549 Background: Aromatase inhibitors (AI) are a gold standard adjuvant endocrine therapy for postmenopausal women with breast cancer. A number of randomized trials (RCTs) have reported modest improvements in breast cancer outcomes from extending treatment with AI beyond the initial 5 years after diagnosis. However, less in known about the toxicity of extended AI compared with no therapy. Methods: We conducted a systematic review of MEDLINE to identify RCTs that compared extended AI to placebo or no treatment. The search was supplemented by a review of abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meetings between 2013 and 2016. Odds ratios (ORs), 95% confidence intervals (CI), absolute risks, and the number needed to harm (NNH) associated with one adverse event were computed for prespecified safety and tolerability outcomes including cardiovascular disease, bone fractures, second cancers (excluding new breast cancer), treatment discontinuation due to adverse events and death without recurrence. Results: Seven trials comprising 16349 patients met the inclusion criteria. Longer treatment with AI was associated with increased odds of cardiovascular disease (OR = 1.18, 95% CI 1.00-1.40, P=0.05; NNH = 122) and bone fractures (OR = 1.34, 95% CI 1.16 - 1.55, P < 0.001; NNH = 72). Compared to control, longer AI therapy was associated with a higher odds of treatment discontinuation due to adverse events (OR = 1.45, 95% CI 1.25 - 1.68, P < 0.001; NNH = 20). Longer AI therapy did not influence the odds of second cancers (OR = 0.93, 95% CI 0.73-1.18, P = 0.56). There was a numerical excess of death without recurrence with longer AI therapy, but this was not statistically significant (OR = 1.11, 95% CI 0.9 - 1.36, P = 0.34). Conclusions: Longer durations of AI use are associated with increased cardiovascular events and bone fracture. There is a numerical, but non-statistically significant excess of deaths without breast cancer recurrence among patients receiving longer AI therapy. These data should be taken into account when considering extended adjuvant AI therapy for breast cancer patients.
Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study
