Breast cancer is the most commonly diagnosed cancer among women and the second leading cause of cancer related deaths. Nevertheless, most women with breast cancer are diagnosed with early-stage disease, and their risk of dying of cancer is lower than their risk of dying of other causes. Because prognosis for these women is so good, the choices of treatments are particularly important, because side effects and complications of treatments may impact overall health status more than the breast cancer itself. Recently, randomized controlled trials identifying substantial benefits of aromatase inhibitors for early- stage cancers have led to national recommendations that every postmenopausal woman with an estrogen receptor-positive breast cancer and no contraindications be treated with an aromatase inhibitor at some point in her adjuvant course. Nevertheless, these drugs may have adverse effects. Clinical trials have identified increases in fracture rates, and some studies have demonstrated a non-significant increase in non-breast cancer deaths in patients taking aromatase inhibitors compared to women on tamoxifen or placebo, suggesting that the drugs may impact the risk of death from other causes, such as cardiovascular disease. Using administrative data from HealthCore, an independent subsidiary of WellPoint, Inc, we will explore whether the use of aromatase inhibitors in community-based populations of early-stage breast cancer patients aged 51 is associated with an increased incidence of cardiovascular events and fracture. In addition, we will examine whether women treated with aromatase inhibitors are receiving recommended bone density testing. Comparison groups will include women with breast cancer treated with tamoxifen only, tamoxifen followed by aromatase inhibitors, no hormonal therapy, and closely-matched women with no history of breast cancer. Specifically, we will: 1. Assess whether aromatase inhibitor therapy is associated with increased risk of myocardial infarction, stroke, and fracture outside of the clinical trial setting. 2. Identify subgroups of women who have more or less favorable risk of cardiovascular disease and fracture while on aromatase inhibitor therapy. 3. Assess whether women who are being treated with aromatase inhibitors are receiving recommended bone density testing. Project Narrative/Relevance: Aromatase inhibitors are currently being used widely as an adjuvant treatment for breast cancer, and understanding better the potential risks associated with this therapy and how these risks differ by patient characteristics will help physicians and patients weigh potential benefits and risks when decisions about use of this therapy are being made. In addition, information about potential harms of this therapy may lead to strategies to reduce risk and decrease non-cancer mortality for women who are treated with aromatase inhibitors.

Public Health Relevance

Finally, understanding whether women treated with aromatase inhibitors are receiving recommended bone density testing will help identify whether new strategies are needed to improve testing to identify drug-induced bone loss. ? ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Health Services Organization and Delivery Study Section (HSOD)
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Warren, Joan
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Harvard University
Schools of Medicine
United States
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Saylor, Philip J; Smith, Matthew R; O'Malley, A James et al. (2014) Androgen-deprivation therapy and risk for biliary disease in men with prostate cancer. Eur Urol 65:642-9
Ligibel, Jennifer A; James O'Malley, A; Fisher, Maxine et al. (2012) Risk of myocardial infarction, stroke, and fracture in a cohort of community-based breast cancer patients. Breast Cancer Res Treat 131:589-97
Ligibel, Jennifer A; O'Malley, A James; Fisher, Maxine et al. (2012) Patterns of bone density evaluation in a community population treated with aromatase inhibitors. Breast Cancer Res Treat 134:1305-13