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

ABSTRACT: Multiple clinical trials investigate statins' effects in breast cancer. The ABCB1 genotype appears to influence statin response and toxicity in the cardiovascular setting. This exploratory study aimed to investigate the interplay between preoperative statin use, ABCB1 genotype, and tumor-specific expression of the statin target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in breast cancer. Preoperative statin use, ABCB1 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 (n = 80) was not associated with ABCB1 C3435T genotype (n = 576), HMGCR expression (n = 848), or clinical outcomes. ABCB1 C3435T TT-carriers had lower risk of breast cancer events than any C-carriers (adjusted hazard ratio (HRadj) 0.74; 95%CI 0.49, 1.12), but only in non-statin users (P interactio n = 0.042). Statin users with TT genotype had higher risk of distant metastasis (HRadj 4.37; 95%CI 1.20, 15.91; P interaction = 0.009) and shorter overall survival than other patients (HRadj 3.77; 95%CI 1.37, 10.39; P interactio n = 0.019). In conclusion, there were nominally significant interactions between ABCB1 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 ABCB1 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 ABCB1 genotype in breast cancer.

SUBMITTER: Tryggvadottir H

PROVIDER: S-EPMC6194198 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Tryggvadottir Helga H Huzell Louise L Gustbée Emma E Simonsson Maria M Markkula Andrea A Jirström Karin K Rose Carsten C Ingvar Christian C Borgquist Signe S Jernström Helena H

Frontiers in oncology 20181012

Multiple clinical trials investigate statins' effects in breast cancer. The ABCB1 genotype appears to influence statin response and toxicity in the cardiovascular setting. This exploratory study aimed to investigate the interplay between preoperative statin use, ABCB1 genotype, and tumor-specific expression of the statin target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in breast cancer. Preoperative statin use, ABCB1 C3435T genotype, and HMGCR expression in rel ...[more]

PMID: 30370250

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Project description:IntroductionStatins, HMG-CoA reductase inhibitors, are commonly used cholesterol-lowering medications which are also increasingly recognized to have anti-cancer properties for various cancers, including breast cancer. Most clinical evidence supports a protective effect of statin on reducing breast cancer recurrence, particularly in hormone-receptor positive breast cancers.This study seeks to study the impact of statin use on breast cancer recurrence in an Asian population.MethodsThis is a retrospective study of patients diagnosed with breast cancer at the National Cancer Centre and Singapore General Hospital from 2005-2015. Statin use was defined as use after surgery. Associations between statin use, breast cancer recurrence and overall survival were estimated using Cox proportional hazards regression with adjustment for age, TNM stage, grade, ER/HER2 status, and co-morbidities. Associations between statin-use and disease-specific survival were estimated using competing risks regression.ResultsA total of 7858 females with breast cancer were studied, 1353(17.2%) were statin users, 6505(82.8%) were non-statin users, with a median follow-up of 8.67 years. Distribution of cancer stage, histology, molecular subtypes and grades were similar in both groups. Estrogen receptor(ER) positive (HR 0.57,95%CI 0.43-0.76,p<0.001) and HER2 negative (HR 0.74,95%CI 0.57-0.96,p=0.026) invasive cancers had a lower risk of recurrence in statin users. Statin users trended towards a long term recurrence-risk reduction (all subtypes,HR 0.48,p=0.002; ER-, HR 0.34,p=0.036; HER2+,HR 0.10,p=0.002). The risk-reduction benefit is not appreciated in statin users with DCIS, possibly due to small recurrence event numbers. Disease-specific survival benefit was seen in statin users with ER+ cancers (adjusted SHR 0.71,95%CI 0.53-0.96,p=0.027), especially ER+ invasive cancers (adjusted SHR 0.72, 95%CI 0.53-0.97,p=0.028), but with no statistically significant benefit in overall survival for statin users (all subtypes).ConclusionThis is the first known retrospective study on the effect of statin use and breast cancer recurrence in an Asian population. Similar to previous international studies, statin use is associated with a risk reduction in breast cancer recurrence. This is especially beneficial in patients who have ER+ and HER2- invasive breast cancer. Statin use is also associated with a reduced risk of breast cancer recurrence in all subtypes of breast cancer in the long term (>6 years post diagnosis).

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

Publications

Interactions Between <i>ABCB1</i> Genotype and Preoperative Statin Use Impact Clinical Outcomes Among Breast Cancer Patients.

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