside of her diagnosis stood still. Shannon described feeling like the world kept spinning without her, while she was stuck trying to reclaim a version of herself she wasn’t sure existed anymore.
Eventually, remission brought relief, but four years later, her symptoms returned. A bloated stomach and a heavy gut feeling turned out to be a second encounter with choriocarcinoma — this time bigger, stronger, and more emotionally draining. Shannon underwent a full hysterectomy and another round of brutal chemo. She preserved her ovaries, which helped her hormonally, but the decision not to have children had long since been made due to the risks.
Throughout it all, Shannon leaned on happy distractions — laughter, humor, connection — and clung to her ability to find light in dark places. She speaks openly about losing parts of her identity, especially her mental state, but is also reclaiming herself piece by piece. Most of all, she urges others to advocate for themselves. If your gut says something is wrong, listen to it. Push for answers. You deserve to be heard, supported, and believed.
Watch Shannon’s full video to find out more about her story:
She knew something was wrong and she was right.
What happens when your body says “stop” and no one listens?
Laughing through chemo? How Shannon found joy even in the hardest moments.
What it’s like to lose part of yourself and slowly build something new.
Why she didn’t ring the bell after beating cancer a second time.
Name: Shannon W.
Age at Diagnosis:
35
Diagnosis:
Choriocarcinoma (gestational trophoblastic neoplasia initially, recurred as choriocarcinoma)
Symptoms:
Molar pregnancy
Vaginal bleeding
Overall feeling of unwell
Cramping
Weight loss
Elevated HCG level
Feeling bloated
Treatments:
Chemotherapy
Surgeries: dilation and curettage (D&C), total hysterectomy
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
Thriving with Multiple Myeloma: Yvonne’s Story of Strength Through Advocacy
Yvonne’s story is one of resilience, hope, and determined self-advocacy. Diagnosed with multiple myeloma in August 2008, Yvonne refused to let her diagnosis define her. She continued living fully, even earning her doctorate while undergoing treatment. Her life wasn’t paused by cancer; it evolved, grew, and took on new meaning.
It all started with sharp pain in her hip after a family trip. What seemed like a sudden injury led to a life-changing diagnosis. Instead of dwelling on fear, Yvonne focused on understanding multiple myeloma and moving forward. Her family was her motivation, especially her daughter, who was just starting college at the time and whom she was determined to watch graduate.
Throughout her experience with multiple myeloma, she prioritized learning and staying engaged. The Winship Cancer Institute of Emory University gave her access to educational materials early on, while she and her family took an active role in researching and understanding treatment options. This curiosity and courage eventually led her to CAR T-cell therapy, one of the most advanced treatments available.
Even when treatment became intense, such as during her stem cell transplant, Yvonne stayed grounded. She was scared, yes, but she asked questions, made informed decisions, and didn’t let fear take over. She delayed one of her treatments to walk across the stage and accept her doctoral degree. That moment represented more than academic success — it was proof of her persistence and belief in living fully despite the diagnosis.
Yvonne also found meaning and healing through advocacy. As a volunteer with The Leukemia & Lymphoma Society, and in particular its Myeloma Link program, she helped spread awareness in her community. She became a role model for those newly diagnosed, showing them that survivorship with multiple myeloma is not just possible, it’s vibrant.
Her advice is to stay positive, ask hard questions, know your options, and be your own advocate. “You can move through it,” she says, “with a sense of pride.” Yvonne’s strength isn’t in never feeling afraid — it’s in showing up, speaking up, and continuing to live with purpose and grace.
Watch Yvonne’s full video to find out more about her experience:
Learn how Yvonne earned her doctorate while navigating treatment.
What she told her doctor when facing her first stem cell transplant.
The surprising support system that helped her graduate during hospitalization.
How CAR T-cell therapy changed her approach to treatment.
Why she believes self-advocacy is the most powerful tool in managing multiple myeloma.
Name: Dr. Yvonne D.
Age at Diagnosis:
52
Diagnosis:
Relapsed/Refractory Multiple Myeloma
Symptoms:
Severe hip pain
Trouble walking (due to a broken pelvis)
Extreme fatigue
Bone pains
Treatments:
Chemotherapy
Stem cell transplant
Radiation therapy
Surgeries
CAR T-cell therapy
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
Thank you to The Leukemia & Lymphoma Society for their partnership. The Leukemia & Lymphoma Society is here for you with information about clinical trials, resources, and support.
One symptom that stood out was the pain in my hip.
Introduction
I’m Yvonne and I was diagnosed with multiple myeloma on August 25, 2008.
My husband and I are retired, so we’re involved with a lot of volunteer organizations. We’re busy with activities at home. We like entertaining, traveling, gardening, and cooking. Outside of illness, we try to expand our interests in different areas. We watch plays and visit museums. We live our everyday lives. It’s about living with the disease and not succumbing to it.
How My Symptoms Started
One symptom that stood out was the pain in my hip. We went to a family reunion and were flying back from Delaware. When I stepped down from the shuttle, this pain exploded. My family got a wheelchair for me. That week, I was in the doctor’s office and the process of getting the diagnosis began.
How My Family Motivated Me
It has been 17 years. My daughter was starting college and I was determined to see her graduate. I have since seen her graduate four times. My family needed me and I needed them. I was determined not to have a defeatist attitude. I wasn’t woeful at the beginning. I never was. I needed to understand what I had and how to navigate this.
They were encouraging and supportive with every treatment. I learned that through illness, you build some resilience. You have to build resilience. I had things to look forward to. I had life to look forward to.
Even though the diagnosis was bleak initially, there have been advances in therapies and I continued to be positive about it. As such, I’ve continued to be involved. I went back to school and did all the things that you do when you’re not thinking about what’s going to happen. I never thought about whether the end was near.
I didn’t share my story with too many people. I was working for an airline at the time. They knew that I was ill. I would go for my treatments and go back to work. I kept one foot in front of the other and went about the business of living and not thinking about the alternative.
I took the resources that were presented to me and continued to learn about the new therapies.
What Resources Helped Me at the Beginning of My Diagnosis
My involvement with Myeloma Link took me into the community as a community volunteer at different events. They were in churches, in sorority and fraternity meetings, explaining what myeloma was and how you should continue to take care of your health. I became involved with another organization as well.
I took the resources that were presented to me and continued to learn about the new therapies. I spoke with my oncology team as well, who helped me through this process.
Materials were available to patients at Emory. I remember picking up a pamphlet. My initial involvement didn’t come until 2018 to 2019, but I had the material and I continued to research and read.
I decided after my stem cell transplant that I needed to become a little bit more engaged with my health as well as the community. I went to a conference, spoke with one of the representatives about volunteering, and the rest is history. I went through some training and shadowed a couple of volunteers.
They froze the cells, but I didn’t receive my stem cell transplant until 10 years later.
How I Found Out About CAR T-cell Therapy
I’ve only had two oncologists. My first doctor retired. He was slated to introduce one of his patients to CAR T-cell therapy. He had discussed this treatment with my family years prior. It was still in the developing stages then.
During a consultation visit, he talked to my husband and me about this new therapy and we agreed to it. We scheduled it after one of my graduations. I pushed it back a little bit because I wanted to walk across the stage, which I did.
I was in the hospital for about a week. I was fine for about two to three years and then I had to go back into treatment. It was explained to me that this treatment is the latest and greatest. I felt fine and still do. I’m back in therapy now getting a different treatment, but I’m nowhere near as ill as I was.
What It Felt Like to Do New Treatment Therapies
The only anxiety that I experienced throughout my experience was getting the stem cell transplant. I was receiving three different drugs twice a week for six months. In week 6 or 7, I went to the hospital to get the stem cell transplant. I reacted positively to the treatment initially. I distinctly remember that my stem cells were extracted on my birthday in 2008.
After all the paperwork and the discussions about how this was going to play out, I was downright scared of this treatment. It was explained that I was going to the hospital and would get a massive dose of chemotherapy. I remember asking my oncologist what this would do. He looked at my blood work and said, “It will get you to where you are now,” where the count was zero and the myeloma count wasn’t showing up. I said, “I don’t want it.”
They froze the cells, but I didn’t receive my stem cell transplant until 10 years later because I reacted so positively to the treatments that were being administered to me. I was happy about that, but that was the only time that I was scared about receiving some form of treatment.
I wanted to prove to myself that, despite all the different moving parts, I can still get this done.
I Earned My Doctorate Before My Second Stem Cell Transplant
It was fulfilling for me to earn my doctorate. It was something that I challenged myself with. At the end of the road, I was going to walk across the stage. I was going to go back to treatment at the same time I was going to graduate. I said, “This is something I want to do. Is that possible?” They said absolutely, so they rescheduled all the preliminary work for about three weeks. I was able to graduate and then go back to the hospital.
I wanted to do that also because when I finished my master’s degree, I was in the hospital. I was going to miss my last two classes. I was in my second-to-last class and I had to go to the hospital. My professor gave me a grade because I had done the work.
She was so instrumental in my graduating with my master’s degree. She came to my house and tutored me for my last class so I’d catch up. I’ve had a support system from the least likely of people, which gave me the drive to survive and say that I could do this.
