Abstract P6-10-04: Statins and breast cancer stage and mortality in the Women's Health Initiative cohort
Authors: Arun Monica P , Desai Pinkal , Lehman Amy , Kwan Marilyn L , Manson JoAnn E , Lavasani Sayeh , Wasswertheil-Smoller Sylvia , Sarto Gloria E , LeBoff Meryl S , Cauley Jane , Cote Michele L , Beebe-Dimmer Jennifer , Jay Allison , Chlebowski Rowan T , Simon Michael S 
Published: May 2015

Abstract
Background: Statins are the most widely prescribed cholesterol-lowering drugs in the United States, with approximately 25% of US adults using statins by 2008. The anti-carcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’ with statin users more likely diagnosed with early rather than late stage cancer. We evaluated the effects of statins on breast cancer stage migration and breast cancer-specific mortality in the Women’s Health Initiative (WHI) Clinical Trial and Observational Study. Methods: The study population included 128,675 postmenopausal women aged 50 to 79 years, with 7,883 newly-diagnosed pathologically-confirmed cases of in situ (19%), local stage (61%), regional stage (19%) and distant stage (1%) breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD=3.7) years of follow-up. To reduce the possibility of detection bias, we excluded women who did not report a mammogram within 5 years of study entry, and who had no health insurance or medical care provider (n=28,237). Stage was coded using criteria implemented in the Surveillance, Epidemiology and End Results Program and stratified into early stage (in situ and local) vs. late stage (regional and distant). Information on statin use prior to breast cancer diagnosis was collected at baseline and years one, three, six, and nine years post-baseline. Self- and interviewer-administered questionnaires were used to collect risk factor information. Cause of death was based on medical record review by physician adjudicators. Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) to evaluate the relationship between statin use as a time-dependent exposure and diagnosis of late stage breast cancer and breast cancer-specific mortality adjusting for important confounders. For these models, participants who had early stage breast cancer or who died during follow-up were censored at time of diagnosis or death, respectively. We also evaluated the effect of statins stratified by estrogen receptor (ER) status. Statistical tests were two-sided. Results: Statins were used by 10,474 women (8%) at baseline. In the multivariable-adjusted time-dependent model, statin use was associated with a marginal reduction in risk of late stage breast cancer (HR 0.84, 95% CI: 0.70-1.02, p=0.082) and a reduction in risk of late stage estrogen receptor positive breast cancer (HR 0.79, 95% CI: 0.63-0.99, p=0.044). Statin use was also associated with a marginal reduction in breast cancer-specific mortality although it did not reach statistical significance (HR 0.59, 95% CI: 0.32-1.06, p=0.075). Conclusions: In the WHI, statin use was associated with a modest reduction in risk of late stage estrogen positive breast cancer and a non-significant decrease in breast cancer mortality. We are currently performing sensitivity analyses on these models. Studies using other large data sets with longer follow-up and information on cancer-directed therapy are needed to further evaluate this possible association.
Citation Format: Monica P Arun, Pinkal Desai, Amy Lehman, Marilyn L Kwan, JoAnn E Manson, Sayeh Lavasani, Sylvia Wasswertheil-Smoller, Gloria E Sarto, Meryl S LeBoff, Jane Cauley, Michele L Cote, Jennifer Beebe-Dimmer, Allison Jay, Rowan T Chlebowski, Michael S Simon. Statins and breast cancer stage and mortality in the Women's Health Initiative cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-04.