AUTHOR=Tryggvadottir Helga , Huzell Louise , Gustbée Emma , Simonsson Maria , Markkula Andrea , Jirström Karin , Rose Carsten , Ingvar Christian , Borgquist Signe , Jernström Helena 

TITLE=Interactions Between ABCB1 Genotype and Preoperative Statin Use Impact Clinical Outcomes Among Breast Cancer Patients

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00428

DOI=10.3389/fonc.2018.00428

ISSN=2234-943X

ABSTRACT=<p>Multiple clinical trials investigate statins' effects in breast cancer. The <italic>ABCB1</italic> genotype appears to influence statin response and toxicity in the cardiovascular setting. This exploratory study aimed to investigate the interplay between preoperative statin use, <italic>ABCB1</italic> genotype, and tumor-specific expression of the statin target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in breast cancer. Preoperative statin use, <italic>ABCB1</italic> C3435T genotype, and HMGCR expression in relation to outcome were analyzed in 985 primary breast cancer patients from a population-based prospective cohort in Sweden from 2002 to 2012. Preoperative statin use (<italic>n</italic> = 80) was not associated with <italic>ABCB1</italic> C3435T genotype (<italic>n</italic> = 576), HMGCR expression (<italic>n</italic> = 848), or clinical outcomes. <italic>ABCB1</italic> C3435T TT-carriers had lower risk of breast cancer events than any C-carriers (adjusted hazard ratio (HR<sub>adj</sub>) 0.74; 95%CI 0.49, 1.12), but only in non-statin users (<italic>P</italic><sub><italic>interactio</italic></sub><sub>n</sub> = 0.042). Statin users with TT genotype had higher risk of distant metastasis (HR<sub>adj</sub> 4.37; 95%CI 1.20, 15.91; <italic>P</italic><sub><italic>interaction</italic></sub> = 0.009) and shorter overall survival than other patients (HR<sub>adj</sub> 3.77; 95%CI 1.37, 10.39; <italic>P</italic><sub><italic>interactio</italic></sub><sub>n</sub> = 0.019). In conclusion, there were nominally significant interactions between <italic>ABCB1</italic> genotype and preoperative statin use on clinical outcomes, while preoperative statin use was not associated with outcomes. Since this is an exploratory study of the impact of the <italic>ABCB1</italic> genotype in relation to statin use and clinical outcomes in the breast cancer setting, the results should be interpreted with caution and warrant replication in an independent cohort, preferably in a randomized setting. Since statin use is common in breast cancer patients, it would be of interest to further elucidate the clinical impact of the <italic>ABCB1</italic> genotype in breast cancer.</p>