I graduated with honors in my doctoral degree, and I was proud of myself. My family was proud of me. That speaks to being determined to do your best and not succumbing to the myeloma. Just because I don’t feel well doesn’t mean I’m not going to do this or that. That’s never been how I am. I wanted to prove to myself that, despite all the different moving parts, I can still get this done. And I did.
What I Learned About Life
You move past pettiness. When you’re diagnosed with cancer, you look at the bigger picture and what’s important. You look at what life is about. Sure, there’ll be ups and downs, heartaches, and all the things that one would experience when you’re not afflicted with a disease, but you learn to appreciate the beauty of small things.
I’ve learned to discover what else I can do, how I can help, and how I can give back. When I was at different events with The LLS and the public would come up to the table, I was the example of how you can continue to move through the disease.
Positivity is key. You don’t want to come into this journey with a defeatist attitude.
I was being asked questions, so I shared, but I didn’t go in depth. I let them know that I’m a myeloma patient and have been for X number of years. You can move through it. Not necessarily past it, but you can move through it with a sense of pride. I’m a survivor and I will continue to keep on surviving for as long as I can.
What I Want Other Multiple Myeloma Patients to Know
Remain positive. Be your own advocate. Understand what you’re going through. Ask the tough questions, even if you don’t want to hear the answers. Learn what may be available to you.
Positivity is key. You don’t want to come into this journey with a defeatist attitude. You need to keep your chin up. Strive for something. Appreciate life and its beauty. Love your family. Tell everybody you love that you love them. Live your life.
Thank you to The Leukemia & Lymphoma Society for their partnership. The Leukemia & Lymphoma Society is here for you with information about clinical trials, resources, and support.
Symptom: None; found through blood tests Treatments: Total Therapy Four, carfilzomib + pomalidomide, daratumumab + lenalidomide, CAR T-cell therapy, selinexor-carfilzomib
Why Showing Up Matters: Nat’s Caregiver Role in His Wife’s Muscle-Invasive Bladder Cancer Story
When Nat’s wife, Ebony, was diagnosed with muscle-invasive bladder cancer, life shifted dramatically for their entire family. As Ebony’s primary bladder cancer caregiver, Nat found himself navigating not only the physical demands of caregiving but also the emotional complexities of supporting a fiercely independent woman through something so life-altering.
Interviewed by: Taylor Scheib Edited by: Katrina Villareal
He wasn’t just present for her treatments — he became a constant, steady source of reassurance, encouragement, and strength, even when his own heart was breaking. Early signs were subtle, which included frequent bathroom trips and unexplained abdominal bloating. Ebony brushed them off at first, and like many people, she hesitated to push harder for answers.
When the diagnosis finally came, it hit like a punch. Despite medical appointments and proactive efforts, no one expected bladder cancer. Nat remembers the moment clearly, experiencing shock, disbelief, then anger, but he quickly moved into action mode, determined to be there every step of the way.
Throughout the experience, Nat stayed grounded. He didn’t try to predict the future or let fear take over. Instead, he focused on “conquering the day,” one at a time. His presence at every appointment spoke volumes. Even when words fell short, just showing up was a lifeline. That’s something every bladder cancer caregiver should know: being there matters more than having the right thing to say.
Navigating stigma was another layer of challenge. Bladder cancer isn’t always widely discussed, and Ebony didn’t fit the typical profile. Nat and Ebony leaned on bladder cancer support groups and online communities but were cautious, as too much information sometimes did more harm than good. Nat often had to remind Ebony to unplug from Google and focus on her story, not someone else’s.
Decisions about treatment — chemo, surgery, and eventually a neobladder — were daunting. But they approached everything as a team, asking questions, doing the research, and advocating for the best care possible. As a muscle-invasive bladder cancer caregiver, Nat learned how critical it is to be informed but not overwhelmed, to stay involved without letting fear drive every choice.
Nat and Ebony also had to help their sons understand what was happening without scaring them. That meant honest, age-appropriate conversations and plenty of reassurance. They were careful to preserve a sense of normalcy while allowing space for emotional reactions.
Now, years later, Ebony is doing well, and their relationship is stronger than ever. They celebrate the small milestones, like the first post-surgery walk or a day without pain. Nat says the experience taught him to cherish every moment and let go of the small stuff. He encourages other caregivers to do the same: stay present, speak love often, and make space for joy, even amid hardship.
Name:
Ebony G.
Diagnosis:
Muscle-Invasive Bladder Cancer
Staging:
Stage N2
Symptoms:
Microscopic amount of blood in the urine, which increased to a visible amount of blood
Pain when urinating
Weight gain in the midsection
Treatments:
Chemotherapy
Surgeries: removal of the bladder & bladder reconstruction (neobladder)
Thank you to Johnson & Johnson for supporting our independent patient education content. The Patient Story retains full editorial control.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.
She never lost her beauty. She even became more beautiful after having experienced the ashes of her life.
Introduction
My name is Nat. I’m Ebony’s husband. My wife was diagnosed with muscle-invasive bladder cancer and I was her caregiver during that time. I’m not her caregiver now, but I still provide that support because it is needed even after recovery. I’m a father of three boys and a dedicated husband.
She would probably say that I’m an easygoing person. I don’t go from 0 to 100 easily. She would probably say I have a sense of humor. I’m definitely a jokester. I love to have fun. She’d describe me as pretty easygoing and laid back.
Ebony is a champion. Being there beside her and seeing everything that she had to go through, overcoming the internal challenges of the disease, as well as the external evidence of the disease, which played a big part emotionally and mentally.
She loves her hair and she knew that I loved her hair, so one of her biggest first concerns — and it may sound vain —was losing her hair. I know that played a big part in her daily walk through the cancer experience. She’s always had her hair. Some people don’t care about hair like that, but she did. I knew that was a big challenge for her.
She’s a very independent person, so having to rely on someone to help her do things that she used to do on her own was a big challenge.There were times when she was in the hospital and her heart rate was out of control, but she still needed to walk. She’s a determined individual as well. She could be stubborn, but stubbornness can work to your advantage, too.
In this battle, she was definitely stubborn. She was not going to lie there and die, and not do what needed to be done to become better. When I see her, I see her as a champion, a warrior, someone who overcame, and a good, stubborn person. I see all of those things.
She never lost her beauty. She even became more beautiful after having experienced the ashes of her life. She grew into something different and better.
She started going to the restroom frequently… My antenna started going up a little bit, but I still did not think it was cancer.
How Ebony’s Muscle-Invasive Bladder Cancer Symptoms Started
Initially, she didn’t share with me the symptoms that she was experiencing. Like many of us, when we experience something that isn’t such a huge red flag or shocks us into getting checked, we don’t move, so that’s probably why she didn’t initially. If she did, it was probably very casually done, so it wasn’t alarming.
As time went on, I recall her beginning to share more of her gaining weight in her stomach, which wasn’t an area where she gained weight.
I’m very observant, so I noticed she started going to the restroom frequently. As soon as she came home, she would go to the bathroom immediately. My father had prostate cancer and I saw the frequency and urgency that which he would have to go. My antenna started going up a little bit, but I still did not think it was cancer.
She said, “I’m going to go to the doctor because something is not right. I don’t gain weight here. I frequently have to go to the bathroom.”
Getting to the Diagnosis was Frustrating
It was frustrating for somebody to tell you that nothing is wrong when you know that something is wrong. I can’t diagnose myself. I can’t open my body up to find what’s going on, but I know that something’s going on inside.
When she went to the doctor, she called me and said, “They’re saying it’s just normal. This could just happen with age or being a mother.” You go on with your day because you want to lean into what the medical professionals are telling you. You want to believe that.
The process of getting the diagnosis was a challenge. Then, to get the muscle-invasive bladder cancer diagnosis, suddenly, everything is zoom zoom zoom. As you’re thinking about what’s to come, you’re thinking about what happened.
How did we get here? We checked the boxes. She was going to the doctor. She was seeing the urologist. She was going to the gynecologist. She was doing everything right, yet here we are.
To worry is to have already given an end to a beginning that has never started.
How I Supported Ebony in That Year and a Half to Diagnosis
I try not to think so much ahead. I’m not a worrier, but it’s not because I’m such a strong person. To worry is to have already given an end to a beginning that has never started. I know that if I go into that headspace, then it’s going to cause stress and spill over from that.
I’d say, “You’re good. Everything’s fine. It’s going to work out.” I didn’t have a medical answer, so I could not speak to that. I just had a faith answer that it was all going to work out. You were going to be fine. It wasn’t going to be that bad.
The Moment Everything Changed
When he uttered those words, I could not believe it. I was in a state of disbelief. I looked over at Ebony and instantly saw her eyes. I asked the typical questions: What are we looking at? What’s the next step? What do we need to do? Where do we go from here? How bad is it? You think about all of those things very quickly.
Then I felt a sense of anger because she’s been getting checked, and now this is what they tell us. The doctor just blurted it out.
Ebony was crying, walking out of the doctor’s office. It seemed like the world stood still because you’re trying to process everything. It was not until we pulled into our driveway and I parked the car that I began to cry.
Going through the cancer experience and the healing journey, you have to be careful of the environment that you keep and what you take in.
Nobody wants to hear those words. It was already a delicate time for me. My father had passed away in 2020 and 30 days before him, my older sister had passed. My heart was delicate.
