Abstract P3-12-06: Statin use and outcome among breast cancer patients treated with neoadjuvant systemic chemotherapy

Abstract

BACKGROUND: Statins are cholesterol-reducing agents that affect intracellular pathways associated with tumorigenesis and inflammation. Preclinical studies have demonstrated that statins have anti-tumor effects and epidemiological studies have suggested that the use of HMG-CoA-reductase inhibitors is associated with improved long-term outcomes among breast cancer patients. In this study we sought to evaluate the effect of statins in the pathologic complete response (pCR) and survival outcomes among breast cancer patients receiving neoadjuvant systemic chemotherapy (NST). METHODS: Retrospective study including patients diagnosed between 1995-2007 with invasive primary breast cancer. All patients received neoadjuvant systemic chemotherapy. Use of statins during NST was identified by review of medical records. We compared pCR rate, relapse-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) between statin-users and non-users. pCR was defined as no evidence of invasive carcinoma in the breast and axillary lymph nodes at the time of surgery. Descriptive statistics and Cox proportional hazards model were used in the analyses. RESULTS: From the 1449 patients included, 74 (5.11%) were treated with statin during NST. Statin users were more likely to be older, overweight/obese and more likely to be also treated with beta-blockers or metformin. No differences in pCR were observed according to statin use (16.2% vs 17.6% p = 0.75). In the multivariable model, the use of statin was not an independent predictor of pCR. With 55 months of follow-up (415 recurrences and 359 deaths), the 5-year RFS was 82% in the statin-treated patients and 70% in the non-statin treated group (p = 0.03), no differences were seen in DSS or OS. Subset analyses according to tumor subtype demonstrated patients with hormone receptor-positive tumors treated with statins had better 5-year RFS (93% vs 76%; p = 0.01). In the multivariable model, no association was observed between statin use and outcome. CONCLUSIONS: In our cohort of patients, statin use during NST was not independently associated with pCR, RFS, DSS and OS. Further studies with larger number of statin-treated patients are warranted to clarify the role of HMG-CoA reductase inhibitors in the treatment of breast cancer patients. In addition future studies should evaluate the effect of prolonged statin use and take the different type of statin subtype into account. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-06.

Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta‐analysis

“…After exclusion of 737 results based on review of the title and abstract, 80 results were selected for full text review. After a review of full texts, 14 studies which met our inclusion criteria were identified and selected for data extraction and meta‐analysis . A flow diagram depicting our literature search strategy and study selection process is shown in Figure .…”

“…Upon exclusion of three conference abstracts, statin use continued to be related to improved RFS (7 studies, HR 0.68; 95% CI 0.56–0.82) and a similar trend towards improved overall survival (6 studies, HR 0.71; 0.46–1.09) and cancer‐specific survival (6 studies, HR 0.70; 95% CI 0.46–1.06).…”

“…The quality of the studies that were included in this systematic review was rated based on the standardized questionnaire in the Newcastle‐Ottawa scale for cohort studies. Study quality was high with the exception of three studies which was found to be of moderate quality . All three of these studies were limited by lack of adjustment for age or other key confounding variables such as estrogen receptor status.…”

“…Of the 14 studies included in this systematic review, data for recurrence‐free survival (RFS), cancer‐specific survival (CSS), and overall survival (OS) was reported in 10, 6 and 8 studies respectively. Outcomes for statin users were reported after adjustment for cancer stage and treatment in most studies; only three studies did not adjust the impact of statin use for cancer stage and treatment . In studies reporting cancer‐specific survival, the cause of death was confirmed by review of medical record in one study .…”

“…). Five‐year recurrence rates were extracted from six studies which reported them to calculate an absolute measure of risk reduction for recurrence . The absolute risk difference for recurrence conferred by any statin use was 0.12 (95% CI 0.05–0.19).…”