Clinical and genetic risk factors for bone loss in breast cancer survivors after adjuvant chemotherapy.

578 Background: Premature ovarian failure and accelerated bone loss are common late effects of adjuvant chemotherapy for breast cancer. Polymorphisms (SNPs) in bone metabolism and estrogen biosynthesis genes associated with osteoporosis in the general population have been identified (COL1A1 Sp1, IL6_634, VDR fok1 & taq1, ESR1_397, ESR1_325, ESR Xba1, TGF-B 509 & 869). Little is known about clinical and genetic risk factors for osteoporosis in breast cancer survivors.,We performed a cohort study at the Abramson Cancer Center of the University of Pennsylvania. Eligible patients were female, premenopausal at breast cancer diagnosis, AJCC stage I, II or III, had recent follow-up with no recurrence, and received adjuvant chemo one to four years prior to enrollment. Subjects signed informed consent, completed questionnaires, provided blood samples for genomic DNA, and underwent bone density measurement via DEXA scan as part of usual clinical care. Single nucleotide polymorphisms were identified via pyrosequencing and SNPlex assays.,We enrolled 132 breast cancer survivors with an average age at chemo start of 43 (range 26.7-57.8); 89% were Caucasian, 5% black. DEXAs were obtained on 118 (89%) at 1.9 years post-chemo (range 0-4.7). Most patients (94%) were treated with anthracycline-based regimens; 57% received a taxane. Hormone therapy was given to 76%; 12% received an aromatase inhibitor. Chemo-related amenorrhea occurred in 47% and was significantly associated with increasing age at chemo (p<0.0001). DEXAs were obtained at 41 facilities. Osteopenia/porosis (T-score < -1.0) at hip and/or spine occurred in 44 patients (33%). Increasing age at chemo was associated with a nonsignificant increase in the risk of osteopenia/porosis (OR 1.03, 95%CI 0.97, 1.1). Significant protective effects were found among women treated with a taxane (OR 0.45; 95%CI 0.21, 0.98), but dose density (q2 vs. q3wk) was not significant (OR 1.44, 95%CI 0.66, 3.2). SNP frequencies ranged from 16-96%; none were associated with osteopenia/porosis at this early timepoint.,Age, dose density, and presence of high-risk SNPs were not associated with osteopenia/porosis among breast cancer survivors in the early post-chemotherapy period. Taxanes may have a protective effect. No significant financial relationships to disclose.