I know I said earlier that I had faith answers for things, but I’m not the individual who does not understand. I’m human and I have human thoughts and emotions. When you hear the word cancer, you automatically think death sentence.
You automatically think, “How much time do I have?” That’s where your mind goes when you’ve had people who have passed away from cancer. After I got over that moment, it was, “This is what we have to do. What’s the schedule? Here we go.” It was time to do that. Now it’s time to compartmentalize because we have things to do to kick this cancer’s behind.
How We Learned More About Bladder Cancer
Bladder cancer was unique to us. We didn’t know anybody to call up and ask. She didn’t fit the mold of what they said a bladder cancer patient should look like, so we didn’t know where to go or who to ask.
My wife is a researcher. She was going to Google. The medical practice gave a manual of support material. The resources they gave her were helpful.
There were support groups that we didn’t even know existed. I found a support group on Facebook that we joined. But because it’s the Internet, you have to be very careful. Going through the cancer experience and the healing journey, you have to be careful of the environment that you keep and what you take in.
You have to be careful what you read and what you process because some people will quickly make it a death sentence. Some people will share with you how they had a friend who had the same sickness and died within two years. It’s not their intent to hurt you, harm you, or make you afraid. Now, because that’s what you see, that’s what you accept, so we had to be careful of that.
There weren’t a lot of options and we didn’t have time to decide what we were going to do.
I had to tell her to put her phone away and say, “Don’t read that today. I don’t need you scrolling through the comments. That may be their reality, but that doesn’t mean that it has to be your reality.”
She’s a very smart person. She’s a chemical engineer, but I have to tell her to stop Googling, “You’re not a doctor, so you may not understand the verbiage that they’re using. It causes extra stress on you that you don’t need for your healing process.” You don’t want to walk in ignorant concerning your diagnosis or what the physicians have told you, but you still have to be careful.
Discussing the Treatment Plan
The options were chemotherapy and surgery. When we got the diagnosis, he said, “It’s very aggressive. We have to start now.” There weren’t a lot of options and we didn’t have time to decide what we were going to do. It was this or that.
She underwent chemotherapy and surgery. There were more options with the type of surgery than for the treatment plan per se. You can get the neobladder that she has or have the bag attached for life, which she definitely did not want. Being in her mid-40s, she was still in her prime. She didn’t want the bag.
I give the team kudos. They were phenomenal. They never made you feel like a burden. They were very empathetic and professional. It made the decision to go with the neobladder, the chemotherapy, and the surgery very easy.
My first concern was, “How does your body function without a bladder?” When I was a kid, all the way up through a portion of high school, I wanted to be a doctor. This was interesting. He’s explaining what it will look like. I’m thinking, “No bladder. That’s not pretty. We need a bladder. You have to have one. How does this happen?”
If you want to support someone as a caregiver, your presence matters.
Then he talked about creating a bladder out of your intestines. I asked him, “Can you not do a bladder transplant? You can transplant hearts, lungs, and kidneys. Can’t you transplant a bladder?” He said, “We’re not there yet, but this is the next best option.”
We researched and were ready to go with it. You’re nervous about it, of course, because if he’s not the only one, he’s one of the very few who specializes in neobladders. I thought it was amazing, but at the same time, it was pretty risky. I was between impressed and scared.
Ebony was pretty calm, but because I know her, I knew she was nervous. She had her questions ready. I don’t think we went into an appointment where she did not have her questions ready. She had the research that she had done on different options. She was nervous, but she never cried. She wanted to get the facts. Whatever she needed to do to survive, she was ready to do that.
How We Continued to Communicate
It wasn’t hard because you have a big elephant in the room that you cannot ignore. You have to talk about it. You have appointments almost five days a week. You may have three appointments in one day. You have to talk about it because it’s not just the two of you. We have children. We have careers. There’s a lot of communication that has to be done for things to keep moving.
As soon as she was notified of an appointment, she would automatically send it to me so I could put it on my calendar. Everything would be scheduled that way. There wasn’t an appointment that she went to that I did not go to, which was very important.
If you want to support someone as a caregiver, your presence matters. Your words may not always matter, but your presence matters, and that was a way of communicating through this experience. Even today, that’s our way of communication.
If you conquer the day, you’ll be okay, and that’s what we continue to do.
Looking Back at Ebony’s Story with The Patient Story
I remember the headspace that she was in. I told her, “You don’t have to worry about that,” and she started saying, “But…” “There are no buts. I’m not going anywhere. You don’t have to worry about that. I’m going to be here. Let that be the least of your concerns.”
Sometimes, she can be stubborn. Here is where you have to watch what you read. She would say, “This person said this,” and I’d tell her, “I’m not that person. You know how I feel about being compared to anybody. I’m not them and we’re not going there, so let’s move on.”
What’s interesting is I didn’t even think about it. Even when we were talking to the nurse and the nurse brought that up, I was not thinking about that. We’ve been together almost 20 years. If you cannot control yourself in moments like this, you have a bigger problem in your marriage.
I even saw some of the comments in her interview where wives were saying their husbands left. My mind did not go there. It doesn’t mean that you are less of a man; that means you’re more of a man because you can now place the need for healing of your spouse over the need for a few moments of pleasure.
You’re trying to have a lifetime of pleasure. You’re trying to have more pleasure in your life with the person you say you love. Surely, I can put that on the back burner and focus on my spouse getting back to a place of wholeness because right now, she’s experiencing some brokenness. That’s where my mind was.
Where We Are at With Survivorship
You would not even know that anything happened. We celebrate the anniversaries, if you will, of that experience because it helps you appreciate where you are.
One of the things that I did right before her surgery was to take her and the family to the beach. She loves the beach and so do I. Being a travel business owner, I researched where we could go. We went to the beach and had an amazing time. I knew it would be a while before we could go anywhere and I knew she was very worried.
We were approaching a surgery that was about to change her life forever. I wanted to do that for her. We continuously celebrate the milestones — the day when she was in the hospital, the time when she couldn’t walk by herself — and that helps that wholeness be there.
Physically, I know she knows and probably thinks within herself that there’s still something different. Her body was not designed this way. She has to self-catheterize. But the wholeness of her emotions and her mental space is what it is. Even when she was concerned about her hair, her hair grew back better than it was before she lost it.
My thing for her was to conquer the day. If you conquer the day, you’ll be okay, and that’s what we continue to do.
The outpouring of support, love, prayers, and gifts was unreal. I believe that made an impression and an impact on our sons to see that we were not in this by ourselves.
How We Told Our Sons
Talk about communication. That was a big piece of communication because you are concerned with how you’re going to tell your children something that they should know without scaring them. Ebony said, “Nat, you tell them because you are good at that. I will probably start crying, but you know how to communicate and bring some assurance to them.”
We brought them all together on the couch. I told them what she had been diagnosed with, what she’s going to experience, and the changes that they’re going to see, such as her hair. But I told them she’s going to be fine. Ebony and I did our very best to make every day as normal as it could be.
The boys’ demeanor is like mine. They’re not going to worry. After we told them, they went on about their day. Sometimes, she would wonder if they’re worrying because teens have a way of not expressing themselves in front of you, but it comes out through other channels.
We think it affected our middle son as far as his studies. We met with his counselor as his grades dropped during that period and we told them what was going on during that time. We needed to communicate with our children and be as prepared as we could for any questions that they had. I told them if they had any questions or felt any type of way, they could ask and talk to me about anything.
The outpouring of support, love, prayers, and gifts was unreal. I believe that made an impression and an impact on our sons to see that we were not in this by ourselves. We had our parents or close friends come and look after them when we couldn’t be here or running around a lot. That’s how we navigated with our sons.
One of our good friends organized a meal train. People were dropping off food for dinner. When she was having chemo, I was at the hospital with her. They were even bringing food for me to the hospital. It was a breath of fresh air. Humanity may not be as bad.
You look at life through a different lens.
How I Was Taking Care of Myself During That Time
Honestly, I don’t think I did anything different. I had to be present and positive. I did have a few moments, but when I did, it was never in front of her or the children. Maybe because I was present, doing what I should do, so I didn’t feel like I needed to do anything extra to take care of myself.
People asked me, “Are you okay?” The wife of a good friend of mine, who was also my pastor back home, was going through cancer at the same time, so he and I would communicate. I remember calling to tell him the news once we made it public. When I shared it with him, we almost had the same story, just different types of cancers.
What Changed in Our Relationship
We enjoy more moments together and life in general. You look at life through a different lens. You don’t start majoring in minor stuff. There’s a saying about protecting your peace. You do adopt that. I am not about to deal with drama and this, that, and the other. I’m about to enjoy my life because you see how quickly life can change.
Just because she went through cancer doesn’t mean that we never disagree. It doesn’t mean that we don’t have arguments. It doesn’t mean that she doesn’t get upset with me and I don’t get upset with her. What it has done is make us not sit there and be angry forever, which I never did anyway. We can’t be doing this. It shifts and changes.
Every loss should make you appreciate the game. Every challenge should make you appreciate overcoming. Every day is a literal blessing to be alive. I tell people that the last four years of my life are one of the hardest periods, which included the losses and Ebony getting diagnosed with cancer. It shifts your thinking.
