For many women, surviving breast cancer feels like reaching the finish line, but sometimes can be the start of a new set of health challenges. One major concern? A higher cardiovascular disease (CDV) risk.
Breast cancer is the second most common cancer among women in the United States. Approximately 80% of breast cancer cases are hormone receptor positive, meaning the cancer cells have receptors for estrogen and/or progesterone -hormones that can stimulate cancer growth. When these hormones bind to the receptors, they can cause the cancer cells to proliferate. Treatments for hormone receptor positive breast cancer include hormone therapies such as aromatase inhibitors (AIs) and tamoxifen. While AIs block the enzyme required to make estrogen, tamoxifen blocks the estrogen receptor, preventing cells from proliferating. This raises important questions: Why are breast cancer survivors at higher risk of CVD? Could cancer treatments, particularly hormone therapy, play a role?
To investigate these questions, Dr. Heather Greenlee, a professor in the Cancer Prevention Program and Public Health Sciences Division, and her team conducted a prospective cohort study examining the association between endocrine therapy use, risk of CVD, and mortality in postmenopausal women with early-stage hormone receptor positive breast cancer. Their findings were published in the Journal of the National Cancer Institute.
The study used data from the Pathways Heart Study, a long-term research effort at Kaiser Permanente Northern California designed to explore cardiovascular and related health risks in women with breast cancer. Researchers identified postmenopausal women diagnosed with early- to mid-stage (Stage I–III) hormone receptor positive breast cancer between 2005 and 2013. Participants were grouped based on their hormone therapy use as non-users, AI-only users, and tamoxifen-only users.
Additional data collected from electronic health records included information on age, race, body mass index (BMI), smoking status, and existing medical conditions like diabetes, high cholesterol, high blood pressure, and prior heart disease.
Over a 7.5-year follow-up period, the team found that women who started AIs within a year of diagnosis had a lower risk of developing major heart issues, including heart failure, compared to non-users. However, the risk of heart attacks and strokes was similar between the groups. Tamoxifen users had no difference in heart risk compared to non-users. Importantly, both AI and tamoxifen users had a lower risk of death from any cause and from non-CVD causes compared to non-users. Notably, women who used AIs had about a 30% lower risk of dying from CVD-related causes.
The team also explored whether body weight influenced the relationship between hormone therapy and outcomes. They found that tamoxifen reduced the risk of all-cause and non-CVD mortality, but only in women with normal BMI. In overweight or obese women, this benefit was not observed. For AI users, body weight did not impact the treatment’s effect on CVD or mortality. A history of CVD before breast cancer diagnosis also did not affect the association between hormone therapy and outcomes.
To ensure the robustness of these findings, the researchers conducted several sensitivity analyses. When comparing tamoxifen users to non-users, non-users had a higher risk of all-cause and non-CVD mortality. No significant differences were found between AI and tamoxifen users in terms of heart disease or death outcomes. When they excluded 242 women with unclear therapy status, the link between AI use and lower heart risk became less statistically strong, but the overall conclusions remained unchanged.
Despite its strengths, the study has limitations. Medication use was inferred from pharmacy records, which doesn’t guarantee that patients actually took their prescriptions. The study also didn’t account for therapy duration or distinguish between different AI drugs. Lastly, treatment patterns may have evolved since the cohort’s 2005–2013 diagnosis period.
Overall, the findings support that hormone therapy -particularly Ais- can help women with early-stage hormone receptor-positive breast cancer live longer without increasing their risk of cardiovascular disease. Although the underlying mechanism remains unclear, future studies should explore this further.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Megan Othus, Richard Cheng, and Heather Greenlee contributed to this research.
The spotlighted research was funded by National Institutes of Health.
Huang Y, Kwan ML, Heckbert SR, Smith NL, Othus M, Laurent CA, Roh JM, Rillamas-Sun E, Lee VS, Kolevska T, Cheng RK, Irribarren C, Nguyen-Huynh M, Hershman DL, Kushi LH, Greenlee H. Endocrine therapy and risk of cardiovascular disease and mortality in postmenopausal breast cancer survivors. J Natl Cancer Inst. 2025
Joss Landazuri is a PhD candidate at the University of Washington in the Microbiology program working at the intersection of biomedical science, public policy, and science diplomacy. As a Latina scientist, communicator, and policy advocate, she is passionate about leveraging her academic training, personal background, and cultural heritage to engage underserved communities in both science and the policymaking process.
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