Abstract 1838: Lipophilic statin use and risk of breast cancer subtypes

Abstract

Abstract Background: Preclinical studies suggest that lipophilic statins have anti-cancer properties and that hormone receptor (HR)-negative breast cancer is the most responsive subtype. Kumar et al. (2008) reported that patients with HR-negative cancers were less likely to have used lipophilic statins than patients with HR-positive disease. However, this study within Kaiser Permanente Northern California (KPNC) included only cases diagnosed in 2003 and, because of its case-only design, was unable to make risk inferences. We conducted a large case-control study spanning 11 years within KPNC to investigate whether lipophilic statin use is associated with: (1) decreased risk of HR-negative breast cancer, (2) increased risk of HR-positive breast cancer or (3) both. Furthermore, we investigated whether lipophilic statin use is associated with the risk of the intrinsic breast cancer subtypes and attempted to replicate Kumar et al.'s results. Methods: We identified 22,486 cases with invasive breast cancer of known HR-status diagnosed at KPNC from 1997 to 2007. Controls were individually matched to cases at a ratio of 10:1, based on year of birth and KPNC pharmacy coverage. Use of the lipophilic statins, oral contraceptives (OC) and menopausal hormones (HT) was ascertained via KPNC's electronic pharmacy records. Case-control odds ratios (OR) were adjusted for age, pharmacy coverage, OC and HT use; case-only ORs were additionally adjusted for race. We performed an external adjustment for the unmeasured confounders obesity and alcohol use. Results: We found no association between lipophilic statin use (≥ 2 years vs. never) and overall breast cancer risk (OR=1.02; 95% CI=0.97-1.08; p=0.42). Lipophilic statin users did not have a decreased risk of HR-negative breast cancer (OR=0.98; 95% CI=0.84 −1.14; p=0.74), or an increased risk of HR-positive disease (OR=1.03; 95% CI=0.97-1.10; p=0.31). Lipophilic statin use was not associated with risk of any of the intrinsic breast cancer subtypes, luminal A, luminal B, HER2+/ER- and triple negative. In case-only analysis including all 11 years, HR-negative cases had slightly lower odds of being lipophilic statins users (OR=0.91; 95% CI=0.78-1.05; p=0.18), however, this result was not statistically significant. We were able to replicate Kumar et al.'s findings for 2003, which was the only year in the 11-year study period with a statistically significantly lower proportion of HR-negative cases among statin users, and thus, likely a stochastic outlier. Conclusions: Our results do not support an association between lipophilic statin use and breast cancer risk in general or the risk of ER, PR and HER2-defined subtypes specifically. Any effect, if it exists at all, is likely much smaller than previous studies suggested. These findings should be considered in the interpretation of several ongoing breast cancer chemoprevention trials of lipophilic statins as well as in the planning of future interventional studies using statins. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1838.