We now live in a space of living. She loves flowers. If you want to go outside and pick hydrangeas, go ahead and do that. Who cares? Nobody cares. If you want to roll around and frolic in the grass, who cares? As long as you are enjoying the time that you have.
For my birthday, she took me to San Francisco to watch a Golden State Warriors game versus the Lakers. I’m not a Lakers fan, but she took me there. It was amazing. It all speaks to enjoying the moment and enjoying life. That’s what I tell everybody. While you have the time and the opportunity, enjoy life.
I’m a person of faith, so I pray… It will get hard and you want to be there for that person in the best way that you can.
What I Want Caregivers/Partners to Know
Be present and be supportive. Be informed because it’s not a cancer that, from what I’ve seen, has a lot of information out about it. It’s becoming more discussed now than it was a few years ago, but do your best to stay informed.
As a caregiver, be present and remain positive. You’re not living in a space of untruth. Yes, this is your truth. This is the reality, but you have to become selfless as a caregiver. You have to assure that person that you are there for them. No matter how unattractive they may feel they are, they are the most beautiful thing that has ever walked this earth.
When Ebony came out of surgery, she was swollen. Nobody told us she was going to be like that. As I walked in, she had come to and was somewhat alert. She knew it was me. I was taken aback, but I couldn’t show that. You have to become selfless.
I’m a person of faith, so I pray and that is one thing I would definitely say to do. It will get hard and you want to be there for that person in the best way that you can. There were times when she was in the hospital and I couldn’t say anything. All I could do was be there and hold her hand. That was it.
There were times when she was in pain, moaning and groaning throughout the night. She doesn’t even remember that, but I couldn’t do anything. Nothing. That’s how you realize how little we are, when you cannot control the pain or the situation. It was the presence that contributed to her wholeness.
To anyone who is a caregiver to someone with bladder cancer, be a reassuring individual and a force in their life. Things may change, but let them know that you’re not going anywhere and they’re going to be all right. Let them know you’re going to live life to the fullest and conquer the day.
I believe God is always there, even in those moments of fear, doubt, and questioning. You’re never alone.
My Message of Hope
I know that my presence was there with her. I was not the one with cancer. Your friends can love on you, call you, be supportive, and be there for you, but you can still sit there and think, “I’m the only one. They don’t have what I have. They haven’t been diagnosed with what I have. They have a full bladder. I have one that’s been created out of my intestines.”
You may feel alone, even in a crowd. However, you’ve got to know that you’re never alone. There’s somebody who is going through the exact same thing as you or even worse. There were periods when she discovered somebody else who had bladder cancer, but their story was not turning out the way hers was. It made her and me even more appreciative and grateful for it being better than what it could have been.
I believe God is always there, even in those moments of fear, doubt, and questioning. You’re never alone. This may be a stretch for some people, but lean into your peace.Conquering the day is what I told her every day of chemo because she had to lean into that. That brought peace not only to her but to me.
None of us knew what the outcome would be. We hoped for it and prayed for it to be a certain way, but we didn’t know. Guess what? If I’m going to go through this, I can’t go through it spinning out of control. I don’t know what’s going to happen and I can’t put death as my today. We’re just going to conquer this day, this moment.
That’s my message of hope to anyone going through the situation. Conquer the day and you will find out that you’re stronger than you thought you were. There’s a little angel somewhere rooting for you, pushing for you, and clapping their hands like our little son did. He was sitting at the table, then he looked and started clapping because he saw his mom walk with me for the first time without her walker. There’s always an angel somewhere.
The Power of Holly’s Self-Advocacy in Rare Cancer Detection
When Holly started feeling a nagging pressure in her jaw back in 2021, she never imagined it would lead to a diagnosis of stage 1 adenoid cystic carcinoma. The pain was subtle at first, almost like a pinch, but persistent. Like many, she turned to Google. She initially suspected a temporomandibular joint (TMJ) disorder and saw her dentist, but he said it wasn’t and thought it was stiff muscles or tension.
Due to Holly’s history of vertigo and dizziness, she saw her ENT. After a thorough exam, he said it didn’t seem to be anything to worry about. He offered to do a CT scan, but Holly thought it might be an inner ear issue, so she didn’t pursue that path. She even went to see a rheumatologist in case it was an autoimmune issue.
Holly knew something wasn’t right. Her inner voice kept nudging her, so she continued pushing for answers. The rheumatologist suggested that she see a maxillofacial surgeon, who ordered an MRI, revealing a 0.5 mm mass in her parotid gland.
The mass was originally thought of as a lymph node, but Holly pressed forward. She found a specialist who finally offered a needle biopsy, a decision that changed everything. The pathology report came back with the official diagnosis of stage 1 adenoid cystic carcinoma. The news felt overwhelming. Holly had never heard of this rare cancer before.
Researching online only amplified her fears. What stood out most wasn’t the medical terminology, but the realization that many people discover this disease far too late. Holly caught it early, which her surgeon said was almost unheard of, especially given the tumor’s minuscule size.
Surgery followed, but the first attempt missed the tumor. Undeterred, Holly advocated for a second surgery with an ultrasound used in real-time. It worked. The tumor was finally removed and margins were clear.
Because it was stage 1 adenoid cystic carcinoma, her team decided against radiation due to the clean surgical outcome and the harsh side effects of facial radiation. Instead, they began a rigorous scan schedule. She now gets checked every six months, and so far, everything’s been clear.
Through her entire experience, Holly emphasizes one powerful message: self-advocacy is everything. She was persistent. She didn’t doubt the professionals, but she trusted herself, too. Her story is a powerful reminder that knowing your body, trusting your instincts, and refusing to settle for vague answers can make all the difference, especially with a rare diagnosis like stage 1 adenoid cystic carcinoma.
Today, Holly works full-time, volunteers, and spends every possible moment with the people she loves. She’s not taking anything for granted. Her gratitude is real, her perspective is grounded, and her story might just empower someone else to speak up — and speak out — when something feels off.
Watch the full video of Holly’s interview to find out more about her story:
What to do when every doctor says wait and see, but your gut says to keep pushing.
How Holly spotted stage 1 adenoid cystic carcinoma before anyone else even suspected cancer.
Why she chose to skip radiation and what gave her the confidence to say no.
What convinced her to keep advocating when the scans looked “normal.”
Name: Holly A.
Age at Diagnosis:
49
Diagnosis:
Adenoid Cystic Carcinoma
Staging:
Stage 1
Symptom:
Persistent jaw pain
Treatment:
Surgeries: two parotidectomies (second with intraoperative ultrasound guidance)
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
Symptoms: Sore on the tongue, which caused pain during eating and speaking; changes in the color and texture of the tissue where the sore was located Treatments: Surgery (partial glossectomy, radical neck dissection, reconstruction), radiation ...
Jackson’s Stage 3 Colon Cancer at 26: Difficult Days While Trying to Keep a Routine
When Jackson was diagnosed with stage 3 colon cancer, right before his 26th birthday, it came out of nowhere. He had only been experiencing abdominal pain for a couple of weeks, which led to a trip to the ER for dehydration, only to discover something far more serious. The shock of hearing “colon cancer” at such a young age was overwhelming, especially with no family history and no warning signs.
What followed was a whirlwind: emergency scans, a colonoscopy, a biopsy, and a surgery all within days. Even before the official diagnosis of stage 3 colon cancer, Jackson had already undergone a transverse colectomy. It was fast, intense, and life-changing. But through it all, Jackson found strength he didn’t know he had.
There’s been a concerning rise in colon cancer in young adults, and Jackson’s experience highlights why awareness and timely attention to symptoms, no matter how seemingly minor, are critical. At an age when most people are focused on careers and relationships, Jackson was juggling chemotherapy with prepping for the bar exam. Instead of slowing down, he pushed through with grace, humor, and a lot of grit.
What stood out most in Jackson’s story is his mindset. He didn’t sugarcoat the hard days — like the allergic reactions to chemo, the side effects that made him feel decades older, or the anxiety of waiting for scan results — but he emphasized the power of keeping a routine, doing “normal” things with friends, and finding ways to enjoy life even during treatment. Reclaiming small parts of normalcy helped him feel human again.
Jackson also credits a lot of his resilience to his support system: his fiancé, family, friends, and coworkers, who helped keep him grounded and encouraged. Their presence gave him something to lean on during the hardest moments. Jackson wants others facing stage 3 colon cancer to know that they’re never truly alone.
Today, Jackson’s cancer-free, grateful, and looking forward to all the parts of life that once felt uncertain. His message? Believe you can get through it. Lean on people. Stay hopeful. Live your life. And never be afraid to speak up when something feels off.
Watch Jackson’s interview to find out more about his story:
How Jackson didn’t let cancer stop him, even if he was diagnosed with stage 3 colon cancer just before taking the bar exam.
How he found hope, balance, and even joy in the middle of treatment.
How subtle symptoms led to a life-changing diagnosis.
From chemo infusions to hanging out with friends, Jackson made living through cancer feel possible.
How he used mindset, support, and routines to power through cancer treatment.
Name: Jackson A.
