Association of statin use with clinical outcomes in patients with triple-negative breast cancer.
Authors: Nowakowska Malgorzata , Lei Xiudong , Thompson Mikayla R , Shaitelman Simona Flora , Wehner Mackenzie , Woodward Wendy A. , Giordano Sharon H. , Nead Kevin Thomas 
Published: June 2021

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Background: Statins have been shown to target pathways related to breast cancer carcinogenesis, specifically in more aggressive breast cancer subtypes such as triple negative breast cancer (TNBC). Given the limited toxicity profile, low cost, and ease of use of statins, an association between statin therapy and improved breast cancer outcomes, particularly in aggressive breast cancers with more limited treatment options, could have important public health implications. Here we examine the association of statin therapy with breast cancer outcomes in women with stage I-III breast cancer, specifically TNBC. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry (TCR)-Medicare data. We included women age 66 years or older with histologically confirmed stage I-III breast cancer diagnosed from 2008-2015. We used multivariable Cox proportional hazards regression models to examine the association of statin use with overall survival (OS) and breast cancer specific survival (BCSS) adjusting for age, race, education, state buy-in, residence area, stage, subtype, endocrine therapy, radiation, chemotherapy, surgery, baseline statin use, comorbidity, and baseline hypertension. For BCSS, we accounted for the competing risk of death using the Fine and Grey method. We required all individuals to survive until 12 months post-diagnosis, which we defined as the start of the follow-up period, to account for immortal time bias. Results: We identified 45,063 patients with stage I-III breast cancer meeting inclusion criteria, out of which 22,518 (50.0%) received a statin within one year following diagnosis (statin-users). The 5-year cumulative estimates of breast cancer specific deaths were 5.9% and 6.9% for statin-users and non-users (P <.001), respectively. In the overall cohort, adjusted models showed a statistically significant association between statin use and improved BCSS (subdistribution hazard ratio [SHR], 0.82; 95% CI, 0.70 to 0.97; P =.021), but no association with OS (hazard ratio [HR], 0.96; 95% CI, 0.90 to 1.03; P =.23). The association was strongest in patients with TNBC for BCSS (SHR, 0.60; 95% CI, 0.42 to 0.86; P =.006) and OS (HR, 0.76; 95% CI, 0.61 to 0.95; P =.018). Stratification by stage showed that the effect of statin therapy in TNBC was limited to patients with localized disease. Our results were consistent using propensity score matched models and when limiting our analysis to statin therapy initiated following breast cancer diagnosis. Conclusions: Among women with non-metastatic breast cancer, we found that statin use was associated with an OS and BCSS benefit among women with TNBC. Our data suggest that statins may have a role as an adjuvant therapy in select patients with breast cancer and supports further investigation, particularly among patients with TNBC, for whom effective treatment options are more limited.