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Statin use, HMGCR expression, and breast cancer survival - The Malmo Diet and Cancer Study.

ABSTRACT: Statins, commonly used to treat hypercholesterolemia, have also been proposed as anti-cancer agents. The identification of a predictive marker is essential. The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), which is inhibited by statins, might serve as such a marker. Thorough antibody validation was performed for four different HMGCR antibodies. Tumor expression of HMGCR (#AMAb90619, CL0260, Atlas Antibodies, Stockholm, Sweden) was evaluated in the Malmö Diet and Cancer Study breast cancer cohort. Statin use and cause of death data were retrieved from the Swedish Prescribed Drug Register and Swedish Death Registry, respectively. Breast cancer-specific mortality (BCM) according to statin use and HMGCR expression were analyzed using Cox regression models. Three-hundred-twelve of 910 breast cancer patients were prescribed statins; 74 patients before and 238 after their breast cancer diagnosis. HMGCR expression was assessable for 656 patients; 119 showed negative, 354 weak, and 184 moderate/strong expressions. HMGCR moderate/strong expression was associated with prognostically adverse tumor characteristics as higher histological grade, high Ki67, and ER negativity. HMGCR expression was not associated with BCM. Neither was statin use associated with BCM in our study. Among breast cancer patients on statins, no or weak HMGCR expression predicted favorable clinical outcome. These suggested associations need further testing in larger cohorts.

SUBMITTER: Bjarnadottir O

PROVIDER: S-EPMC6969108 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Statin use, HMGCR expression, and breast cancer survival - The Malmö Diet and Cancer Study.

Bjarnadottir Olöf O Feldt Maria M Inasu Maria M Bendahl Pär-Ola PO Elebro Karin K Kimbung Siker S Borgquist Signe S

Scientific reports 20200117 1

Statins, commonly used to treat hypercholesterolemia, have also been proposed as anti-cancer agents. The identification of a predictive marker is essential. The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), which is inhibited by statins, might serve as such a marker. Thorough antibody validation was performed for four different HMGCR antibodies. Tumor expression of HMGCR (#AMAb90619, CL0260, Atlas Antibodies, Stockholm, Sweden) was evaluated in the Malmö Diet and Cancer Study breast c ...[more]

PMID: 31953433

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Project description:ImportanceIn addition to protective effects on the cardiovascular system, statins may reduce the risk of breast cancer recurrence owing to potential anti-inflammatory benefits. Given that patients with breast cancer in Asia are relatively younger at diagnosis and most are free from traditional cardiovascular risk factors, it is uncertain whether the use of statins can improve survival.ObjectiveTo investigate the association of statin use with cancer- and noncancer-associated survival in patients with breast cancer.Design, setting and participantsThis cohort study used the Taiwanese National Health Insurance Research Database and National Cancer Registry to identify patients diagnosed with breast cancer from January 2012 to December 2017. Age, cancer stage, anticancer therapies, comorbidities, socioeconomic status, and cardiovascular drugs were matched by propensity score method. Statistical analyses, including Cox proportional hazards models, were performed from June 2022 to February 2023. The mean (SD) follow-up duration was 4.10 (2.96) years.InterventionsPatients receiving statins within 6 months before the diagnosis of breast cancer were compared with those not receiving statins.Main outcomes and measuresOutcomes included death, heart failure, and arterial and venous events.ResultsOverall, 7451 patients (mean [SD] age, 64.3 [9.4] years) treated with statins were matched with 7451 nonusers (mean [SD] age, 65.8 [10.8] years). Compared with nonusers, statin users had a significantly lower risk of all-cause death (adjusted hazard ratio [HR], 0.83; 95% CI, 0.77-0.91; P < .001). Notably, the risk reduction was mainly attributed to cancer-related death (adjusted HR, 0.83; 95% CI, 0.75-0.92; P < .001). Only a small number of patients died of cardiovascular causes, and the ratios were similar between statin users and nonusers. No significant differences were observed in cardiovascular outcomes, including heart failure and arterial and venous events, between statin users and nonusers. Using a time-dependent analysis, statin users also presented a significantly lower risk of cancer-related death (adjusted HR, 0.28; 95% CI, 0.24-0.32; P < .001) than nonusers, and notably, the risk was even lower in high-dose statin (HDS) users compared with non-HDS users (HDS users: adjusted HR, 0.84; 95% CI, 0.73-0.98; P = .002; non-HDS users: adjusted HR, 0.79; 95% CI, 0.68-0.91; P = 001).Conclusions and relevanceIn this cohort study of Asian patients with breast cancer, statin use was associated with a reduced risk of cancer-associated death rather than cardiovascular death. Our findings provide evidence to support the use of statins in patients with breast cancer; however, randomized studies are necessary.

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Statin use, HMGCR expression, and breast cancer survival - The Malmo Diet and Cancer Study.

Publications

Statin use, HMGCR expression, and breast cancer survival - The Malmö Diet and Cancer Study.

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