Long-Term Metformin Use Linked to Fewer ER Positive Breast C
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Women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)-positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with T2D who received metformin, although case numbers were small.

The data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. Participants aged 35-74 years old were enrolled from all 50 US states and Puerto Rico in 2003-2009.

The analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had T2D, and another 5% developed new-onset T2D during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

Women with T2D who received metformin had a 14% lower rate of ER-positive breast cancer compared with women with diabetes not taking metformin, a non-significant association.
Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer compared with those who did not take it was 38%. In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a non-significant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

Researchers at National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina said, "Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer — but not other types of breast cancer — is biologically plausible and supported by our results even though some [endpoints] are not statistically significant."

"Clearly, this is an important area and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk," they added.