Type 2 diabetes in women appears to be associated with an increased risk of ER- and triple negative breast cancer but a decreased risk of ER+ breast cancer.
A study of 44,541 women from the US and Puerto Rico Sister Study – sisters or half sisters of women with breast cancer – found type 2 diabetes was associated with a 40% increased risk of TNBC (HR 1.40) and a 25% increased risk of developing ER-negative breast cancer (HR 1.25) when compared with women who did not have diabetes.
However overall, there was no association between type 2 diabetes and the risk of developing breast cancer (HR 0.98).
The prospective study, published in Annals of Oncology, said the findings of a small decreased risk in ER+ breast cancer (HR 0.86) might be related to use of metformin.
“This may be explained in part by the observed inverse association between long-term metformin use for T2D and the more common ER+ breast cancer. It is possible that long-term use of metformin has reduced any risk of breast cancer associated with T2D,” the study said.
The researchers also observed a positive association between breast cancer risk and incident T2D with non-metformin antidiabetic medication use.
“Considering that metformin is now a first-line treatment of T2D, those using other antidiabetic medications may have had more severe disease or been treated with insulin, which has been suggested to increase risk of breast cancer.”
“This finding may be aligned with our finding of no association between untreated T2D and ER+ breast cancer, but could be due to those women having less severe disease.”
The study also found a possible inverse association between type 2 diabetes and premenopausal breast cancer, but no association with postmenopausal disease.
An accompanying editorial said the evidence linking type 2 diabetes, metformin use and breast cancer subtypes was inconsistent and definitive conclusions were not yet possible.
They added that the Sister Study also had some limitations such as the small number of breast cancers (n=277) which developed in women with diabetes.
“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.”
“Clearly, this is an important area and additional research is needed to untangle the web of inter-related associations of T2D, its treatment and BC risk.”
“Given the widespread use of metformin to treat T2D and the need for large sample sizes to examine BC subgroup associations, this research will be challenging.”