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Dr. Kevin Kalinsky discusses the role of targeted therapy and clinical decision-making in managing estrogen-driven, HER2-negative breast cancer.

Dr. Kevin Kalinsky Covers Targeted Therapy in HER2– Breast Cancer

I am currently starting treatment with a BTKi, or Bruton’s tyrosine kinase Inhibitor, which represents an important advancement in targeted cancer therapies. These drugs were approved about 10 years ago following extensive clinical trials and have since become a cornerstone in the treatment of chronic lymphocytic leukemia (CLL). BTKis work by blocking a key enzyme, Bruton's tyrosine kinase, which is essential for the signaling pathway that drives the survival and proliferation of malignant B cells. By inhibiting this enzyme, therapy helps control the growth of CLL cells, slowing disease progression.

CLL is a type of cancer that originates in the bone marrow, affecting a specific type of white blood cell called lymphocytes. These cells are crucial for the immune system, helping the body fight infections. In CLL, however, they grow uncontrollably, crowding out healthy blood cells and impairing the body’s ability to fight infections. Despite being a form of leukemia, CLL is characterized by the slow and often indolent progression of these malignant lymphocytes.

As with any medication, BTKis come with their own set of side effects. I have new bruising and moderate night sweats and watch for any new infections. Additionally, in some cases, these drugs may inadvertently trigger autoimmune responses or worsen pre-existing autoimmune conditions, making the management of side effects a delicate balance. Each patient's experience with treatment is unique, requiring ongoing monitoring and adjustments. I have a blood test every week for the next six weeks.

We have a single daffodil outside our front door that blooms each spring. It serves as a poignant reminder of the delicate balance in nature — and, by extension, in life. The daffodil is a hardy flower, but like me, it is vulnerable to extremes. It wilts when the temperature shifts too drastically. Too cold, and it succumbs to the chill; too hot, and it withers in the heat. Much like the fragility of health, the daffodil requires care and understanding to thrive. It reminds me that resilience is not about avoiding change or hardship but about adapting to what is thrown our way.

As spring unfolds in Santa Fe, New Mexico, the weather in the foothills of the Sangre de Cristo Mountains mirrors this dance of resilience. The mountains, named for their reddish hue when covered in snow, stand as a symbol of enduring strength. The Spanish explorer who named them, impressed by their vibrant colors, called them "the blood of Christ" in 1719 — a name that endures as a reminder of nature’s permanence.

Surrounding Santa Fe are the Pueblo communities of Nambe, Pojoaque, San Ildefonso, Ohkay Owingeh, Santa Clara and Tesuque. These communities have a deep spiritual and cultural connection to the land. They have many names for the mountains in their native Tewa language — names rich with history and meaning but not easily translatable into English. Their connection to the land is woven through the centuries, shaping their way of life even as they face new challenges brought by drought.

The landscape here in Santa Fe is stark and beautiful, reflecting both the allure and the challenges of living in a high desert environment. The discomfort of extreme dryness and strong winds is forgotten when viewing the mountains, the blue sky and the dramatic sunrises and sunsets. Many artists have come here to paint, drawn by the brilliance of the colors and the clarity of the light.

The juniper trees are blooming this time of year, and clouds of pollen hang in the air, carried by the wind. It’s an annual reminder that the climate here is shifting in subtle yet powerful ways. Everyone in the community feels it, sneezing and rubbing their itchy eyes. Like many of my older neighbors and friends, I have developed dry eye syndrome, where the body does not produce enough tears. Fortunately, I found an effective eye drop medication that relieves my symptoms.

This year, we are amid a severe drought, with very little snow and no substantial rainfall during the winter months. As a result, fire season is arriving earlier than usual, and the threat of wildfire looms large. Like cancer, we must be on guard, prepared for change, and ready to find safer ground if necessary. That preparation is important, but we must not let it consume us with anxiety or worry.

