Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes

Abstract

We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64–1.31) or ILC (HR 0.68, 95% CI 0.32–1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45–0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64–2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62–0.96) and ILC patients (HR 0.59, 95% CI 0.37–0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67–0.96) and in ILC patients (HR 0.66, 95% CI 0.43–1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.

Association of Statin Use With Cancer- and Noncancer-Associated Survival Among Patients With Breast Cancer in Asia

“…On the other hand, statins have received special attention for their pleiotropic effects, including anti-inflammatory and antitumor potential . A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for the anticancer effects of statins is inconsistent . In a cohort of 3165 women with breast cancer, statin use was consistently associated with reduced mortality.…”

“… 4 , 5 , 6 A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for the anticancer effects of statins is inconsistent. 4 , 5 , 6 , 17 In a cohort of 3165 women with breast cancer, 17 statin use was consistently associated with reduced mortality. In a retrospective analysis of 748 patients with non–small cell lung cancer, Atkins et al 18 reported statin use as an independent predictor of all-cause death.…”

Screening of GPCR drugs for repurposing in breast cancer

“…Patients were categorized into mutually exclusive and collectively exhaustive cohorts based on the type of β-blocker they used. Covariates like age, sex, race, ethnicity, BC as the first cancer, stage of BC, subtype of BC, use of statins due to their effects on BC mortality ( Lv et al, 2020 ; Hosio et al, 2021 ; Kim et al, 2022 ; Zhao et al, 2022 ), Charlson comorbidity index, and the year of BC diagnosis were measured. The all-cause mortality and BC mortality were the outcomes for this study, and patients were followed from incident BC diagnosis until the earliest of all-cause mortality, discontinuation of the index β-blocker, switching or concomitant use of comparator β-blockers, or the end of the study period (31 December 2015).…”

Metformin and Breast Cancer: Where Are We Now?

“…An ongoing trial (NCT01302379) is evaluating the impact of lifestyle control or diet plus metformin or placebo in nondiabetic patients with breast cancer history. The combination of metformin with therapies targeting other metabolic syndrome factors, such as statins, could enhance metformin’s antitumoral properties [ 134 ]. This is the primary objective of the so-called METRICS trial (NCT02201381), designed to evaluate the safety, tolerability, and efficacy of metabolic combination treatments including metformin, atorvastatin, doxycycline, and mebendazole in breast cancer.…”