Posted on January 11, 2024

By Zoë Christopher, MA, BCAction Program Officer

Treating Triple-Negative Breast Cancer and Early Stage HER2+ Breast Cancer in Older Adults

My time at Breast Cancer Action now extends into its 17th year, with only a few years less as the Resource Liaison. I receive an increasing amount of correspondence from people 65 years and older who are dealing with a breast cancer diagnosis, and I also hear from their friends, family members, and caregivers. Their concerns, particularly regarding treatment, are often unique to an older population.

Ana Sandoval-Leon, MD, a breast cancer oncologist with the Miami Cancer Institute, presented on Systemic therapy in geriatric patients with triple-negative breast cancer. Breast cancer (BC) incidence increases with age, and she noted that it’s the leading cause of new cancer diagnoses in women in the United States. Although the median age of diagnosis is 63 years, over a third of patients diagnosed, and about half of the BC mortality in Western societies, are people over 70 years of age. 

Overall, outcomes for early-stage BC have improved. Despite the lower incidence (12%-15%) of triple-negative BC (TNBC), the five-year survival is 8-16% lower than in hormone receptor-positive BC. With the improved life expectancy in the United States and the increased incidence of BC as patients age, it is of vital importance to know how to treat BC in the elderly. Unfortunately, optimal management of BC among the elderly has not been adequately studied due to underrepresentation in clinical trials. Furthermore, there is limited information on the potential toxicity and real benefits of chemotherapy in older patients.

Dr. Sandoval-Leon presented a retrospective analysis of data collected from the National Cancer Database (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, covering the years 2004 to 2019. Women 65 years and older with early-stage TNBC (stages I-III) were included in the analysis. Patients were categorized into three treatment groups: those who did not receive chemotherapy, those who received chemotherapy, and those who received chemotherapy + immunotherapy. After adjusting for multiple variables, the age cutoff over which the survival rates were not significantly different between two treatment groups (those who received no chemotherapy and those who received chemotherapy + immunotherapy) was identified.

Among patients who were older than 81 years with early-stage TNBC, those who received treatment with chemotherapy + immunotherapy did not have an overall survival benefit as compared to those who received no chemotherapy. Limitations of this study include the small number of patients older than 81 years who received chemotherapy, which could explain why a statistically significant benefit of chemotherapy + immunotherapy could not be identified. Another limitation is that it was not possible to assess breast cancer–specific mortality. However, Dr. Sandoval-Leon’s analysis highlighted the importance of individualizing treatment recommendations in older patients who may not garner the same benefit of treatment as younger patients. It’s clear that additional studies are required to clarify contributing factors and to help optimize the management of geriatric patients with TNBC. 

Dr. Reshma L. Mahtani, DO, chief of breast medical oncology at the Miami Cancer Institute, presented on Chemotherapy in geriatric patients with early-stage HER2+ breast cancer. 

Because life expectancy has increased in the US due to improvements in medical care, the number of older patients with a BC diagnosis is also expected to increase. The population of individuals 80 years and older in the US is growing and now comprises more than 9 million. Approximately 15% of BC is HER2+. The combination of chemotherapy with Herceptin (trastuzumab), with or without PERJETA® (pertuzumab), a targeted therapy, compared with Herceptin alone has been shown to be cost-effective in patients 70 years and older, but Herceptin monotherapy could be considered as an option in certain patients. Nevertheless, there are limited guidelines on how to properly care for the geriatric population with HER2+ breast cancer. 

Dr. Mahtani also presented a retrospective analysis of data collected from the NCDB, the joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. Women 65 years and older with stage I, II, and III HER2+ BC were included in the analysis. Patients were categorized into three treatment groups — those who did not receive chemotherapy or monoclonal antibodies*, those who received chemotherapy in combination with monoclonal antibodies, and those who received monoclonal antibodies alone. Two comparisons were made: 1) no chemotherapy or monoclonal antibodies vs. chemotherapy with monoclonal antibodies, and 2) chemotherapy with monoclonal antibodies vs. monoclonal antibodies alone.