These incremental changes in the climate create a challenging environment for gardening. Yet, much like the Pueblo people, we have found ways to adapt. The acequia system, a traditional network of community irrigation ditches, has been a key part of Pueblo agriculture for centuries. These ditches are not just physical canals; they represent a community effort to manage water resources collaboratively. The acequia system embodies self-governance and shared responsibility, teaching us that resilience is not only an individual effort but a collective one.

Adapting and Finding Strength in Uncertainty

Our gardening practices reflect similar strategies for resilience. By planting fruit trees closer to the house and growing vegetables in containers, we protect them from the unpredictable spring winds and cold nights. This approach mirrors my own journey with cancer. Just as gardening requires careful planning, adaptation, and resilience in the face of changing seasons, managing cancer demands flexibility and a strategic mindset.

It isn’t easy having cancer. But like gardening in a harsh climate, survival and growth come from strategies, adaptation, and patience. Every change — whether in the weather or the course of treatment — requires a thoughtful response. In this way, both gardening and health teach us the value of resilience: the ability to adapt, to adjust, and to continue growing, no matter the circumstances.

By aligning myself with the resilience observed in nature and the wisdom of the communities around me, I feel empowered to face the challenges of my treatment. Just as the daffodil, the Pueblo people and the acequias have adapted to their environment, we too, will adapt and thrive through this journey. It is our community, and we can do better working together.

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subscribe to CURE®’s newsletters here.

Bruton’s tyrosine kinase inhibitors (BTKis) have revolutionized chronic lymphocytic leukemia (CLL) treatment by targeting a crucial enzyme in malignant B cell survival. While effective, these therapies come with side effects, necessitating careful management and monitoring. The narrative draws parallels between personal health challenges and the resilience required in nature and community life, particularly in the context of Santa Fe's climate and cultural heritage. The acequia system exemplifies collective resilience, emphasizing the importance of adaptation and community support in overcoming adversity, whether in health or environmental challenges.

It isn’t easy having cancer. But like gardening in a harsh climate, survival and growth come from strategies, adaptation, and patience.

Tumor

Managing Cancer Demands With Flexibility and a Strategic Mindset

In today’s world, I sense a real despondency I have never seen before. Horrible divisions have split our country and the world, including family and friends. Countries are at odds with each other, and people are losing their jobs and benefits. Prices are soaring, and people are struggling to pay their bills.

Some of my friends and relatives are so distressed they cannot bear to watch the news. A few are experiencing nightmares, while others watch the news for hours and post everything on social media. It is easy to forget the good happenings like neighbors, friends, volunteers and agencies serving others hot meals, helping through storms and providing shelter.

I admit I am just as angry and worried as everyone else, and the rhetoric is personal for me. I worry that the research presently being done on cancer and other diseases may be stopped. The only reason I am still alive is because of the ongoing research.

I am dismayed at people with disabilities being deprived of services because I have worked with this population my entire life. I was a children’s librarian, and I know how important education is to our society.

I then think back to the origins of COVID-19 and how scared we all were. We felt alone and frightened, not knowing what the future would bring and if a vaccine would be perfected. Some of us were not able to visit family far away or see our loved ones in nursing homes.

However, we were kind to each other. We cheered and supported our medical personnel and our teachers. We helped as much as we could and watched over our neighbors.

Most of that went away after the pandemic was over. Why? Because the pandemic distracted us from our daily duties and we focused on the most important things in our lives, which were families and friends. 

Let me fast forward to the present as I try once again not to panic, although some of these fears are justified. It has occurred to me that the reason I am not as devastated as some is I am a cancer survivor.

I witness the doctors, the nurses, the people who are keeping me alive and do care. I am distracted because I am fortunate to see the good that many people can do in the middle of this horrible disease. I have had to make life-changing decisions, such as having a bone marrow transplant. Being alive is a miracle in itself.

Amazingly, a terrible diagnosis like cancer has given me and others a different perspective than most. We know the world is in an awful place right now. However, we have survived this far, and life will continue.

Cancer is a distraction and not always a bad one. We do learn perspective. There are some good things we can take away in tragic events, whether it is a pandemic or experiencing cancer.

