Impact of Statin Use on Outcomes in Triple-Negative Breast Cancer

Abstract

Purpose: We sought to investigate if the use of HMG Co-A reductase inhibitors (statins) has an impact on outcomes among patients with triple negative breast cancer (TNBC). Methods: We reviewed the cases of women with invasive, non-metastatic TNBC, diagnosed 1997-2012. Clinical outcomes were compared based on statin use (defined as ever use during treatment vs. never use). We identified a subset of women for whom a 5-value lipid panel (5VLP) was available, including total cholesterol, low density lipoprotein, high density lipoprotein, very low density lipoprotein, and triglycerides. The Kaplan-Meier method was used to estimate median overall survival (OS), distant metastases-free survival (DMFS), and local-regional recurrence-free survival (LRRFS). A Cox proportional hazards regression model was used to test the statistical significance of prognostic factors. Results: 869 women were identified who met inclusion criteria, with a median follow-up time of 75.1 months (range 2.4-228.9 months). 293 (33.7%) patients used statins and 368 (42.3%) had a 5VLP. OS, DMFS, and LRRFS were not significant based on statin use or type. Controlling for the 5VLP values, on multivariable analysis, statin use was significantly associated with OS (HR 0.10, 95% CI 0.01-0.76), but not with DMFS (HR 0.14, 95% CI 0.01-1.40) nor LRRFS (HR 0.10 95% CI 0.00-3.51). Conclusions: Statin use among patients with TNBC is not associated with improved OS, although it may have a benefit for a subset of patients. Prospective assessment would be valuable to better assess the potential complex correlation between clinical outcome, lipid levels, and statin use.

Association of statin use with clinical outcomes in patients with triple‐negative breast cancer

“…The magnitude of effect reported in that study was similar to what we observed in our analysis, although their findings were likely limited by low power. 32 An association between statins and improved outcomes in patients with breast cancer is biologically plausible. Statins inhibit HMG-CoA reductase (HMGCR), the rate-limiting step in the mevalonate pathway, which is upregulated by mutations in TP53 in breast cancer, including the majority of triple-negative tumors.…”

Simvastatin treatment varies the radiation response of human breast cells in 2D or 3D culture

“…It was also detected that MCF-7 cells, which are ER + , were not so strongly affected, like MDA-MB231 cells, as the representative for triple negative breast cancer [34]. But their experimental data is contrary to the epidemiological data from Shaitelman et al (2017) [12] which showed no effect of statins in the cohort of triple negative breast cancer patients. MCF7 (2D) MCF7 (3D) Fig.…”

“…Epidemiological studies show that the receptor status of patients play an important role for the effectiveness of SVA. Because statin use is not associated with an improved overall survival of triple negative breast cancer patients [12], but a small subset of patients with ER + tumours benefit from the use of statins [7]. It was also detected that MCF-7 cells, which are ER + , were not so strongly affected, like MDA-MB231 cells, as the representative for triple negative breast cancer [34].…”

“…Owing to its beneficial efforts for breast cancer patients, it was supported as a component of adjuvant therapy [10]. But, in fact, not all tumour entities are equally sensitive to statins, there are also studies that found no beneficial effect of them in a colon cancer cohort [11] and for triple negative breast cancer patients [12].…”

Disrupting Cholesterol-FOXO3-KRT14 axis suppresses metastasis of triple-negative breast cancer

“…Among the various subtypes of apolipoproteins, apolipoprotein A1 (ApoA1) plays a pivotal role in cholesterol efflux by binding to cellular membrane-bound receptors, including ABCA1 and ABCG1 13 . Several previous studies employed statins, the intensive inhibitors of cholesterol biosynthesis, for breast cancer treatment; however, the beneficial effects are still inconclusive in TNBC [14][15][16] . There is an urgent need to develop more effective therapeutics to manipulate aberrant cholesterol in TNBC.…”