Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.

Concordance of quantitative hormone receptor measurements between primary and recurrent tumors is modest consistent with suboptimal reproducibility of measurement methods, particularly for IHC. Discordant cases have poor survival probably due to inappropriate use of targeted therapies. However, biological change in clinical phenotype cannot be completely excluded.

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.

The detection of CTCs prior to and during therapy is an independent and strong prognostic marker, and it is predictive of poor treatment outcome. A major challenge is that different technologies are available for isolation and characterization of CTCs in peripheral blood (PB). We compare the CellSearch system and AdnaTest BreastCancer Select/Detect, to evaluate the extent that these assays differ in their ability to detect CTCs in the PB of MBC patients. CTCs in 7.5 ml of PB were isolated and enumerated using the CellSearch, before new treatment. Two cutoff values of 2 and 5 CTCs/7.5 ml were used. AdnaTest requires 5 ml of PB to detect gene transcripts of tumor markers (GA733-2, MUC-1, and HER2) by RT-PCR. AdnaTest was scored positive if 1 of the transcript PCR products for the 3 markers were detected at a concentration 0.15 ng/ll. A total of 55 MBC patients were enrolled. 26 (47%) patients were positive for CTCs by the CellSearch (2 cutoff), while 20 (36%) were positive (5 cutoff). AdnaTest was positive in 29 (53%) with the individual markers being positive in 18% (GA733-2), 44% (MUC-1), and 35% (HER2). Overall positive agreement was 73% for CTC2 and 69% for CTC5. These preliminary data suggest that the AdnaTest has equivalent sensitivity to that of the CellSearch system in detecting 2 or more CTCs. While there is concordance between these 2 methods, the AdnaTest complements the CellSearch system by improving the overall CTC detection rate and permitting the assessment of genomic markers in CTCs.

Risk, II.