These tragedies force us to ignore other distractions and focus on the crucial events in our lives, which include our relationship with families, our battles with cancer and the medical personnel who help us. These negatives can become positive.

We have had rough lessons with this formidable disease, just like with COVID-19, but sometimes, it prepares us for life’s more significant lessons, and that is good.

The current global climate is marked by division, economic struggles, and widespread despondency, affecting individuals' mental health and daily lives. Despite these challenges, the author finds solace in the resilience and kindness witnessed during the COVID-19 pandemic and through personal experiences as a cancer survivor. These adversities have provided a unique perspective, emphasizing the importance of focusing on meaningful relationships and the positive impact of medical professionals. Tragedies like pandemics and cancer can offer valuable life lessons, transforming negatives into positives and fostering personal growth.

In an upside-down, topsy-turvy world, cancer can be a distraction for us.

Sometimes Cancer is a (Welcome) Distraction

I never knew how incredibly difficult it is to be a single parent, especially without family nearby to help. That is until my husband of 25 years, Dan, passed from cholangiocarcinoma and I had to take care of our son, Alex, who is autistic. Without the safety net of another caretaker nearby and my chronic health problems, it became painfully obvious that I needed help. I could not keep up with Alex’s increasingly fast stride, calm him during outbursts of frustration or help him with all of his daily living skills.

Two years after Dan’s death, I found a group living situation for our son. Even though I check on him regularly, it is still hard parenting alone. I feel guilty because I know if Dan had lived, Alex would be at home with us.

With this secured, I finally was able to have knee surgery that I had put off for many years.
As a spouse of someone with cancer, I had experience on how to plan and schedule. This included how long to take off work, rides for physical therapy appointments and which friends I could count on to help with everything from food preparation to laundry and picking up prescriptions.

Unfortunately, I was four weeks out from surgery when I pulled up from my desk and the left knee buckled. It took two paramedics to help me back into a chair. I planned for the first surgery, but not for the second.

Two days later, I woke up with a wound bag, an immobilized knee and a three-week hospital stay which included rehab. The second surgery ignited a traumatic response in me because it was reminiscent of the times treatments and surgeries failed for my husband. This robotic limb had screwed me over. Mostly, I was terrified that after a month of helping me, I would run out of friends who had sacrificed their time to get me through what was supposed to be a shorter recovery. Who would check on my son? Who would drive me around to appointments? Now I was in a heavy immobilizer brace for at least two more months. I could barely walk, and could not drive for several months, at least.

Solo parents not only face daily challenges, but catastrophic ones as well. I did not have an adult child that I could count on, nor family willing to take time off from work to help. Because I had spent most of my parenting years with a partner, I had never understood the total despondency of being in crisis and alone.

In rehab, I met Yeshi, who was one of the nurse’s aides and a single mom from Ghana, who raised three children on her own. As miserable as I was, I could not imagine taking care of my son alone in a foreign country, learning another language and putting myself through school. I also bonded with another aide whose pre-teen son had autism and was struggling in the school system. She felt she had no choice but to bring him back to Cameroon where the education system might better meet his needs and extended family could help.

These conversations fueled my desire to heal. They made me appreciate the hardships single parents face every day. I truly did not get it until I had time to process my own situation by reflecting on theirs.

Since I’ve been back home, my friends have re-emerged for yet another round. Staff have brought my son to see me. The hospital discharge staff provided me with resources and community groups have pitched in. One good thing that has come out of this experience is that I have expanded my network. I learned that single parents network as a means for survival.

A few of my succulents died while I was away, so I sneaked in some artificial plants with colorful blooms. Some people can’t tell the difference because they are so carefully woven into the soil. They get tangled among the real stems and leaves and become almost inseparable. The perfectionist in me knows that this is cheating. I want to yank those imposters out forgetting that they were purposefully placed there to make it seem like I have a green thumb.