Age at Diagnosis:
25
Diagnosis:
Colon Cancer
Staging:
Stage 3
Symptom:
Sharp abdominal pain
Treatment:
Surgery: emergency transverse colectomy
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
Treatments: Chemotherapy, surgery (installation of port and liver infusion pump, colectomy, hepatectomy, liver ablation, removal of liver infusion pump)
Advancements in Metastatic Breast Cancer Treatment & What They Mean for You
Abigail Johnston was a successful lawyer and mother of two young children, living a fulfilling life before being diagnosed with stage 4 metastatic breast cancer in 2017. Her diagnosis, with a prognosis of just 12 to 36 months, was devastating, but she chose to take an aggressive approach to treatment.
Abigail shares the emotional toll of her diagnosis, how she focused on being present with her family by closing down her law practice, and then highlights the power of how understanding more about her disease would change her life, specifically in understanding her cancer biomarkers.
As she reflects on the incredible advancements in metastatic breast cancer treatments and the hope she holds for long-term survival, she brings in another top expert voice, breast cancer specialist, Dr. Neil Vasan from Columbia University, to discuss the latest updates from the largest breast cancer meeting in the world, San Antonio Breast Cancer Symposium.
They talk about the most promising treatments that may be close to FDA approval, how getting tests to understand your disease can completely change your life, and even how the weight loss drugs like GLP-1s have entered the conversation in breast cancer.
Thank you to Pfizer for supporting our independent patient education content. The Patient Story retains full editorial control.
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.
Some live for 15, 20, and even 25 years with stage 4 metastatic breast cancer.
Introduction
Abigail Johnston: I have been living with stage 4 metastatic breast cancer. At the age of 38, I was told I had 12 to 36 months to live. As a young person in the middle of my career with two young children, hearing that was devastating and overwhelming.
I chose to be more aggressive and have my treatments happen in a certain way because I’m always thinking of being present with them. I closed my law practice about a week after my diagnosis because if I was going to have limited time, I wanted to spend all that time possible with my kids and not in the office. I count those times with my kids and my husband as so much more valuable.
Some live for 15, 20, and even 25 years with stage 4 metastatic breast cancer. We need to understand why they live for a very long time. Is it a particular medicine? Is it a particular biomarker? Is it something about their genetics? That’s where precision medicine comes in.
Dr. Neil Vasan: Breast cancer is multiple diseases. It can be estrogen receptor-positive, triple-negative, and HER2-positive. This discussion is for women and patients with metastatic breast cancer, but of course, we have a lot of advancements happening in the curative breast cancer setting.
We think about screening and genetic mutations, and the advances there, which straddle all types of breast cancer. Especially for this audience, three important trials were either initially presented or updates were presented at the 2024 San Antonio Breast Cancer Symposium.
According to the National Cancer Institute: “Clinical trials test new ways to find, prevent, and treat cancer. They also help doctors improve the quality of life for people with cancer by testing ways to manage the side effects of cancer and its treatment.”
For a lot of metastatic trials in the past, we have used tissue biopsy, which is obviously more invasive and takes time to analyze. This trial utilized liquid biopsies in approximately 93% of patients, which was remarkably high. It also enabled this trial to report results quickly.
Dr. Vasan
INAVO120 Clinical Trial
Dr. Vasan: The first clinical trial is INAVO120, which is a trial testing PI3 kinase inhibitors in the first-line setting in women who have progressed on adjuvant endocrine therapy. Thankfully, this is very rare, but we do see it. We do know that there are women who only get one or two years of mileage out of these therapies. Sometimes, these therapies can just stop working. This is a hard discussion with patients because the therapies that we think are supposed to cure you didn’t work.
This was a trial that looked at a type of drug that we give in the later line setting of breast cancer. This is called a PI3 kinase inhibitor. This is based on the fact that 40% of breast cancers have mutations in PIK3CA, which is the main engine of this pathway.
What was interesting about this trial was that they investigated this drug in combination with palbociclib, a CDK4 and CDK6 inhibitor, and fulvestrant in women who had either progressed on adjuvant endocrine therapy or progressed one year with infection. This patient population has very resistant disease.
There are a couple of interesting things about this trial. When this trial was initially reported, it doubled progression-free survival. Very recently, we had a press release stating that it improved overall survival. We don’t yet know the numbers for the overall survival improvement, but this is a significant achievement in the field. It’s the first time for a PI3 kinase pathway inhibitor to have improved overall survival in metastatic breast cancer, so that is a huge deal.
We’ve had drugs like everolimus that have targeted this pathway for decades, but we’re only now starting to see the fruits of that. The reason why overall survival has improved is because of a combination of factors. First of all, we’re using this drug in the first-line setting, so we’re putting all the weapons in one go in trying to eradicate breast cancer.
Second, we, as a field, have made a lot of progress in monitoring toxicities and making sure that these therapies have manageable toxicities. That was another important part of this trial. It was a drug that’s better tolerated than alpelisib, which is FDA-approved.
Lastly, this trial enrolled quite quickly because it used liquid biopsies. For a lot of metastatic trials in the past, we have used tissue biopsy, which is obviously more invasive and takes time to analyze. This trial utilized liquid biopsies in approximately 93% of patients, which was remarkably high. It also enabled this trial to report results quickly.
Some of the things I’ve mentioned have to do with the science, but some of them have to do with implementation issues and toxicities, which are science as well, but in a different way. All of these variables matter. This trial is practice-changing and I’m looking forward to hearing about the overall survival data.
Editor’s Note: This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.
EMBER-3 Clinical Trial
Dr. Vasan: The second trial was looking at a drug called an oral selective estrogen receptor degrader (SERD). The EMBER-3 trial was investigating a drug called imlunestrant, which is sort of an oral version of fulvestrant that degrades the estrogen receptor. There’s already an FDA-approved drug called elacestrant, which is for women whose breast cancers have mutations in the estrogen receptor or in a gene called ESR1.
We see these mutations in about 15 to 20% of patients. I would say that number is a little bit all over the place if you look at the literature. We know that this mutation arises because it is a drug-resistant mutation to aromatase inhibitors. Women whose breast cancers progressed on adjuvant aromatase inhibitors often can get this mutation.
Imlunestrant was tested in combination with abemaciclib or a CDK4/6 inhibitor. This was a trial that looked at a complicated trial, but the gist is that in women whose breast cancers harbored an ESR1 mutation, those women had a longer progression-free survival if they took imlunestrant versus an endocrine therapy of their physician’s choice, which might be fulvestrant or an aromatase inhibitor monotherapy.
There were other more complicated arms of the trial where they looked at the combination of imlunestrant and abemaciclib in patients who had progressed on CDK4/6 inhibitors in the second line. Those resulted in positive data. They had improved progression-free survival. I’m not going to delve into the details of that because, honestly — and I say this as a breast oncologist — it’s challenging to understand exactly. The comparator arms were not necessarily what we would use in the second-line setting.
For any average patient in the second-line setting, we would obtain their genomics, figure out the exact targeted therapy, and then give them that therapy. This trial did not test that particular question. It showed that this combination has efficacy, but it’s hard to understand who the right patient population is. I look forward to seeing how the FDA weighs in on the combination. I anticipate that imlunestrant as a monotherapy is going to be a drug that we see being approved.
I was impressed by the imlunestrant side effect data. If this drug gets approved, I think it will be the preferred drug compared to elacestrant. The reason I say that is not because of the efficacy data, because the efficacy was pretty similar across both trials. It’s more because of the toxicities.
Elacestrant is a drug we give in the clinic. The nausea is very real for these patients. Imlunestrant looks like a cleaner drug. That being said, with all of these drugs, we don’t know how they work until they get deployed in the real world. That’s where a lot of you are very helpful. You can raise awareness for certain types of side effects that we either know about or may not get a lot of publicity, but then in later years, we find out that it’s a big deal.
An example of that side effect is inflammation of the lungs from CDK4/6 inhibitors. That was something that didn’t bear out in the phase 3 clinical trials, but it was patient advocates who noticed these side effects. Oncologists noticed these side effects in small numbers. The FDA did a big analysis where they pooled all of this data together and found out that this was actually a safety signal. This is where you all can be very helpful, as these drugs get newly launched into the real world to help us figure out the toxicities.
PATINA Clinical Trial
Dr. Vasan: The third trial is PATINA, which is an exciting trial and speaks to the fast-moving pace of this field. This hasn’t been published yet, but it is amazing and groundbreaking. The science is one part of it, but the dissemination of the information is another very important part.
Again, this is where patients can advocate. You want these data as soon as possible. Oncologists have already started to implement these results into clinical practice before the paper has been published.
This trial looked at women with HER2-positive metastatic breast cancer who are also ER-positive. HER2-positive breast cancer comprises about 20% of breast cancer and about 70 to 80% of that 20% is estrogen receptor-positive. We sometimes call this triple positive. Generally, we treat these cancers as we treat the HER2 component and then we tack on hormonal therapies in the adjuvant setting and metastatic setting as well.
This trial investigated the addition of CDK4/6 inhibitors, which we know improve overall survival in estrogen receptor-positive, HER2-negative metastatic breast cancer. What about testing it in estrogen receptor-positive, HER2-positive metastatic breast cancer?
It’s a little more complicated because the therapy is a combination of chemotherapy (paclitaxel or docetaxel) with anti-HER2 antibodies trastuzumab and pertuzumab. This is the THP regimen, which is the CLEOPATRA trial. It has been our standard of care for many years now and improves overall survival. It’s the best combination we have in this disease.
