Mortality and Recurrence Risk in Relation to the Use of Lipid-Lowering Drugs in a Prospective Breast Cancer Patient Cohort

Abstract

Lipid-lowering drugs are used for the prevention of cardiovascular diseases. Statins are the most commonly used lipid-lowering drugs. Evidence from preclinical and observational studies suggests that statins might improve the prognosis of breast cancer patients. We analyzed data from the German MARIEplus study, a large prospective population-based cohort of patients aged 50 and older, who were diagnosed with breast cancer between 2001 and 2005. For overall mortality, breast-cancer specific mortality, and non-breast-cancer mortality, we included 3189 patients with invasive breast cancer stage I–IV, and for recurrence risk 3024 patients with breast cancer stage I–III. We used Cox proportional hazards models to assess the association with self-reported lipid-lowering drug use at recruitment. We stratified by study region, tumor grade, and estrogen/progesterone receptor status, and adjusted for age, tumor size, nodal status, metastases (stage I–IV only), menopausal hormone treatment, mode of detection, radiotherapy, and smoking. Mortality analyses were additionally adjusted for cardiovascular disease, diabetes mellitus and body-mass index. During a median follow-up of 5.3 years, 404 of 3189 stage I–IV patients died, and 286 deaths were attributed to breast cancer. Self-reported use of lipid-lowering drugs was non-significantly associated with increased non-breast cancer mortality (Hazard ratio (HR) 1.49, 95% confidence interval (CI) 0.88–2.52) and increased overall mortality (HR 1.21, 95% CI 0.87–1.69) whereas no association with breast cancer-specific mortality was found (HR 1.04, 0.67–1.60). Restricted to stage I–III breast cancer patients, 387 recurrences occurred during a median follow-up of 5.4 years. We found lipid-lowering drug use to be non-significantly associated with a reduced risk of recurrence (HR 0.83, 95% CI 0.54–1.24) and of breast cancer-specific mortality (HR 0.89, 95% CI 0.52–1.49). Although compatible with previous findings of an improved prognosis associated with statin use, our results do not provide clear supportive evidence for an association with lipid-lowering drug use due to imprecise estimates.

Statins and risk of breast cancer recurrence.

“…Interestingly, in a study of 18,769 patients, benefit was observed only among females with ER-positive breast cancer, 26 in agreement with our results. Similarly, large population-based studies of patients with stage I-III breast cancer receiving lipidlowering regimens including statins confirmed a decreased risk of recurrence, 30 as well as lower overall cancer and breast cancer-specific mortality among statin users. 25 Studies suggest that the "statin effect" was stronger in tumors that were positive for hormone receptors.…”

The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis

“…This finding is consistent with virtually all previously reported data (cancer-specific mortality: HR 0.73, 95% CI 0.59-0.92, P = 0.000; all-cause mortality: HR 0.72, 95% CI 0.58-0.89, P = 0.000). In addition, many articles have confirmed that the use of statins can reduce breast cancer incidence and the risk of recurrence [13,14], thus indicating the wide-ranging protective effects of statins in patients with breast cancer. However, the mechanism for how statins improve the prognosis of patients with cancer differs from that in the cardiovascular field.…”

Statins and breast cancer prognosis: evidence and opportunities

“…Typically, a large body of preclinical data would be backed by numerous replicative observational studies demonstrating consistent associations in different populations. Presently, five observational studies support a protective effect of statins on breast cancer recurrence, 42,43,46,49,50 and these are reinforced by experimental studies of statin effects on breast tumour biomarkers. 36,37 The largest epidemiologic study of the association to date was nested in a nationwide Danish source population, from which more than 18,000 survivors were enrolled and followed for recurrence using the DBCG registry.…”

“…49 Key limitations of this study—which could readily account for its nearer-null association—include the investigators’ inability to isolate statin exposure from other antilipidaemic exposures, and their inclusion of former users in the unexposed comparison group.…”