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Background Recent observational studies have shown that metformin use in diabetics decreases both cancer incidence and mortality. Metformin use is also independently predictive of pathologic complete response. We explored the association between metformin use and survival outcomes in patients with triple receptor-negative breast cancer (TNBC) receiving adjuvant chemotherapy. Methods The Breast Cancer Management System database of The University of Texas M.D. Anderson Cancer Center identified 1448 women who received adjuvant chemotherapy for TNBC between 1995 and 2007. Patients were categorized by diabetes status and metformin use. Kaplan-Meier product limit method was used to calculate distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS). Cox proportional hazards models were fit to determine the association between metformin use and survival outcomes. Results Our study cohort consisted of 63 diabetic patients taking metformin, 67 diabetic patients not taking metformin, and 1318 non-diabetic patients. Patients in the diabetic groups tended to be older (P=0.005); more diabetic patients were postmenopausal (P=0.0007), black (P=0.0001), and obese (P < 0.0001). At a median follow-up of 62 months, there were no significant differences in 5-year DMFS (P=0.23), RFS (P=0.38), and OS (P=0.58) between the three groups. Compared to the metformin group, patients who did not take metformin (Hazard ratio [HR]=1.63; 95% CI:0.87 to 3.06; P=0.13) and nondiabetics (HR=1.62; 95% CI:0.97 to 2.71; P=0.06) tended to have a higher risk of distant metastases. Conclusion Our findings suggest that metformin use during adjuvant chemotherapy does not significantly impact survival outcomes in diabetic patients with TNBC.

A B S T R A C T PurposeTo compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. Patients and MethodsA total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. ResultsFifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P Ͻ .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] ϭ 3.16; 95% CI, 1.55 to 6.42; P ϭ .002), estrogen receptor (ER) negativity (OR ϭ 1.96; 95% CI:1.05 to 3.65; P ϭ .03) and concurrent trastuzumab use (OR ϭ 4.18; 95% CI, 2.04 to 8.57; P Ͻ .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P ϭ .001) and OS (P ϭ .01) rates than patients who did not. ConclusionBRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.

Triple-negative breast cancer (TNBC) refers to a heterogeneous group of tumors that do not express the estrogen/progesterone-receptor (ER/PR), and human epidermal growth factor receptor-2 (HER2). TNBC is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapy regimens. There have been significant improvements in the outcome of other subtypes of breast cancer, including ER-positive/HER2 overexpressed tumors, attributed to the addition of targeted therapy, including hormonal agents and trastuzumab. However, no specific targeted agents are currently available for the treatment of TNBC. This review aims to collate and describe the most recent data on targeted therapies that have demonstrated efficacy in the management of metastatic TNBC. Targeted agents that have been investigated in the treatment of metastatic TNBC include inhibitors of poly(ADP-ribose) polymerase, angiogenesis, mammalian target of rapamycin, epidermal growth factor receptor, HDAC, Jak2, and Src. Several of these agents have shown considerable promise.