They gave the THP therapy. Normally, we give chemotherapy for six cycles, stop chemotherapy, and then patients will be on just trastuzumab and pertuzumab. That’s a great moment in any patient’s disease trajectory and treatment trajectory because once they’re off chemo, the HP (trastuzumab and pertuzumab) has very very few to no side effects.
Patients tell me it’s like getting water. Again, not to minimize anyone who’s had side effects from these drugs, but in large populations, they’re very well tolerated. At that point where we would normally drop the chemo, we would oftentimes add hormone therapy in these patients who are ER-positive, so also adding a CDK4/6 inhibitor, adding palbociclib.
They found that when they did that versus without adding palbociclib, the progression-free survival improvement was gigantic. It went from 29 months to 44 months. One chestnut about this data, if anything, that makes this underappreciated or underrated is the delta or the change between the therapy arms.
You want a big delta. That shows your therapy works. The delta of 12 months is higher than the delta in progression-free survival in ER-positive metastatic breast cancer, meaning that the addition of the CDK4/6 inhibitor is, by these data, maybe even doing more than what we thought it was doing in ER-positive, HER2-negative breast cancer, where CDK4/6 inhibitors transform the landscape.
This is exciting from a therapy point of view. I hope with all my heart that this results in an overall survival improvement. We still need to see, but this is exciting. I think the data blew everyone out of the water. When the progression-free survival curves were shown, there were audible gasps in the audience. We don’t get moments like that a lot and that’s wonderful, so I’m excited about this data.
Taking a big step back, the way that they conducted this trial was interesting because there are other targeted therapies that we use in ER-positive breast cancer, like Akt inhibitors and PI3 kinase inhibitors. PIK3CA is mutated in HER2-positive breast cancer in about 40% of women. Unfortunately, we already know that the antibodies don’t do very well in PIK3CA mutant cancers; antibody-drug conjugates (ADCs) seem to do better.
This is an interesting area to start putting in some of these targeted therapies that we only give in ER-positive breast cancer into the ER-positive, HER2-positive space. We’re going to see a lot more trials doing this paradigm.
That’s something for patients who may have ER-positive, HER2-positive metastatic breast cancer. This is going to be a very fast-moving area. We’re going to see a lot of trials by many companies and even cooperative groups combining all of these therapies.
There’s still a lot of complexity because you could imagine, this is now going from three drugs to four or five drugs. We have to think about toxicity, but this is incredible data. I was floored when I saw this because I was not expecting it as well. Again, that’s wonderful for all of you.
That’s an interesting example where these important questions that you raise, Abigail, form the hypotheses for clinical trials that are tested rigorously and prospectively, which can help change or guide future treatments.
Abigail: In that context, we know this information, but nothing’s been published yet. Is that correct?
Dr. Vasan: Nothing’s been published yet. Many of us have already started to change our recommendations based on this. Of course, this is a conversation with patients. We have an initial glimpse into the data, but we don’t have all the answers right now. This is such an amazing improvement. We hope that insurance companies and oncologists will advocate for you to try to get this and work their hardest to get this drug if this applies to you. Again, this speaks to the fast-moving nature of this field and how it’s so imperative that we get these results out as soon as we can for everyone.
Abigail: We talk about lines of treatment and how, with each line of treatment, usually you can’t go back once you’ve been on a line of treatment. When we talk about these combinations, is there a concern that we’re potentially taking up two lines of treatment in these triplets? What are your thoughts on that?
Dr. Vasan: Our thoughts on that have evolved. There were discussions five years ago about whether patients whose disease progresses after a CDK4/6 inhibitor in the first-line setting should switch to two different therapies, or if we should keep the CDK4/6 on and change the endocrine therapy, or vice versa. These are studies that have been reported.
We know now that switching the CDK4/6 inhibitor in the second line in large populations of women improves progression-free survival. That’s an interesting example where these important questions that you raise, Abigail, form the hypotheses for clinical trials that are tested rigorously and prospectively, which can help change or guide future treatments.
I do think it’s an important question. With INAVO120, this triplet regimen, you’re using three good drugs all in the beginning. There’s clearly going to be more toxicity, which is also something that has to be dealt with. But is that the best thing to do for these patients? I would argue that the overall survival is positive. We don’t know what the numbers are yet, but that’s a great sign and rationale for why you would want to give all of those drugs.
These are the academic discussions we have as oncologists and with patients as well. Sometimes, there are discussions about adjuvant CDK4/6 inhibitors. We know that these drugs improve disease-free survival. They prevent breast cancer from coming back, but we don’t know if they improve overall survival. They may, but it’s possible that they may not. The trials were not necessarily powered to answer that question. They were smaller trials, so we don’t know.
Should we offer this drug or give this drug? Offering versus giving in shared decision-making are two different issues. Should we be offering this drug to all women who meet these criteria? We don’t know if it helps them live longer. These are questions that we wrestle with every day.
For this triplet therapy, the fact that it improves overall survival is a great win for patients. It’s a complex decision because it adds more side effects in the first-line setting. Normally, patients in the first-line setting are not used to having lots of side effects in general.
Abigail: Thank you for that overview. It can be a little complicated for patients to look at these statistical analyses and graphs. They’re a little Greek to those of us who don’t have that background, so it’s always good to have a doctor interpret. It’s also important to see the evolution of science. We know what we know today, but we’re going to know more tomorrow because of clinical trials and ongoing research.
The Impact of Antibody-Drug Conjugates (ADCs)
Abigail: You mentioned ADCs. There were some conversations about antibody-drug conjugates and sequencing.
Dr. Vasan: Antibody-drug conjugates have changed the landscape in the treatment of breast cancer. We now have antibody-drug conjugates that are approved in all three subtypes of breast cancer. For HER2-positive, we have trastuzumab emtansine (TDM1) and trastuzumab deruxtecan (T-DXd). For HER2-positive and triple-negative breast cancer, we have sacituzumab.
For HER2-low, which was triple-negative/ER-positive but HER2-low, we have trastuzumab deruxtecan (T-DXd). For ER-positive metastatic breast cancer, we have sacituzumab and datopotamab deruxtecan (Dato-DXd), which is like sacituzumab, a similar target in ER-positive metastatic breast cancer.
In my opinion, it’s always good to have options on the table. I applaud the FDA. As an oncologist, given the data that that’s been shown so far, it’s hard for me to imagine for estrogen receptor-positive metastatic breast cancer recommending Dato-DXd over sacituzumab. This is my opinion, but it is an option, and it may be the best option for you.
It will be interesting to see how it’s progressed in other breast cancer subtypes and triple-negative breast cancer. It’s being investigated in lung cancer as well. ADCs are here to stay. They’ve changed how we think about drugs and targets. I think about it like next-generation chemotherapy, which is how I communicate it with patients as well.
From my point of view, it’s a helpful metaphor for a couple of reasons. These drugs have side effects that are more similar to chemotherapy. I would argue they’re more muted but similar. And they’re similar in genre. They can cause hair loss, diarrhea, and neuropathy, which are side effects we associate with chemotherapy. Generally, they’re less than what we see with chemotherapy. These drugs are also given in cycles, the same lingo and parlance as chemotherapy. For that purpose, it’s a helpful metaphor.
In the trials testing these drugs, they’re always comparing them to chemotherapy of the physician’s choice. It’s always a head-to-head versus chemo. We’re now seeing T-DXd moving earlier into the neoadjuvant setting and in the ER-positive metastatic breast cancer space. There was an approval for HER2 ultra-low, but it’s moving up.
It’s very likely that soon, with the INAVO120 regimen, if it stops working for those patients, we may be talking about ADCs even in the second-line. These would be patients who are fit and able to tolerate these therapies. That’s a different discussion, but I think that’s where the puck is heading, into the second line. It’s going to be an option. Maybe not for everyone, but it will be an option.
ADCs are changing the game because they’re changing the way we think about toxicity and efficacy, and they’re moving up. More options are always better for patients, but it’s going to be a complicated landscape.
Improving How to Get Medicine to People
Abigail: You’ve talked about toxicities, which is mostly in the context of side effects. What about time toxicity? How do you talk about that with your patients? For example, the difference between taking an oral therapy at home versus going to the infusion center every three weeks for an ADC.
Dr. Vasan: In the HER2-positive metastatic breast cancer space, there has been a lot of emphasis and research on subcutaneous formulations. PHESGO (pertuzumab, trastuzumab, and hyaluronidase-zzxf ) is the drug I’m thinking of, which is given in a shot in the fat. Biosimilars are also a relevant part of the conversation because of cost.
Most of the time, the trastuzumab and pertuzumab that we’re giving in big academic centers are biosimilars now because they’re generic drugs, cheaper, and better for the system. But I do think that this emphasis on the drug getting approved and becoming generic, but with a new formulation, is a very relevant conversation.
This is where your input is very helpful as patients and patient advocates. There may be a world in the distant future where patients, even with metastatic disease, might be taking these drugs at home. I do think that’s a possibility. During the COVID pandemic, when coming into the infusion center was risky for so many patients, those were options that were deployed in trials or feasibility studies. We know it’s possible, feasible, and safe.
