BACKGROUND Neoadjuvant chemotherapy reduces tumor size prior to surgery in women with breast cancer. We assessed the ability of mammography and ultrasound to predict residual tumor size following neoadjuvant chemotherapy. METHODS In a retrospective review of consecutive breast cancer patients treated with neoadjuvant chemotherapy, residual tumor size estimated by diagnostic imaging was compared with residual tumor size determined by surgical pathology. RESULTS 192 patients with 196 primary breast cancers were studied. Of 104 tumors evaluated by both imaging modalities, ultrasound was able to size 91.3%, however, mammography was able to size only 51.9% of tumors (chi-square, p<.001). Ultrasound also was more accurate than mammography in estimating residual tumor size (62/104 [59.6%] versus 33/104 [31.7%], p < .001). There was little difference in the ability of mammography and ultrasound to predict pathologic complete response (ROC= 0.741 versus 0.784). CONCLUSIONS Breast ultrasound was more accurate than mammography in predicting residual tumor size following neoadjuvant chemotherapy. Likelihood of a complete pathological response was 80% when both imaging modalities demonstrated no residual disease.

Our study suggests a new role for FLX as an inducer of ER stress and autophagy, resulting in death of aggressive triple negative breast cancer SUM149PT.

Random periareolar fine needle aspiration (RPFNA) and ductal lavage (DL) are research techniques developed to (1) assess short-term breast cancer risk in asymptomatic women who are at increased risk for breast cancer and (2) track cytological response to risk reduction strategies. RPFNA and DL provide minimally invasive methods to repeatedly sample epithelial cells and research tools to investigate the biological origins of breast cancer in high-risk women. This review gives an overview of the strengths and limitations of both RPFNA and DL for risk assessment and breast cancer prevention in asymptomatic high-risk women.

Normal mammary gland homeostasis requires the coordinated regulation of protein signaling networks. However, we have little prospective information on whether activation of protein signaling occurs in premalignant mammary epithelial cells, as represented by cells with cytological atypia from women who are at high risk for breast cancer. This information is critical for understanding the role of deregulated signaling pathways in the initiation of breast cancer and for developing targeted prevention and/or treatment strategies for breast cancer in the future. In this pilot and feasibility study, we examined the expression of 52 phosphorylated, total, and cleaved proteins in 31 microdissected Random Periareolar Fine Needle Aspiration (RPFNA) samples by high-throughput Reverse Phase Protein Microarray. Unsupervised hierarchical clustering analysis indicated the presence of four clusters of proteins that represent the following signaling pathways: (1) receptor tyrosine kinase/Akt/mammalian target of rapamycin (RTK/Akt/mTOR), (2) RTK/Akt/extracellular signal-regulated kinase (RTK/Akt/ERK), (3) mitochondrial apoptosis, and (4) indeterminate. Clusters 1 through 3 comprised moderately to highly expressed proteins, while Cluster 4 comprised proteins that are lowly expressed in a majority of RPFNA samples. Our exploratory study showed that the interlinked components of mitochondrial apoptosis pathway are highly expressed in all mammary epithelial cells obtained from high-risk women. In particular, the expression levels of anti-apoptotic Bcl-xL and pro-apoptotic Bad are positively correlated in both non-atypical and atypical samples (unadjusted P < 0.0001), suggesting a delicate balance between the pro-apoptotic and anti-apoptotic regulation of cell proliferation during the early steps of mammary carcinogenesis. Our feasibility study suggests that the activation of key proteins along the RTK/Akt pathway may tip this balance to cell survival. Taken together, our results demonstrate the feasibility of mapping proteomic signaling networks in limited RPFNA samples obtained from high-risk women and the promise of developing rational drug targets or preventative strategies for breast cancer in future proteomic studies with a larger cohort of high-risk women.

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