Bisphosphonate Use and Risk of Recurrence, Second Primary Breast Cancer, and Breast Cancer Mortality in a Population-Based Cohort of Breast Cancer Patients

Studies of bisphosphonate use and breast cancer recurrence have produced conflicting results. Analyses of large adjuvant trials suggest that bisphosphonates reduce recurrence risk only in postmenopausal women. We assessed the effect of noncancer treatment-related bisphosphonate use on breast cancer outcomes in a population-based prognostic cohort of women with early-stage invasive breast cancer ( = 1,813; median follow-up = 11.8 years). Using medical record, interview, and cancer registry data, information was assembled on risk factors, cancer treatment, medication use, and outcomes. Statistical analyses used Cox proportional hazards regression models. Bisphosphonate use was associated with a significantly decreased risk of a breast cancer event [locoregional/distant recurrence or second primary breast cancer; HR ever use, 0.65; 95% confidence interval (CI), 0.47-0.90]. Reduced risks were observed in both pre/peri and postmenopausal women, in both ER-negative and ER-positive breast cancers, and for both earlier and later recurrences. Bisphosphonate use was also associated with a significantly decreased risk of breast cancer mortality (HR, 0.40; 95% CI, 0.23-0.69). Bisphosphonate use was associated with a reduction in risk of breast cancer events and improved breast cancer-specific survival in women with early-stage breast cancer. We hypothesize that the benefit of bisphosphonates on breast cancer outcomes may be present primarily in women with low bone density and regardless of menopausal status. Our findings suggest further consideration of bone density status as a modifier of bisphosphonate's potential beneficial benefits on breast cancer outcomes is warranted. .