Metformin Use Can Influence Breast Cancer Risk in Women with Type 2 Diabetes

Yong-Moon Park, MD, MS, PhD

A new study from the Annals of Oncology details links between metformin use and varying risk of developing different forms of breast cancer among women with type 2 diabetes.

Funded by the National Institutes of Health (NIH) and National Institutes of Environmental Health Sciences (NIEHS), results of the study indicate use of metformin lowered risk of ER-positive breast cancer but an increased risk of ER-negative breast cancer and triple-negative breast cancer (TNBC).

"Our study is the first to try to disentangle the effects of type 2 diabetes and the effects of metformin use. Having information about subtypes of breast cancer that may have different causes helped us to reach our conclusions,” said lead investigator Yong-Moon Mark Park, MD, MS, PhD, a postdoctoral fellow at the NIEHS and assistant professor at the University of Arkansas, in a statement. “However, it's important to note that some of our findings, especially for triple negative breast cancer, were based on a small number of cases and those results need replication.”

Thanks to previous research, clinicians have established a link between presence of type 2 diabetes and increased risk of developing breast cancer. However, use of metformin has been associated with reductions in multiple comorbid conditions. With this in mind, investigators sought to more thoroughly evaluate how use of the antidiabetes medication.

To do so, investigators obtained data from the Sister Study, which enrolled more than 50,000 women aged 35-74 years between 2003-2009. From the study, investigators identified 44,451 patients who met eligibility for inclusion in their study. Information related to type 2 diabetes use, use of antidiabetic medications, and covariates were obtained from baseline and follow-up questionnaires. For the purpose of analysis, incident breast cancer was identified through medical records.

From the cohort of 44,451 patients, investigators identified 3227 women with prevalent type 2 diabetes and 2389 with incident type 2 diabetes. Of those with type 2 diabetes, 3386 had received metformin monotherapy or combination therapy. During a follow-up period lasting a median of 8.6 years, which yielded 373,665 person-years of data, investigators identified 2678 primary breast cancer cases.

Upon analysis, investigators found there was no overall association between type 2 diabetes and breast cancer (HR, 0.99; 95% CI, 0.87-1.13), but type 2 diabetes was associated with an increased risk of TNBC (HR, 1.40; 95% CI, 0.90-2.16). In comparison to those without type 2 diabetes, metformin use was not associated with overall breast cancer risk but was associated with a decrease in risk of ER-positive breast cancer (HR, 0.86; 95% CI, 0.70-1.05) and increased risk of ER-negative (HR, 1.25; 95% CI, 0.84-1.88) and TNBC (HR, 1.74; 95% CI, 1.06=2.83). Investigators noted the inverse association with ER-positive cancer was stronger among those using metformin for 10 or more years (HR, 0.62; 95% CI, 0.38-1.01; P for trend =.09).

In an accompanying editorial, a pair of physicians from the University of Western Ontario and University of Toronto commend authors for their work and its valuable insight, but caution against over interpretation due to smaller sample sizes for specific cancer types.

"Despite the inclusion of 44,541 subjects, there were only 277 breast cancers diagnosed in women with T2D, including 25 TNBC; 177 and 20, respectively of these received metformin. The significant association of T2D with risk of TNBC in the subgroup treated with metformin (n=20) may have reflected chance and/or uncontrolled bias and confounding,” wrote Ana Lohmann, MD, PhD, of University of Western Ontario and Pamela Goodwin, MD, of the University of Toronto.

This study, “A prospective study of type 2 diabetes, metformin use, and risk of breast cancer,” was published in the Annals of Oncology.