Cardiovascular Toxicity Following Aromatase Inhibitor Use
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Non-technical overview of the research topic and relevance to breast cancer:
 
 
 
 Aromatase inhibitors (AIs) are becoming the cornerstone in breast cancer treatment among post-menopausal survivors with hormone-positive disease. AIs reduce recurrence risk, but this risk is modest among women diagnosed with early stage breast cancer. By contrast, a major cause of death in breast cancer survivors is cardiovascular disease (CVD). Although clinical trials evidence suggests that AIs have a greater advantage in reducing recurrence, the long-term effects of AIs on the cardiovascular system are unknown. New evidence suggests that AIs might increase the risk of CVD, but very few studies were able to follow women long enough to determine if CVD risk is truly greater who take this medication. As AIs became generic in 2010, it is possible that tens of thousands breast cancer survivors may inadvertently be at greater risk of CVD in the future. Coupled with this new concern, a recent study suggests that taking tamoxifen for ten years may reduce mortality risk and maybe cardio-protective. Hence, clinical decision-making on the optimal endocrine treatment choice has become complex. Given this background, our study is timely.
 
 
 
 
 
 
 
 The question(s) or central hypotheses of the research: 
 
 
 
 Given the growing number of breast cancer survivors prescribed AIs, determining the long-term cardiovascular side effects is a major clinical concern. Therefore, our aims are to: 1) Examine the risk of new CVD (including stroke) in a large community cohort of nearly 30,000 breast cancer survivors exposed to various adjuvant endocrine treatments (AIs, tamoxifen) followed up to 20 years post diagnosis, and examine the interaction of these medications with other potential cardiotoxic treatments such as certain chemotherapy and radiation treatments. 2) Generate a risk/benefit tool to help clinicians in the treatment selection of AIs versus tamoxifen for postmenopausal patients diagnosed with breast cancer.
 
 
 
 
 
 
 
 The general methodology:
 
 
 
 Our overarching goal is to examine the risk of CVD in a diverse cohort of nearly 30,000 breast cancer survivors by adjuvant endocrine treatment (AIs, tamoxifen, switchers, non-users) followed up to 20 years. The cohort will include women diagnosed from 1996 to 2010, and followed to 2015. Given the electronic medical records (EMR) at KPSC, we propose to conduct a prospective cohort study to follow women for CVD outcomes. In epidemiology, the cohort design is the strongest to measure disease occurrence. Thus, our aims are to: Aim 1: Examine the risk of new CVD events by endocrine drug use status (AI solely, tamoxifen [TAM] only; switchers (from TAM to AI); and non-users of endocrine treatment). Determine if the risks vary by important covariates such as race/ethnicity, body mass index, comorbidities, menopause status, and education/income levels. Potential interactions between AIs and tamoxifen with breast cancer therapies associated with increased CVD, including chemotherapy (e.g., anthracyclines, HER-2 targeted) or radiation therapy, will be examined. We will use standard methods of analysis for cohort. Aim 2: Estimate net benefit/risk indices for AIs versus tamoxifen that will inform clinical decision-making about the optimal treatment for post-menopausal women. In addition to the CVD outcomes, the risks will incorporate other adverse health effects of adjuvant treatment (e.g., endometrial cancer, pulmonary embolism, fractures, subsequent breast cancer). The net benefit/risk indices will be summarized in tables that can used by clinicians in the selection of AIs or tamoxifen for a particular patient.
 
 
 
 
 
 
 
 Innovative elements of the project:
 
 
 
 This innovative study presents the first real opportunity to determine whether women who take AIs are indeed at greater risk of CVD compared to women exposed to tamoxifen or no endocrine treatment. Innovative elements include: a timely question; demographically diverse cohort; large cohort size; long-term follow-up (up to 20 years); ability to follow women for outcomes via electronic medical records; and importantly, cost efficiency. Research studies that identify common drugs as important risk or protective factors in women with breast cancer are consistent with the CBCRP’s mission. None of the studies funded to date have examined the late side-effects of AIs.