*Note: True chemotherapy agents consist of chemicals that kill fast-growing cancer cells while generally sparing slower-growing normal cells. Antibodies, by contrast, are not chemicals but proteins that target specific molecules on the surface of cancer cells. And monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, modify or mimic the immune system’s attack on cells that aren’t wanted, such as cancer cells. (Mayo Clinic website, 12/14/23) 

For the first comparison, a total of 9,924 HER2+ early-stage BC patients were included. Of these, 3,052 (30.8%) met the first criteria above, while 6,872 (69.2%) received chemotherapy with monoclonal antibodies. Kaplan Meier curves comparing mortality by treatment in the whole sample showed that those in the second group had significantly improved survival compared to the first group. The one-year and three-year survival rates were significantly higher in the second group compared to the first. In the whole sample, all-cause mortality was significantly lower among patients in the second group compared to those in the first.

For the second comparison, a total of 7,457 patients were included. Of these, 6,872 (92.2%) met the second criteria above, while 585 (7.8%) received monoclonal antibodies alone. The one-year and three-year survival rates were significantly higher in the first group compared to the monoclonal antibodies alone.

Chemotherapy in combination with HER2-directed monoclonal antibodies showed a survival benefit in elderly patients, irrespective of age, when compared to no chemotherapy or monoclonal antibodies and monoclonal antibodies alone. Dr. Mahtani pointed out that these data highlight the importance of individualizing treatment recommendations and not forgoing standard therapy based merely on age. Limitations of the analysis include a lack of available information on BC-specific mortality. Also, the benefit that was identified could be secondary to selection bias. Again, as shown in Dr. Sandoval-Leon’s presentation, additional studies are needed to improve the treatment in elderly patients with HER2+ breast cancer. 

Standard treatment for early-stage HER2+ breast cancer is chemotherapy plus a targeted therapy such as Herceptin, which improves overall survival in comparison to a targeted therapy alone. But the effects of toxicity often increase in geriatric patients.

Following these presentations, I have a slightly improved understanding of the complexities of clinical trials involving older patients. I also feel frustrated that none of these comparisons of various treatments also looked at the nuanced roles of comorbidities in the survival data.

When BCAction receives calls or emails from older people, it’s usually when they are trying to make treatment decisions. Their greatest concerns involve quality of life issues vs. long-term survival, and these concerns are deeply personal. Sometimes, longevity is at the top of their priority list; they want to live long enough to become a grandparent or see a family member get married. One woman I spoke with wanted to live long enough to finish her PhD dissertation, and dealing with the side effects of treatment was secondary to her goals. Sometimes, quality of life is the priority; they feel side effects of treatment would impede their ability to live fully, even if modified treatment or opting out of treatment means they won’t live as long. And I’ll never forget the heartbreaking call I received from a loving granddaughter who wanted me to convince her grandmother to accept treatment.

I want to better understand the patient’s perspective on treatment; I want to hear the patient’s voice. But since I didn’t think I was going to get what I wanted, I turned to a study by Flannery, MA, et al. titled Understanding Treatment Tolerability in Older Adults with Cancer, in the Journal of Clinical Oncology, dated May 27, 2021. 

The authors note that “‘The treatment cannot be worse than the disease’ is an oft-cited statement representing the important concept of tolerability; older patients often express concerns about side effects during decision making for cancer treatment. Tolerability, defined by the International Council for Harmonization as ‘the degree to which overt adverse events can be tolerated by the subject,’ has been historically quantified solely using clinician ratings of adverse events (AEs).

This study included the lived experiences of patients or the patient-reported measures of tolerability. The authors highlighted the need for in-depth conversations between patients and their physicians so that physicians can learn what matters to the patient, what the patient is actually experiencing, and how the patient feels about it. This has to be at the foundation of understanding treatment tolerability in older adults. 

Noted in the same study, “To date, research has identified higher toxicity in older patients with cancer and it has established mechanisms for assessing risk. Continuous research efforts are needed, however, to expand understanding of tolerability for specific treatment regimens, to identify persistent long-term tolerability concerns, and to implement management efforts in clinical practice.” Out of this study, the authors developed “…a model that incorporates a multidimensional perspective on the components of tolerability to stimulate research and guide clinical implementation efforts.” They acknowledge the need for an understanding of tolerability beyond clinician-rated assessments.

I cannot help but feel all of us — clinicians, loved ones, family members, caregivers, advocates — need to step back, take a breath, and listen to patients. The Flannery study concluded, “Patient values, goals, and concerns about desired treatment benefits and unacceptable risks are of paramount importance; in pretreatment discussions, it is essential to learn how the patient perceives tolerability and what matters to them, especially in the context of uncertainty about benefits and risks.” I couldn’t agree more, and I hope to see the issue addressed more specifically at the San Antonio Breast Cancer Symposium next year.