Low-dose aspirin, statins, and metformin and survival in patients with breast cancers: a Norwegian population-based cohort study

Abstract

Background Previous studies assessed the prognostic effect of aspirin, statins, and metformin in breast cancer (BC) patients, with inconclusive results. Methods We performed a nationwide population-based cohort study to evaluate if post-diagnostic use of low-dose aspirin, statins, and metformin was associated with BC-specific survival. Women aged ≥ 50 years and diagnosed with BC in 2004–2017, who survived ≥ 12 months after diagnosis (follow-up started 12 months after diagnosis), were identified in the Cancer Registry of Norway. The Norwegian Prescription Database provided information on prescriptions. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between post-diagnostic use and BC-specific survival, overall and by oestrogen receptor (ER) status. Results A total of 26,190 patients were included. Of these, 5324 (20%), 7591 (29%), and 1495 (6%) were post-diagnostic users of low-dose aspirin, statins, and metformin, respectively. The median follow-up was 6.1 years, and 2169 (8%) patients died from BC. HRs for use, compared to no use, were estimated at 0.96 (95% CI 0.85–1.08) for low-dose aspirin (ER+: HR = 0.97, 95% CI 0.83–1.13; ER−: HR = 0.97, 95% CI 0.73–1.29, p value for interaction = 0.562), 0.84 (95% CI 0.75–0.94) for statins (ER+: HR = 0.95, 95% CI 0.82–1.09; ER−: HR = 0.77, 95% CI 0.60–1.00, p value for interaction = 0.259), and 0.70 (95% CI 0.51–0.96) for metformin (compared to use of non-metformin antidiabetics) (ER+: HR = 0.67, 95% CI 0.45–1.01; ER−: HR = 1.62, 95% CI 0.72–3.62, p value for interaction = 0.077). Conclusion We found evidence supporting an association between post-diagnostic use of statins and metformin and survival, in patients with BC. Our findings indicate potential differences according to ER status.

Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies

“…One study in patients with type 2 diabetes that evaluated different cancers did not find that effect of metformin on overall cancer risk; however, when they evaluated different cancers separately, they did observe a modest reduction in breast cancer with an incidence rate ratio of 0.77 (95% CI:0.43; 1.40) [ 91 ]. The use of metformin after a cancer diagnosis has also been shown to decrease the risk of breast cancer-specific death [ 92 ]. An early meta-analysis of observational studies found that metformin decreased breast cancer risk in postmenopausal women with diabetes compared to those on other antidiabetic therapies [ 11 ].…”

Metformin: From Diabetes to Cancer—Unveiling Molecular Mechanisms and Therapeutic Strategies

“…Significantly, several observational studies have consistently shown a decreased risk of breast cancer and lower recurrence rates among individuals who are overweight and/or have T2DM and use metformin [122,123]. Metformin emerges as a significant player associated with improved disease-free survival (DFS) and overall survival (OS), suggesting its potential positive impact on survival outcomes among invasive breast cancer patients with T2DM [124]. In addition, a meta-analysis of 31,031 breast cancer patients suggests a potential benefit of metformin therapy, showing reductions in all-cause mortality and progression-free survival compared with non-metformin users [125].…”