Statin use and risk of breast cancer recurrence in a prospective cohort study.

B214

Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] inhibitors) are widely prescribed cholesterol-lowering agents that have been shown in large randomized controlled trials to reduce the risk of cardiovascular disease. Laboratory studies have demonstrated the ability of statins to induce apoptosis and inhibit tumor growth, particularly in colorectal and breast cancer models. However, observational studies have yielded mixed results about the possible chemopreventive effects of statins on breast cancer risk. With over two million breast cancer survivors in the US today, no studies to date have evaluated the effect of statins on breast cancer survivorship. We examined the association between any statin use (yes vs. no and duration) and breast cancer recurrence in a prospective cohort of 1944 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average 2 years post-diagnosis. Information on statin and nonstatin lipid-lowering agents such as generic name, date dispensed, and days supply were obtained from the KPNC pharmacy database while relevant demographic and tumor characteristic information was collected from a mailed questionnaire and the KPNC Cancer Registry, respectively. Health outcomes were ascertained every 6 months by mailed questionnaire and verified by medical record. Recurrence events included local, regional, and distant disease, new contralateral breast cancers, and breast cancer deaths if no previous recurrence was recorded. A total of 217 breast recurrences were confirmed as of September 14, 2006. Delayed entry Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI), adjusting for age, cancer stage, tamoxifen treatment, race, and body mass index. Person-years were calculated for each subject, ranging from date of cohort entry to date of first confirmed cancer recurrence event, date of non-breast cancer death, drop-out date, or September 14, 2006, whichever occurred first. Any use of statins was associated with a statistically significant decreased risk of breast cancer recurrence (RR = 0.50; 95% CI: 0.34-0.74). Among the statins, lovastatin was primarily prescribed (89%) and was indicative of a statistically significant reduced risk (RR = 0.52 (0.35-0.78). A significant trend in risk by increasing duration of statin use was apparent (p<0.001). Hydrophilic statins were not prescribed by the KPNC pharmacy and thus could not be adequately examined in relation to breast cancer recurrence. No significant association was found for use of any nonstatin lipid-lowering agent including niacin and genfibrozil (RR = 0.80; 95% CI: 0.40-1.57). Our findings provide strong support for a protective effect of hydrophobic statins on risk of breast cancer recurrence.