This is how I view parenting. You do the best you can and fake the rest so the outside world thinks you have it under control, but really you are just living day to day hoping not to mess things up too much. I can’t say that I have the life I always wanted or that my life is significantly better or worse. Maybe it’s not wise of me to think of life in that way. Cautiously, I roll my walker to the armchair, understanding and admiring the survivor parents whose resilience prompts them to get up every morning and do it all again.

Losing a spouse to cancer and becoming a single parent to an autistic child presents immense challenges, especially without nearby family support. The author shares their journey of navigating these difficulties, including undergoing knee surgery and facing unexpected setbacks. Through interactions with other single parents, they gain a deeper appreciation for the resilience required in such circumstances. The experience highlights the importance of community support and networking for survival. Ultimately, the author reflects on the imperfect nature of parenting and the daily perseverance it demands.

Despite the initial shock and challenges, I found strength and support within the community of single parents.

When A Spouse Dies from Cholangiocarcinoma: Praise for Single Parents

Among patients with previously untreated chronic lymphocytic leukemia (CLL), Calquence (acalabrutinib) plus Venclexta (venetoclax) with or without Gazyva (obinutuzumab) significantly prolonged progression-free survival when compared with chemoimmunotherapy, according to study findings published in 

After a median follow-up of 40.8 months, the estimated 36-month progression-free survival was 76.5% with Calquence and Venclexta, 83.1% with Calquence plus Venclexta and Gazyva, and 66.5% with chemoimmunotherapy. Estimated 36-month overall survival was 94.1% with Calquence plus Venclexta, 87.7% with the Calquence combination and 85.9% with chemoimmunotherapy.

“Results for progression-free survival suggest that the benefit of adding [Gazyva to Calquence and Venclexta] was most apparent in the subgroup with unmutated IGHV, which had results that were similar to those in the subgroup with mutated IGHV,” Dr. Jennifer R. Brown and colleagues wrote in the study. “In addition, overall survival was significantly prolonged with [Calquence plus Venclexta] as compared with chemoimmunotherapy.”

Brown is the director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School in Boston.

Side effects leading to discontinuation of Calquence occurred in 7.6% and 13.7% of patients in the Calquence plus Venclexta, and Calquence plus Venclexta and Gazyva groups, respectively. Dose reduction occurred in 14.1%, 20.8% and 11.2% in the three groups. Infections and neutropenia were the most common reasons for treatment interruption and dose reduction.

Serious side effects were reported in 24.7%, 38.4% and 27.4% of patients in the three groups. Cardiac events and second primary cancers were more common in the Calquence plus Venclexta (9.3% and 5.2%) and Calquence plus Venclexta and Gazyva (12% and 4.2%) groups compared to the chemoimmunotherapy group (3.5% and 0.8%). Basal cell and squamous cell carcinomas occurred more often in the Calquence plus Venclexta group.

Hypertension occurred in 4.1%, 3.9% and 2.7%, and grade 3 (severe) or higher neutropenia was reported in 32.3%, 46.1% and 43.2%. Tumor lysis syndrome was observed in 0.3%, 0.4% and 3.1% of patients.

Deaths from any cause were reported in 18, 37 and 42 patients in the three groups, with COVID-19-related deaths occurring in 10, 25 and 21 patients, respectively. Of the 56 COVID-19-related deaths, 48 occurred in 2020 and 2021.

“The safety profile of fixed-duration [Calquence plus Venclexta] in this trial aligned with that in previous studies of [Calquence],” study authors wrote.

A total of 867 patients were randomized with 291 assigned to Calquence plus Venclexta, 286 to Calquence plus Venclexta and Gazyva and 290 to chemoimmunotherapy. Of those in the chemoimmunotherapy group, 143 received fludarabine and cyclophosphamide and rituximab and 147 received bendamustine-rituximab. The median patient age was 61 years, and 58.6% had unmutated IGHV.

