More favorable progesterone receptor phenotype of breast cancer in diabetics treated with metformin

Abstract

The coexistence of type 2 diabetes with breast cancer may result in poorer cancer-related survival due to a number of mediating factors including an alteration of tumor tissue hormonal sensitivity. Previous studies have shown that receptor status of breast tumors in diabetics may be changed; however, the mode of therapy for diabetes was usually ignored. This work presents the results of an analysis of the receptor status of breast carcinomas in 90 postmenopausal women suffering with diabetes mellitus type 2 who had been cured, for not less that 1 year prior to surgery, with different modes of antidiabetic therapy, including a dietary treatment only, sulfonylurea preparations, insulin therapy, and metformin as a monotherapy or in combination with sulfonylurea derivatives. No differences in estrogen receptors occurrence in tumor tissue were found in different treatment groups. The frequency of progesterone receptor-positive mammary carcinomas in women who were treated with metformin, irrespective of whether it was combined with sulfonylurea preparations, was significantly higher than in the sulfonylurea only group (P=0.043) and in the combined group of patients treated with either sulfonylurea or insulin (P=0.041). The exclusion of the patients who received neoadjuvant chemotherapy (24 persons) did not significantly affect the above results. The data may be used as an explanation of the distinctions in cancer characteristics and course between diabetic patients treated with either metformin or sulfonylurea derivatives and insulin.

Isolated and combined action of tamoxifen and metformin in wild-type, tamoxifen-resistant, and estrogen-deprived MCF-7 cells

“…Earlier we had published data suggesting that MF may be involved in the regulation of steroid receptor expression [26,35]. As shown in Table 2, we also found that MF mediated, although in a modest manner, differences in receptor expression.…”

“…Prior data from the first author's team (LMB) suggested that MF could alter PR levels [26,35]. Accordingly, we examined immunoblots of steroid receptors.…”

Metformin and Breast Cancer Stage at Diagnosis: A Population-Based Study

“…A smaller study of 90 women with diabetes and breast cancer reported an increased frequency of progesterone receptor-positive breast tumours among metformin users 16 . Finally, a study from the U.S. Women's Health Initiative found that metformin users were less likely to present with invasive breast cancer; however, the authors did not explore the relationship between metformin and breast cancer stage 15 .…”

“…Whether metformin affects molecular breast cancer subtype is controversial. One study reported a reduction in hormone-sensitive tumours with metformin exposure 15 ; others reported either an increase 16,17 or no difference in hormone-positive tumours 14 . Those prior studies have been limited by small sample sizes, incomplete drug data, and inconsistent comparator groups and statistical methods.…”

Metabolic Syndrome, Insulin Resistance, and Inflammation in Breast Cancer: Impact on Prognosis and Adjuvant Interventions

“…Hirsh et al [41] have recently suggested metformin may selectively target cancer stem cells, and that it may act synergistically with doxorubicin, a commonly used adjuvant therapy in breast cancer. One recent report examined characteristics of breast cancer developing in 90 postmenopausal women with diabetes receiving a variety of treatments [42]. Those receiving metformin were more likely to have progesterone receptor-positive breast cancers than those receiving sulfonylureas and/or insulin, suggesting metformin may influence the type of breast cancer that develops, at least in diabetic individuals.…”