Results of a new study published in Cancer Research show that the risk for an aggressive sub-type of breast cancer is increased in African American women with type 2 diabetes (T2D).
The study, led by Julie R. Palmer, MPH, ScD, from Boston University’s Slone Epidemiology Center in Boston, MA, used data from the Black Women’s Health Study (BWHS). This prospective cohort of 59,000 African American women have been followed biennially since 1995. During 847,934 person-years of follow-up, there were 1,851 new cases of invasive breast cancer reported, including 914 estrogen receptor (ER)-positive and 468 ER-negative cancers.
“The present analysis, from a large cohort of African American women, suggests that women with T2D have a 40% increased risk of developing ER-negative breast cancer,” the authors reported. “The association was observed primarily among women who were not obese. T2D was not associated with incidence of ER-positive breast cancer.”
Prior research has shown that diabetes is a risk factor for breast cancer, and African American women are disproportionately affected by T2D as well as ER-negative breast cancer. At the start of this study, baseline information such as weight (current and at age 18), height, information about births, lactation, physical activity, use of cigarettes or alcohol, years of education, diagnosis of T2D and medications used, along with other factors, were recorded.
After 20 years, 6,694 new cases of T2D were diagnosed—the prevalence of T2D in the BWHS cohort was 19%. Women with T2D were older, had a higher recent body mass index (BMI) and BMI at age 18, fewer years of education, earlier age at menarche, and less frequent vigorous physical activity than non-diabetic women.
A positive association with T2D was observed for ER-negative but not for ER-positive breast cancer, and the incidence of ER-negative cancer was evident at all stages.
With respect to the impact of medications to treat T2D, the hazard ratio (HR) was close to 1.0 regardless of medication use in women with ER-positive breast cancer. However, the HR for metformin users was 0.92, compared to 1.49 for medications other than metformin. In women with ER-negative breast cancer, the HR was 1.3 if treated, and 2.03 if untreated. The results did not differ by type of medication used.
Evaluation of HgA1c levels in a subset of 2,025 diabetic women who provided blood samples indicated that T2D was not well controlled in the group—only 38% of women had HgA1c levels below 6.5%. Among women who used diabetes medications, only 32% reported HgA1c levels below 6.5%.
Until recently, T2D primarily occurred in postmenopausal women, so previous case-control and cohort studies did not assess the relationship of T2D in premenopausal women. In this study, researchers found that a higher BMI was associated with increased risk of ER-positive breast cancer in postmenopausal women, but not in premenopausal women.
The investigators noted that this study was inspired by the concept of “metabolically healthy obesity.” They hypothesized that T2D may lead to an increased risk of breast cancer independent of obesity through mechanisms unrelated to steroid hormones, namely inflammation.
T2D was associated with a 92% increased risk of ER-negative breast cancer in non-obese women and a 55% increased risk for women with a waist-hip ratio 0.85. T2D did not correlate to increased risk of ER-positive breast cancer in any subgroup related to BMI or waist-hip ratio.
“Findings from the present study suggest that African American women with T2D are at increased risk of developing ER-negative breast cancer, and that poor metabolic health may be more important than BMI for ER-negative disease,” the authors concluded.
To read more about this study, click here.