This phase 3 open-label trial enrolled patients 18 or older with an Eastern Cooperative Oncology Group performance-status score of 0 to 2 and no 17p deletion or TP53 mutation. Participants were randomly assigned to receive either Calquence plus Venclexta (Calquence in cycles 1 to 14; Venclexta in cycles 3 to 14), Calquence plus Venclexta and Gazyva (same regimen with Gazyva in cycles 2 to 7) or chemoimmunotherapy with fludarabine and cyclophosphamide and rituximab or bendamustine and rituximab (cycles 1 to 6), as chosen by investigators.

“Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia,” by Dr. J. R. Brown, et al

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In a study of untreated chronic lymphocytic leukemia (CLL) patients, Calquence (acalabrutinib) combined with Venclexta (venetoclax), with or without Gazyva (obinutuzumab), significantly improved progression-free survival compared to chemoimmunotherapy. The 36-month progression-free survival rates were 76.5% for Calquence and Venclexta, 83.1% with Gazyva, and 66.5% for chemoimmunotherapy. Overall survival was also higher in the Calquence groups. Side effects included infections, neutropenia, cardiac events, and secondary cancers. The study involved 867 patients, with a median age of 61, and highlighted the safety profile of the treatment.

Calquence plus Venclexta with or without Gazyva significantly improved progression-free survival in patients with untreated CLL. 

Calquence Combo May Improve Outcomes in Chronic Lymphocytic Leukemia

As a cancer veteran, I'm witnessing some beautiful things going on in the lives of people I know with cancer. And I'm learning that life does go on despite an often-wicked diagnosis.

For instance, Jean, a friend of mine, has stage 4 thyroid cancer, but thank God the cancer isn't getting any worse. At least that's what her frequent scans say. Even though she has this cancer diagnosis hanging over her head, she doesn't let it keep her from living her life. In fact, she is the family "ringleader," as her cousin describes her. She gives many of the parties and tries to keep their family together. A job that once belonged to the family's paternal grandmother, Jean is the hostess who throws frequent get-togethers for family and friends. When I'm in New York, I often attend a gathering at her home. Jean is one of the most cordial and welcoming people I know.

My brother, who was recently diagnosed with stage 1 Waldenstrom, a type of non-Hodgkin's lymphoma, is the chief caregiver of our 93 year-old mother, who has Parkinson’s disease. He helps her with her daily care such as bathing, dressing, and preparing meals. It's Mike who puts my mother to bed at night. Mike and my mom live a quiet life; they are known to take long drives during the day and watch Lawrence Welk nightly. His primary role is to keep her from falling. About a year ago, Mom fell, due to Parkinson’s, and broke her hip. Mike tries hard to prevent this from ever happening again, but sometimes a fall comes out of nowhere. The other day, it was so windy outside that a gust of wind knocked Mom over. Luckily, she wasn’t hurt in the fall.

Another friend of mine, Maggie, has breast cancer, stage 1. Years ago, Maggie and her husband, Robert, divorced, but Robert is currently helping Maggie through her cancer. In fact, Maggie’s cancer is, in a way, bringing the ex-couple closer. Robert is accompanying her to radiation treatments. A couple once alienated from each other, now can work together to keep Maggie alive.

Another couple I know share something in common: they both have cancer. The husband has prostate cancer, and the wife has breast cancer. They take care of each other, watching what they eat and exercising together as much as they can. This couple doesn’t let the disease slow them down, but the hardship seems to make them love each other even more.

In short, for some, cancer brings out resiliency and fellow feeling; for some, cancer may make some folks unsinkable and incredibly psychologically strong.

Ironically, for me, cancer did the opposite. I was laid low by my stage 2 breast cancer. The thought of throwing a party during that time was unthinkable. As far as caring for people, I could hardly care for my young son. This might have been because I was also dealing with bipolar disorder. I was both physically and mentally impaired. Thank God my husband was there to do the hard work of keeping the family together as I endured a double mastectomy, chemotherapy, and radiation therapy.

However you are going through cancer, whether you're thriving with the disease or just barely making it, I wish you the best. God knows it's hard either way. I hope your life goes on.

