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.

A B S T R A C T PurposeTo evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with confirmed triple receptor-negative breast cancer (TNBC). Patients and MethodsWe reviewed 1,711 patients with TNBC diagnosed between 1980 and 2009. Patients were categorized by tumor size and nodal status. Kaplan-Meier product limit method was used to calculate overall survival (OS) and relapse-free survival (RFS). A Sidak adjustment was used for multiple group comparisons. Cox proportional hazards models were fit to determine the association of tumor size and nodal status with survival outcomes after adjustment for other patient and disease characteristics. ResultsMedian age was 48 years (range, 21 to 87 years). At a median follow-up of 53 months (range, 0.7 to 317 months), there were 614 deaths and 747 recurrences. The 5-year OS was 80% for node-negative patients (N0), 65% for one to three positive lymph nodes (N1), 48% for four to nine positive lymph nodes (N2), and 44% for Ն 10 positive lymph nodes (N3; P Ͻ .0001). The 5-year RFS rates were 67% for N0, 52% for N1, 36% for N2, and 33% for N3 (P Ͻ .0001). Pairwise comparison by nodal status showed that when comparing N0 with node-positive disease, there was a significant difference in OS and RFS (P Ͻ .001 all comparisons). However, when comparing N1 with N2 and N3 disease regardless of tumor size, there were no significant differences in OS or RFS. ConclusionIn patients with TNBC, once there is evidence of lymph node metastasis, the prognosis may not be affected by the number of positive lymph nodes.

PURPOSE Brain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials. PATIENTS AND METHODS Electronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada). Results Of 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease-free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities. CONCLUSION We have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention.

Background It has been a matter of controversy whether there is an increased risk of lung cancer among asbestos‐exposed workers without radiographic asbestosis. A previous study of lung cancer risk among asbestos‐cement workers has been updated with an additional 12 years of follow‐up. Methods Subjects had received radiographic examination at 20 and 25 years from first exposure to asbestos. Radiographs were interpreted by a single National Institute of Safety and Health (NIOSH)‐certified B‐reader using the 1971 International Labor Office (ILO) Classification of the pneumoconioses as reference standard. Asbestosis was defined as an ILO coding of 1/0 or higher. Standardized Mortality Ratios (SMRs) were calculated using the general population of Ontario as reference. Results Among asbestos‐cement workers without radiographic asbestosis at 20 years latency the lung cancer SMR was 3.84 (2.24–6.14). Among workers without asbestosis when examined at 25 years latency the SMR was 3.69 (1.59–7.26). Conclusions Workers from an Ontario asbestos‐cement factory who did not have radiographic asbestosis at 20 or 25 years from first exposure to asbestos continued to have an increased risk of death from lung cancer during an additional 12 years of follow‐up. Am. J. Ind. Med. 53:1065–1069, 2010. © 2010 Wiley‐Liss, Inc.