New-onset osteopenia/osteoporosis among long-term survivors of breast cancer: Role of hormone therapies and metabolic risk factors.

12046 Background: Anti-cancer therapies (including aromatase inhibitors [AIs]) and metabolic risk factors are known to result in bone mineral density (BMD) loss in breast cancer survivors (BCS). There is limited information regarding the very long-term risk of new-onset osteopenia/osteoporosis among BCS and the associated risk factors. Methods: Patients who survived ≥1y after BC underwent q2y dual x-ray absorptiometry (DXA) screening at a single center; those exposed to bisphosphonates or with osteopenia/osteoporosis prior to BC were excluded. All DXAs from BC diagnosis to diagnosis of osteopenia/osteoporosis were processed in Python via automated analysis. New-onset osteopenia/osteoporosis was defined as a DXA with a T-Score < -1 at any bone site. Demographics, treatment exposures, and metabolic risk factors were abstracted from medical records. Cumulative incidence described the risk of osteopenia/osteoporosis, and Cox proportional hazards models described the risk factors, treating therapeutic exposures as time-varying variables. Multivariable linear regression models with generalized estimation equations assessed longitudinal trend of BMD prior to onset of osteopenia/osteoporosis. Results: We evaluated 4,575 DXAs in 1,267 BCS (median age at BC: 55y; median follow-up: 9.8y; non-Hispanic Black: 28.6%). Overall, 39.2% received AIs, 18.7% received selective estrogen receptor modulators (SERMs), 20.1% received AIs & SERMs, and 21.9% received neither. The cumulative incidence of osteopenia/osteoporosis in the entire cohort was 19% at 2y, increasing to 42% at 5y and 68% at 15y after BC. In those exposed to AIs, the cumulative incidence of osteopenia/osteoporosis was 38%, 75%, and 96% at 2y, 5y, and 15y, respectively. Multivariable analysis revealed the following to be independently associated with osteopenia/osteoporosis: AIs (HR = 1.94, 95%CI = 1.61-2.34), increasing age: (HR = 1.03, 95%CI = 1.02-1.04), pre-BC dyslipidemia (HR = 1.36, 95%CI = 1.06-1.75), and post-BC dyslipidemia (HR = 1.47, 95%CI = 1.19-1.81). Black race (HR = 0.44, 95%CI = 0.36-0.54, ref = white race), pre-cancer obesity (HR = 0.71, 95%CI = 0.56-0.91), and post-cancer obesity (HR = 0.79, 95%CI = 0.65-0.96) were protective. Exposure to SERMS was not a risk factor (HR = 0.97, 95%CI = 0.76-1.23). Among those exposed to AIs, radial wrist BMD declined significantly more steeply among those who eventually developed osteoporosis/osteopenia (0.45%/year), when compared with those who did not (0.11%/year) (p = 0.04). Conclusions: These results provide evidence for close surveillance of BC survivors at increased risk of osteopenia/osteoporosis for extended periods, and aggressive management of dyslipidemia before, during and after BC.