A study published in the Annals of Oncology found that estrogen receptor (ER)-positive breast cancer risk was reduced in patients with type 2 diabetes who were taking metformin. However, metformin use was associated with an increased risk of ER-negative and triple-negative breast cancer.


Type 2 diabetes has been associated with an increased breast cancer risk, although commonly prescribed antidiabetic medications such as metformin may reduce that risk. Researchers assessed data from the prospective Sister Study that included women from the United States and Puerto Rico. A total of 44,541 participants aged 35 to 74 years at enrollment (2003-2009) were included in the present study and followed through September 15, 2017. Via baseline and follow-up questionnaires, researchers assessed time-varying, self-reported, physician-diagnosed prevalent and incident type 2 diabetes; use of antidiabetic medications; and covariates.


During a median follow-up of 8.6 years, 2,678 cases of breast cancer were diagnosed at least one year after enrollment. The cohort included 3,227 women (7.2%) with prevalent and 2,389 (5.3%) with incident type 2 diabetes, of whom 61% (n=3,386) were ever treated with metformin monotherapy or combination. Women with type 2 diabetes were older, had a higher enrollment-measured body mass index (BMI) and self-reported BMI at 30 to 39 years, less physical activity, lower-quality diet, and shorter lifetime duration of breastfeeding than women without diabetes.


There was no overall association between type 2 diabetes and breast cancer risk (hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.87-1.13). However, type 2 diabetes was associated with an increased risk for triple-negative breast cancer (HR, 1.40; 95% CI, 0.90-2.16). “This suggests that ER-positive and ER-negative breast cancer involve different mechanisms,” the researchers noted.


Compared with those without diabetes, metformin use for type 2 diabetes was not associated with overall breast cancer risk (HR, 0.98; 95% CI, 0.83-1.15), but 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 (HR, 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR, 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive breast cancer was stronger for longer duration (defined as ≥10 year) of metformin use (HR, 0.62; 95% CI, 0.38-1.01; P=0.09).


“Our findings provide evidence that type 2 diabetes and use of metformin may be associated with breast cancer differentially by hormone receptor status,” the researchers concluded.


Link: https://www.annalsofoncology.org/article/S0923-7534(20)43214-4/fulltext