Again, this is an area where the puck is moving. Can we come up with better models of getting drugs to patients? The concept of coming in every three weeks versus taking a drug every day have pros and cons. Obviously, a pro about taking an oral pill is that it’s in your control as a patient. You’re taking the medication. It doesn’t necessarily mean that the drug is less toxic. I would argue we have plenty of oral drugs that are more toxic than certain IV chemotherapies. It’s apples versus oranges.
This is where oral SERDs are interesting drugs. We give fulvestrant. Many patients tell us that no one wants to get shots in the buttocks every month. Interestingly, oral SERDs have come along. We thought as a field that oral SERDs were going to replace fulvestrant, but that’s not what we’re seeing because they only seem to have activity in patients whose breast cancers have ESR1 mutations, which is a small piece of the pie.
With every conversation around changing formulations, you have to reinvestigate these questions because some of our assumptions turn out to be wrong. This is an important change in the field. I would even go a step further. Breast cancer has led this in oncology because now we’re starting to see subcutaneous formulations of other antibodies.
These are the things where patients need to be savvy and know everything about what’s going on. If that’s something that gives you solace and lessens your anxiety, these are questions to ask your oncologist. What are the drugs available to me? What are the targeted therapies, antibody-drug conjugates, chemotherapies, antibody therapies, and clinical trials? Which of these drugs are given intravenously? Can we give this in a way that makes more sense for my life? These are all important questions that you should feel empowered to ask because we do have answers.
Abigail: Thank you for bringing up quality of life type discussions and how important it is to have with your doctor.
With obesity, we know that it is a known risk factor for estrogen receptor-positive breast cancer, but less so for other breast cancer subtypes.
Addressing Obesity in the Context of Breast Cancer
Abigail: There was some data that came out at San Antonio about obesity, which is always a sensitive or complicated subject to talk about. How are you having that conversation with your patients, Dr. Vasan?
Dr. Vasan: I’m sure you are aware of the prior Surgeon General’s declaration about multiple cancer types being linked to alcohol intake, and this is important. We’re always interested in trying to find out if there are modifiable risk factors that can decrease the risk of cancer. We know that the warnings on cigarette packs have decreased the rates of lung cancer and the smoking rates are much lower now than they were 20 years ago. But are there other modifiable risk factors that can decrease the risk of breast cancer?
I mentioned obesity in line with alcohol because those two are a little linked. The National Academies of Sciences, Engineering, and Medicine (NASEM) released a concurrent report that argues that if you look at alcohol in the absence of obesity, the risk of breast cancer is a lot lower than we thought. It’s 1% over someone’s lifetime, which is the absolute increase in risk. The relative risk, of course, is higher.
The bottom line is it’s a hard discussion. If there’s a 1% increase in absolute risk, how are you going to decrease that by alcohol cessation, which can be hard and complicated for people? I put that out there.
With obesity, we know that it is a known risk factor for estrogen receptor-positive breast cancer, but less so for other breast cancer subtypes. The way that I talk about it with patients is that this is a modifiable risk factor. If you’re on some sort of active therapy, we’ll put it out on the table and talk about this issue, but we won’t intervene until you’re done with the hardest parts of therapy.
This is something that comes up all the time in the adjuvant setting. It’s natural for women to want to lose weight. You get ambushed with breast cancer, so you want to investigate all the avenues of your life. How can I do better? How can I change things? I always say to patients, “Let’s get through the hardest part. Let’s get through chemotherapy. Let’s get through surgery first. Then, let’s talk about these issues.”
We are starting to see changes in the world of GLP-1s. There’s a lot of interesting work being done looking at these drugs and their anti-cancer effects. These are anti-cancer effects regardless of their effects on diet and weight loss, which is fascinating as well.
This is a fast-moving space. What I recommend to patients is that when we’re talking about weight loss, talk about the real specifics of an exercise regimen and food intake. These are great conversations that are happening in your doctor’s office. This is also something we’re seeing at the national level, even politically. We’re seeing a lot more discussion about lifestyle and changes that can be made.
There’s a lot more awareness now, even in the last couple of years, about what we’re putting into our bodies and our kids’ bodies. The big question is trying to understand if making a change affects your risk of breast cancer. Does that improve your survival with metastatic breast cancer? These are all questions that we’re hoping to find answers to.
They’re very hard studies to design. Certainly, weight loss is going to help anyone, myself included, with all aspects of life: cardiovascular disease, cardiovascular risk factors, etc. But I don’t want someone to become a vegetarian overnight. That’s a pretty drastic change. What’s that going to give you at the end of the day?
These are all important conversations to have, but I do think we’re going to start to see more research done in this area.
Abigail: It’s so important for patients to remember that this isn’t about patient shaming. It isn’t about saying that they’re responsible for anything, but about looking at how to improve the quality of life while reducing risk at the same time. I just wanted to make sure we talked about that.
Editor’s Note: This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make treatment decisions.
The Importance of Understanding Side Effects
Abigail: You were part of a discussion about a case-based clinical approach to ER-positive metastatic breast cancer at one of your presentations in San Antonio. Would you like to talk about that?
Dr. Vasan: ER-positive metastatic breast cancer is a fast-moving field with a lot of new therapies approved within the last two years and with new things in the pipeline. We get into a lot of clinical scenarios. This is very common and happens all the time in the clinic.
Patients who have multiple alterations that we have targetable drugs for, patients who have unusual comorbidities — these are scenarios we see all the time. We’re trying to understand what the best drug is for this patient that will help them live the longest and have the best quality of life. This was a great discussion. It’s wonderful to have a patient advocate on the panel. This is important because a lot of these drugs have side effects that mean different things to different people.
Side effects mean different things to different people. They also mean different things, I would argue, for oncologists compared to patients. The way that we grade and rate side effects can mean a lot of different things. Grade 3 diarrhea is 10 episodes a day, which is insane. Grade 3 is usually the red flag, but grade 1 and grade 2 is still a lot of diarrhea.
Stomatitis is something I think about a lot. It’s a side effect that we’re starting to see more now with Akt inhibitors. There was a reasonable percentage of women who had grade 3 stomatitis, which is inflammation of the mouth. Grade 3 means that stomatitis is so bad that you’re losing weight. Grade 1 means it’s there and grade 2 means it’s painful.
Those are big side effects. You could argue that grade 3 side effect X might be very different from grade 1 side effect Y, if Y is bad. The toxicities and communication of the toxicities are so important to make sure that everyone is on the same page. If you’re having a side effect that you feel is not getting the time that you need to talk about it, you need to talk about it. I always tell my patients, “If something doesn’t feel right, I want to hear from you. I’d rather hear from you than not hear from you.” These are important discussions.
The Importance of Sharing Side Effects with Your Doctor
Abigail: Patients talk about their fear of bringing up a side effect that they’re struggling with because it might mean they can’t stay on the medication. How do you handle that in the clinic?
Dr. Vasan: I always try to make it clear that we have a lot of doses that we can give of drugs. They’re generally for targeted therapies. Patients have multiple options. One of the biggest challenges is trying to communicate that there is no one optimal dose. For whatever reason that we don’t understand, some doses are much better tolerated than others. Certain doses for certain individuals are the perfect range.
It’s very hard to understand and hard to accept. If your doctor recommends a dose reduction, do not equate that with not being as hard enough on yourself or not being as strong. I always tell patients, “I don’t want you to feel the side effects of the therapy. The goal is to see it working on the scans and not have any side effects. That’s not what this is about.”
It’s hard. If I were a patient, I could understand feeling less than if my doctor said I need a lower dose. But I want patients to understand that there’s been so much rigorous analysis of every one of these FDA-approved drugs, looking at lower dose levels, and trying to understand if you are attenuating if you lower the dose. Are you decreasing the benefits of survival, the response rate, etc.? The answer for the vast majority is you’re not, which is so important for patients to understand.
There are a lot of initiatives being done at the American Society of Clinical Oncology (ASCO) level and the Patient-Centered Outcomes Research Institute (PCORI), looking at CDK4/6 inhibitors and changes in doses. Some of these drugs — but not all — are approved in the adjuvant setting. A big reason for that is that some doses were modified, and they used a lower dose in the adjuvant setting.
I want patients to know that doctors are always thinking about this, but that’s a perfect example where it’s baked into how we give the drug. With CDK4/6 inhibitors, we give them three weeks on, one week off. It’s not dose reduction per se — it’s dose intensity — but it’s the same idea. People need to know that if your doctor recommends a lower dose, it’s not because of anything you did or did not do; it’s just because that dose is the right dose for you.
There are a lot of people doing research into pharmacogenomics. There are aspects about different races that may change the way that you metabolize drugs. It’s been known for a very long time that Asians have certain metabolic enzymes that change the way their bodies process capecitabine.
That’s something in the GI (gastrointestinal) cancer field and in certain types of GI cancers, like stomach cancer, that are very prevalent in Asian countries. These are important parts of the conversation. There are biological reasons that we may not know yet that could explain why this dose is not the right dose.
Abigail: Yet another reason why diversity in clinical trials is so important. If we don’t have enough of each group of people, we’re not going to necessarily know if something is specific to that group. Thank you for raising that.
What are You Most Excited About in Breast Cancer Research & Development?
Abigail: What is new and exciting that you’re looking forward to?
