Bone density (BMD) loss is a consequence of aromatase inhibitors (AI) treatment of breast cancer. B-ABLE cohort includes 391 postmenopausal women with early breast cancer starting AI therapy. Participants experienced a 1.98% (95% CI 1.542.42% P<0.0001) bone loss at lumbar spine (LS) and 1.24% (95% CI 0.811.67% P<0.0001) bone loss at femoral neck (FN) after 1 year on AI therapy and a 3.51% (95% CI 3.004.03% P<0.0001) bone loss at LS and 2.07% (95% CI 1.512.63% P<0.0001) bone loss at FN after 2 years. We aim to identify genetic variants associated with BMD loss during AI therapy.
Single nucleotide polymorphisms (SNPs) in genes involved in vitamin D and estrogen pathways were genotyped in the B-ABLE cohort. Multivariate linear regression was performed to test the association between SNPs and LS and FN BMD loss after 1 and 2 years of follow-up. All models were adjusted for age, BMI, tamoxifen, chemotherapy, 25(OH)-VITD and type of AI. P<0.05 was considered nominally significant.
Two SNPs in CYP11A1 (rs2959008 and rs7174179) were associated with FN BMD loss at 1 (P=0.003 and P=0.012) and 2 years (P=0.004 and P=0.002). For LS BMD loss, SNPs in HSD3B2 (rs2854964), CYP2C19 (rs12248560) and CYP2C9 (rs28371674) were associated at 1 year of follow-up (P=0.026, P=0.019 and P=0.011 respectively). The rs12248560 remained significant at 2 years (P=0.014).
The rs11907350 in CYP24A1 was associated with FN BMD loss at 1 year. For LS BMD loss, one SNP in GC (rs11907350) at 1 year (P=0.020) and one in VDR (rs2544037) at 2 years (P=0.024) reached significant P-values. Only the rs7174179 in CYP11A1 for FN BMD loss association at 2 years remained significant after Bonferroni correction.
Conclusion: Several genes in estrogen and vitamin D signaling appeared involved in BMD loss in AI-treated women, suggesting a complex regulation of this outcome.
17 May 2014 - 20 May 2014