While type 2 diabetes (T2D) has been associated with an increased risk of breast cancer, a recent study found that extended use of the diabetes treatment metformin can help reduce that risk for some patients. 

According to findings published in the Annals of Oncology, metformin could help reduce the risk of patients developing breast cancer “by improving insulin sensitivity and correcting hyperinsulinemia through reduction of circulating insulin and insulin-like growth factor concentrations.” The authors said the treatment could also constrain the cancer growth by activating adenosine monophosphate-activated protein kinase and the inhibition of the mammalian target of rapamycin signaling pathway. They noted that, conversely, insulin treatment could increase the risk of patients developing breast cancer. 

The retrospective study looked at data for more than 40,000 patients in the Sister Study. The patients were all between the ages of 35 and 74 at the time of enrollment and met certain eligibility criteria, including prevalent and incident type 2 diabetes and the use of antidiabetic medications. The women evaluated had no previous breast cancer diagnosis but were sisters or half-sisters of women who had been previously diagnosed. According to their findings, during a median follow-up of 8.6 years, 2,678 breast cancers were diagnosed at least one year after enrollment. The authors noted that 7.2% of patients had prevalent T2D while 5.3% had incident diabetes. Of those patients, 61% had been treated with metformin. 

While there was no overall association found between T2D and breast cancer risk (HR = 0.99; 95% CI, 0.87-1.13), the authors said T2D was associated with an increased risk of triple-negative breast cancer (HR = 1.40; 95% CI, 0.90-2.16). Compared to patients who did not have T2D, the authors noted those who had diabetes and were treated with metformin showed no association with overall breast cancer risk (HR = 0.98; 95% CI, 0.83-1.15). However, it was associated with a decreased risk of ER-positive breast cancer (HR = 0.86; 95% CI, 0.70-1.05) and an increased risk of ER negative breast cancer (HR = 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR = 1.74; 95% CI, 1.06-2.83). An inverse association was observed with ER-positive cancer for patients who took metformin for more than 10 years (HR = 0.62; 95% CI, 0.38-1.01; P for trend = 0.09), with results supported by “sensitivity analyses.” 

“It is possible that long-term use of metformin has reduced any risk of breast cancer associated with T2D,” the authors said. “While this may be true for ER+ breast cancer, T2D with metformin use was in fact positively associated with ER- breast cancer and TNBC as was incident T2D treated with other medications.”

The authors said their findings could suggest that ER+ and ER- breast cancer involve different mechanisms or that metformin could influence the evolution of a tumor, preventing the expression of ERs. 

While acknowledging the possibility that patients with T2D are screened more for breast cancer due to more frequent appointments with their providers, the authors said since more than 80% of the participants in the study had reported a mammogram within a year of the start of the study the detection bias was deemed to not be substantial.