Cancer can evoke resilience and empathy, as seen in individuals who continue to live fulfilling lives despite their diagnoses. Examples include a woman with stage 4 thyroid cancer who remains a family leader, a man with stage 1 Waldenstrom's lymphoma caring for his elderly mother, and a divorced couple reconnecting through breast cancer treatment. Another couple supports each other through their respective cancer battles. While some find strength and connection, others, like the author, may struggle due to additional challenges such as mental health issues.

I reflect on how cancer has brought out resilience and support in others, even as I struggled with my own battle, and wish others strength in their journeys.

Life Goes On, Even With Breast Cancer

I was diagnosed with diabetes at the age of 60. Ten years later, I was diagnosed with chronic lymphocytic leukemia. When my primary care physician diagnosed me as diabetic, it wasn’t a shock because my father was diagnosed at the age of 20, while in the Army. I always knew I had a 50/50 chance of becoming diabetic because this was part of my family history. With that in mind, I worked hard to exercise, eat right, and watch my weight. And I always followed up with yearly checkups.

However, when the reality hit me, I became angry and depressed. I couldn’t understand how this could happen to me since I’d done all the right things, especially keeping my weight under control. I’m a medium-frame guy, 5 feet, 8 inches tall, and for my entire adult life, I’ve weighed between 140 lbs. and 150 lbs. But then I realized that genetics plays a big role in my makeup, so I was predisposed to diabetes from the very beginning. There was one thing that helped me to deal with my depression. My primary care physician called me in for a consultation and said the following:

“Chester, just think, you’ve been free of diabetes for 60 years. So, let’s focus on all those years and how grateful you can be for that. Since your father was diabetic, the family genetics were not on your side.” At that moment, his words hit me, and my spirits were lifted. He said, “I’ve been your doctor for 20 years, and I know you can cope with this. You have the strength. I know this about you.” It’s amazing how the words of a doctor can inspire us and encourage us to do the right thing.

The next time I went for a checkup, my A1C was perfect, and my PCP was proud of me. His support meant everything to me.

Then over the past few years, cancer came into my life and uprooted my balance. I felt as if I was walking a tightrope and tilting over all the time to hold myself together.

In doing some research, I discovered that diabetes itself can make us vulnerable to other diseases. Then I discovered that my medication, metformin, could make me susceptible to other cancers such as prostate, colorectal, and even breast cancer. There is controversial research about this drug, but I’m still taking it and hoping it helps. I’m also taking Jardiance, which reduces the risk of cardiovascular and kidney disease. But it too has a harmful side effect of causing ketoacidosis. Fortunately, I haven’t experienced that side effect. Either way, it means that I’m in a precarious position. It's like a double whammy!

When I began chemotherapy for my chronic lymphocytic leukemia, I learned more lessons, which were outlined in my essay, “What I’ve Learned about Having Cancer.” My oncologist prescribed medication for nausea and vomiting before the chemotherapy started. Fortunately, that worked, and I didn’t experience any of those symptoms. However, the very medication that was used to treat my cancer was also raising my blood glucose level.

Eventually, my oncologist and primary care physician worked together and prescribed Ozempic. This medication resulted in weight loss to the extent that the doctors discontinued that medication. I was never overweight, and this weight loss began to make me look like a skeleton.

Managing dual diagnoses of diabetes and chronic lymphocytic leukemia presents significant challenges, requiring lifestyle adjustments and medical interventions. Despite a family history of diabetes, proactive health measures were initially effective. However, the onset of cancer and its treatment complicated diabetes management, necessitating medication adjustments and dietary changes. Stress, exacerbated by personal and financial issues, further impacted health. Emphasizing mindfulness, spiritual reflection, and a supportive healthcare team, the journey involves continuous adaptation and resilience. The focus remains on balancing medical treatments, diet, and mental well-being to navigate this complex health landscape.

Managing diabetes and chronic lymphocytic leukemia is challenging, but with proactive care, mindfulness and diet changes, I'm working to balance both.

Dr. Kevin Kalinsky

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