Metformin Use to Reduce Disparities in Newly Diagnosed Breast Cancer

Breast cancer is one of the most common malignancies in women globally, with \~1.4 million new cases diagnosed annually Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. While diabetes/insulin-resistance and breast cancer are distinct diseases, insulin-signaling plays a central role in both illnesses. Insulin activates key cancer processes including epithelial-mesenchymal transition (EMT), tissue inflammation, motility, and angiogenesis. There are key opportunities to impact and prevent hyperinsulinemia during breast cancer prevention, surgical assessment, and chemotherapy. Given the high prevalence of undiagnosed pre-diabetes and diabetes in the United States and worldwide, preoperative screening to identify such patients prior to surgical intervention is warranted. While it is not standard of care to test for insulin-resistance during the course of breast cancer screening and treatment, it is standard of care to screen and test high risk women for insulin-resistance as part of whole woman care. Given the important role insulin signaling plays in driving signaling pathways that promote aggressive cancer biology, more attention should be paid by cancer physicians to screening and treating insulin resistance. Several studies have reinforced a link between breast cancer risk and diabetes. Moreover, metformin significantly reduces breast cancer risk, compared to patients who are not using metformin and is independent of diabetes status. As metformin has an association with decreased breast cancer recurrence, as well as potentially improved survival, disparities in insulin resistance between black and white women with breast cancer is important to investigate. It is hypothesized that metformin decreases the development of resistance in breast cancer cells, thereby allowing current chemotherapy agents to work synergistically with metformin. Our objective is to elucidate whether or not metformin is efficacious in improving insulin resistance in black and white women with breast cancer and if racial disparities in breast cancer prognosis can be partially explained by differences in pre-diagnosis insulin resistance which are improved with metformin therapy.

Sex

Female

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

* Non-Hispanic white or black females
* Age \> = 18 years
* English speaking
* Newly diagnosed breast cancer
* BMI \> = 25 (must be overweight)
* Insulin-resistant (as determined by 2 hour 75 gm oral glucose tolerance test (OGTT)). Concentrations and trajectories of insulin and glucose at 0, 30, 60, and 120 min during an oral glucose tolerance test will undergo mathematical modeling. The numbers for defining insulin resistance have been established in the Woman's Laboratory and are interpreted by the pathologists.

Exclusion Criteria:

* Metastatic Disease
* Current diagnosis of Diabetes or diagnosed with diabetes (as determined by HbA1C\> 6.5)
* Having surgery prior to chemotherapy
* Medical conditions for which metformin is contraindicated (gastrointestinal and renal failure),
* Abnormal CBC (defined by a baseline platelet count of less than 130 and a baseline absolute neutrophil count of less than 1000). In addition, baseline hemoglobin of less than 10, if there is no evidence of a concurrent nutritional deficiency (like iron). \[Patients simply needing something like iron to correct the anemia will not be excluded\].