Breast cancer risk for women with diabetes and the impact of metformin: A meta‐analysis

Abstract

Background Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM). Methods Two separate meta‐analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021. Results A total of 30 and 15 studies were included in the first and second meta‐analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09–1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15–1.30) and 1.20 (95% CI, 1.05–1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60–1.12) for metformin users compared with nonmetformin users. Conclusions Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users. Impact These two meta‐analyses can inform decision‐making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.

Insulin Receptor Loss Impairs Mammary Tumorigenesis in Mice

“…The relationship between obesity, hyperinsulinemia, T2D, menopausal status and BC is complex 55,56 . While increased adiposity in postmenopausal women associates with an increase in BC risk, obesity and T2DM appear to have either no effect or even some protective effect in premenopausal women [57][58][59][60] . 1J-K), a feature found in >80% of human BC 18,19 .…”

Preexisting Diabetes and Breast Cancer Treatment Among Low-Income Women

“…Given that diabetes disproportionately affects low-income adults 37 and also increases the risk of breast cancer, 38 understanding the role of diabetes in adjuvant therapy for breast cancer among low-income women is critical to inform the appropriate care of this medically vulnerable patient population. In this population-based study, we comprehensively evaluated utilization, timely initiation, adherence, persistence and continuation, and/or completion of adjuvant therapies for breast cancer among Medicaid-insured women aged less than 65 years with and without diabetes.…”

Metformin and other anti‐diabetic medication use and breast cancer incidence in the Nurses' Health Studies

“…[5][6][7][8][9] However, the more recent literature is inconsistent, with more evidence suggesting there was no association between metformin use and breast cancer incidence. [10][11][12][13] More importantly, published studies have been conducted mainly in populations with T2D. Only three large epidemiological studies of breast cancer have included both non-T2D and T2D populations, 7,14,15 making the effect of metformin use in a general population and inter-relationship of T2D status and metformin difficult to estimate.…”

“…Several early epidemiologic studies (mostly before 2012) showed lower breast cancer incidence among metformin ever users compared with never users 5–9 . However, the more recent literature is inconsistent, with more evidence suggesting there was no association between metformin use and breast cancer incidence 10–13 . More importantly, published studies have been conducted mainly in populations with T2D.…”