Chemotherapy vs. endocrine therapy: Why do some women see worse health decline in the years after breast cancer?

Women with a history of breast cancer experience greater physical health decline compared with age-matched women without cancer. But whether this health decline differs in patients who received chemotherapy compared to endocrine therapy is not well understood. In a study published in the Journal of the American Medical Association (JAMA) Network Open, researchers found that physical health decline only occurred in breast cancer survivors who received chemotherapy. “We observed that two years post-diagnosis, the physical health of breast cancer survivors who received endocrine therapy was similar to the physical health of women without cancer of the same age. However, the physical health of survivors who received chemotherapy was lower than the physical health in cancer-free women even five years after diagnosis,” said lead study author Clara Bodelon, a senior principal scientist with the American Cancer Society.The researchers analyzed data from the Cancer Prevention Study 3, which is a prospective cohort of participants in 35 states in the U.S., the District of Columbia, and Puerto Rico between 2006 and 2013. They assessed physical health using the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Scale instrument. The study included 2,566 women diagnosed with breat cander and 12,826 age-matched, cancer-free women. The median age at diagnosis was 56.3 years.Among the women with breast cancer, 1,223 (47.7%) received endocrine therapy, 276 (10.8%) received chemotherapy, and 634 (24.7%) received both. Compared to cancer-free women, there was a greater physical health decline within 2 years of diagnosis for breast cancer survivors receiving endocrine therapy, chemotherapy or both. The decline among endocrine therapy users was restricted to women receiving aromatase inhibitors. “The biological mechanisms underlying chemotherapy and endocrine therapy are very different, and so I expected that the health consequences would be different. But nobody had reported this,” said Bodelon in an email to the Medical Post.The statistical analyses were conducted between May 2023 and December 2024. Since breast cancer is a heterogeneous disease, current treatment guidelines are based on tumour characteristics and include a variety of combinations involving surgery, radiation, chemotherapy and endocrine therapy. The study population included 184 Asian (1.2%), 418 Black (2.7%), 731 Hispanic (all races) (4.8%), and 13,758 white (89.4%). A better understanding of the survivorship care needs “As treatment recommendations change over time, we need to better understand the long-term health consequences of those treatments. This can inform physicians and healthcare providers for cancer survivors of the long-term needs they may have,” Bodelon said. “It is important to develop a long-term care plan for cancer survivors, and what goes into that plan is likely dependent on the treatment they received.”The authors note there are significant limitations with this type of study. Treatment information was limited to frontline treatment, and they did not have information on the types of chemotherapy received. Further, there was no information on other treatments, such as targeted therapies or immunotherapies. Dr. Bernard Tawfik, who is an associate professor and chair of the Commission on Cancer at the University of New Mexico Comprehensive Cancer Center, said breat cancer survivorship continues to become a larger issue each year because treatments are improving and so is longevity. “Our therapies are becoming more advanced and curing more patients more often. To address this change, we need to understand the needs of cancer survivors, support in their survivorship journey and tailor therapies to minimize long-term toxicities,” said Dr. Tawfik.In this cohort, women diagnosed with breast cancer were more likely to have a BMI of 30 or greater (750 women [29.2%]) compared with women without cancer (3,376 women [26.3%]). However, other characteristics were similar between groups. Most women were diagnosed after 2015 (1,375 women [53.6%]) with tumours that were hormone receptor positive (2,109 women [82.2%]), localized (1,405 women [54.8%]) or in situ (608 women [23.7%]). Dr. Arash Asher, director of Cancer Rehabilitation and Survivorship at Cedars-Sinai Cancer in Los Angeles, said accelerated aging through DNA damage, telomere shortening, oxidative stress and inflammatory pathways drives many of the unmet needs of breast cancer survivors. “This includes challenges such as cancer-related cognitive impairment (‘chemobrain’), cancer-related fatigue, bone loss, chemotherapy-related neuropathy and deconditioning, among others,” said Dr. Asher. “We need to learn how to tailor dietary interventions to the microbiome and metabolic needs of each individual patient.”The cohort included 433 women with breast cancer (16.9%) who did not receive chemotherapy or endocrine therapy, and 1,223 women with breast cancer (47.7%) who received endocrine therapy without chemotherapy. The study also included 276 women with breast cancer (10.8%) who received chemotherapy without endocrine therapy, and 634 women with breast cancer (24.7%) who received chemotherapy and endocrine therapy. Among the 1,857 women (72.4%) who received endocrine therapy, 591 (31.8%) used tamoxifen, and 888 (47.8%) used aromatase inhibitors. Physical health was assessed at four different times and 1,455 women without cancer (59.4%) and 126 women with breast cancer who received endocrine therapy without chemotherapy (59.4%) reported having excellent or very good health five years after diagnosis. However, only 23 women who received chemotherapy without endocrine therapy (41.8%) and 66 women who received chemotherapy with endocrine therapy (50.0%) reported having excellent or very good health.Dr. Norah Lynn Henry, who is a medical oncologist at the University of Michigan, said early detection of breast with mammograms, combined with more effective therapies for treatment of the disease, have led to an explosion in the number of women and men who are living with a history of breast cancer. Dr. Henry said it is important to provide resources to enable patients to adopt healthy lifestyle choices, including those related to exercise, diet, alcohol and stress, which is likely to improve the overall quality of life for survivors of breast cancer. “For example, exercise has been shown to improve physical function and to reduce fatigue in patients with cancer, although often patients who don’t routinely exercise aren’t sure where to start,” said Dr. Henry.Reference:Clara Bodelon, Matthew Masters, Den E Bloodworth, et al. Physical Health Decline After Chemotherapy or Endocrine Therapy in Breast Cancer Survivors JAMA Netw Open. 2025;8(2):e2462365. doi:10.1001/jamanetworkopen.2024.62365

Chemotherapy vs. endocrine therapy: Why do some women see worse health decline in the years after breast cancer?

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