Dr. Vasan: I’m very excited about the three trials that I talked about earlier. I think in HER2-positive, T-DXd has already changed the world. There are still many more scenarios that I think T-DXd will find an approved role in. Moving drugs into the neoadjuvant adjuvant setting is always wonderful and I think that’s going to be where that field heads.
The PATINA trial, where we’re starting to integrate targeted therapies into that complicated regimen, is going to be an interesting move that the field heads into.
In estrogen receptor-positive breast cancer, there are still a lot more interesting targets that are being investigated in phase 1 trials. One target I have my eye on is something called KAT6A, an epigenetic target. It’s the idea that your DNA can get modified in lots of different ways. The proteins that modify that DNA are called epigenetic proteins, writers, and erasers. There are lots of different classes and one of those is the protein called KAT6A. It’s going through clinical trials right now. The response rates are very high for patients who have progressed on lots of different therapies. There is also a lot of toxicity, so those will have to be managed.
Mutant-selective PI3 kinase inhibitors are exciting drugs. They seem to have little to no hyperglycemia. They are mutant-selective, so they’re ultra-targeted in a way. They’re only targeting the mutated PI3 kinase in cancer cells and not targeting the normal PI3 kinase in all the other cells in your body, like the liver and fat cells, which can cause all these bad side effects.
Triple-negative breast cancer is still the hardest disease. I do think that some interesting advances are being made in optimizing chemotherapies with immunotherapy. I don’t think we’ve quite cracked that yet. There’s always work being done with BRCA and trying to find the patients who benefit from those therapies.
I think ADCs are going to find a huge traction in TNBC, as they already have. As an example, sacituzumab is a better drug in triple-negative breast cancer than it is in ER-positive breast cancer. There’s still more to be seen there.
I love talking to people who know a lot about breast cancer and people who are outside the field because it’s such a fast-moving field. It’s a privilege to take care of patients who have breast cancer and to be able to talk about all these therapies and communicate. I hope you can tell how excited I am when I talk about this. It’s such an amazing field because everyone is so united and mission-oriented to keep moving faster.
Dr. Vasan: We were inspired by the lung cancer patient advocacy group. There have been targeted therapies for decades now against a slew of genes that are mutated in lung cancer. There have been these incredible groups that have formed around the target. EGFR Resisters is one of them. These amazing groups have changed the world. They have changed patient advocacy. They changed how oncologists think about designing trials. The people in these organizations have seats at the table with pharma companies as they design their trials with regulatory agencies as they’re approving these drugs. It’s incredible.
Breast cancer doesn’t necessarily have a genomically-directed targeted therapy, i.e., a gene that’s mutated that we find on a sequencing report, until PI3 kinase. That’s something that’s lacking in the field.
Abigail and I, together with two other incredible patient advocates, Marlena Murphy, who unfortunately passed away in 2024, and Melanie Sisk, have formed an organization called PIK3CA Pathbreakers. We’re a patient advocacy group formed around patients with PIK3CA-altered breast cancers.
We now have three FDA-approved drugs, two in the last year and a half for this patient population. We’re invested in trying to increase awareness around clinical trials in this space, increase knowledge about side effects through the lens of patients but articulated by oncologists, and try to make sure that we have strategies to mitigate these side effects.
What’s Exciting About Next-Generation Sequencing (NGS)?
Dr. Vasan: The education and landscape around next-generation sequencing have changed dramatically in the last two years. When to get sequencing? What to get sequencing on? How often to get sequencing? These areas are very fast-moving. We’re still trying to make sure that insurance companies are approving these drugs. I do think that these are bigger conversations that we need to have at a national level, but that’s another big area.
What are the mutations? There are thousands of mutations seen in patients. Some are very common, but we get questions all the time about these rare mutations. Do these rare mutations predict response to these drugs? We don’t know.
As an oncologist and someone who specializes in PI3 kinase, I get emails all the time from oncologists all over the country. They see this rare mutation. Does this predict the response for capivasertib? We don’t know.
What are Your Recommended Patient Resources?
Abigail: Thank you, Dr. Vasan, for your time, your insights, and your excitement. As a patient, it’s always good to see that there are doctors, researchers, and clinicians as invested in our care as we think everybody should be. Very much appreciated. The Patient Story has a YouTube channel with all these videos, which is wonderful. But, Dr. Vasan, where do you point patients to get more information?
Dr. Vasan: Every patient is so different. Sometimes you find something online that’s not right or relevant. Sometimes I hear from patients, “I saw this,” and I have to tell them, “That’s not relevant for you because of X, Y, and Z. It might be something we talk about later, but now, this is why it’s not relevant.”
There can be a lot of information and it’s hard to know how to interpret the data. Breast cancer is such a fast-moving field. When anyone gets diagnosed, they’re going to talk to family members. More often than not, how breast cancer was treated in your loved one five years ago might be radically different. It might not even be an option now because there are newer and better things. It doesn’t mean you should talk to everyone in your life, but you’re going to get a lot of information and sometimes it’s discordant.
Wikipedia and Twitter are not great places to start. That being said, Twitter is a great place to find your tribe, find your network, and link with people. I highly encourage people to reach out on Twitter. I’ve been humbled and awed by the groundswell in patient advocacy.
The PIK3CA Pathbreakers has a huge Facebook group, as do all of the other patient advocacy groups.
Find your tribe. Get anecdotes and stories from all of those people, but be judicious about what information you take in about your own cancer. Don’t necessarily extrapolate everything you hear to your own.
Conclusion
Abigail: The most important thing that patients who are living with breast cancer and their loved ones need to know is that there’s no one right way to do it. What makes you comfortable, what makes you able to handle it, and what makes you able to put cancer into your life, not your life into cancer — that is the right way to live with cancer.
Thank you to Pfizer for supporting our independent patient education content. The Patient Story retains full editorial control.
Kyle’s Journey as a Care Partner Through Love and Loss
Jenny Appleford was a beloved YouTube creator who bravely shared her stage 4 lung cancer journey with the world – not just to raise awareness, but to help others feel less alone. Diagnosed at just 33 with no history of smoking, she used her platform to document everything from treatment updates to quiet family moments, offering a powerful glimpse into life with terminal illness. Her honesty, faith, and fierce love for her family inspired thousands.
In 2023, Jenny passed away – but her voice lives on, not only through her videos, but through her husband, Kyle. In this deeply personal interview, Kyle opens up about what it was like to care for Jenny through her illness, the heartbreak of losing her, and the challenges of navigating parenthood and grief without her by his side. He shares how he’s finding strength, honoring Jenny’s legacy, and learning to live again – one moment at a time.
Jenny was diagnosed with non-small cell lung cancer at 33, despite having no history of smoking. Initially, she was diagnosed with stage 3A but even after different treatments that gave her a good quality of life, they found metastases in her brain. She was later diagnosed with stage 4 lung cancer.
Losing Jenny was an experience filled with unimaginable heartbreak, quiet strength, and enduring love. As her husband and care partner, Kyle tried to remain strong for her and their two young kids, even when inside he was falling apart. In her final days, although confused at times due to the brain metastases, Jenny never stopped being Jenny — full of love, faith, and resilience. She was positive until the very end, always reminding them that she never gave up and that she loved her family deeply.
After Jenny passed, the grief was overwhelming. Kyle had to find a way to balance his pain while supporting their children through theirs. The house was quieter, lonelier, and full of memories, but the responsibilities of being a single parent didn’t stop. He leaned heavily on family and friends, and slowly, found moments of healing.
Grief isn’t linear. Some days, Kyle felt numb; other days, he felt too happy and guilty for it. Therapy, community support, faith, and exercise helped him start to move from just surviving to living again. He misses everything about Jenny — her voice, her parenting, her presence — but he’s learned that it’s okay to grieve at your own pace.
Parenting without Jenny is the hardest. Kyle can’t lean over and laugh with her about what the kids just said or ask her advice in the moment. But he still talks to her, and sometimes, he feels like she answers. Kyle tries to be the best parent he can be, not to replace her but to honor her.
Jenny’s legacy lives on in the way Kyle parents, in the milestones he celebrates with their kids, and in the love she left behind. She was selfless, even in her final days — writing letters for future birthdays and life moments for their kids. Her strength, kindness, and fight to the end left an imprint on everyone she met. She wanted people to enjoy the moment, to fight for more lung cancer research, and to share their stories to help others feel less alone. And that’s exactly what Kyle and their kids are doing.
Watch Kyle’s full interview to hear the raw, emotional story behind these moments:
Hear how Jenny’s final act of love included writing letters for her children’s future birthdays, weddings, and milestones.
Learn what it was like to sit bedside in the final days, holding on to every breath and every second together.
Discover why grief isn’t a straight path and why feeling “too happy” or “too sad” is part of healing.
See how parenting without Jenny has been both heartbreaking and beautiful, with conversations that still include her voice.
Find out how Jenny’s legacy continues through advocacy, everyday moments, and the promise to never let her be forgotten.
Name:
Jenny Appleford
Age at Diagnosis:
33
Diagnosis:
Non-Small Cell Lung Cancer (NSCLC)
Staging:
Stage 4
Symptoms:
Rib pain
Shortness of breath
Treatments:
Chemotherapy
Radiation therapy
This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider to make informed treatment decisions.
The views and opinions expressed in this interview do not necessarily reflect those of The Patient Story.
