Improved Rate of Negative Margins for Inflammatory Breast Cancer Using Intraoperative Frozen Section Analysis.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer with a poor survival rate. Modified radical mastectomy (MRM) with negative pathologic margins is critical for improved survival. We aim to study the potential benefit of intraoperative frozen section analysis (FSA) to improve disease-free margins. METHODS: This prospective, monocentric study included 19 patients who underwent MRM for IBC. For each patient, a 2 mm continuous skin edge was sent for FSA to guide further resection. The rate of tumor-free margins and the concurrence between the FSA and permanent pathological results were analyzed. RESULTS: Overall, 15 of the 19 patients achieved negative margins, including four patients who would have had positive margins without FSA. The odds ratio of achieving a negative final margin with FSA was infinity (p = 0.031), and there was a strong agreement between the FSA and permanent pathological results (Kappa-0.83; p < 0.0001). CONCLUSIONS: The FSA technique decreased the number of positive margins in IBC patients undergoing MRM, thereby potentially reducing the need for re-operation, allowing immediate wound closure, and preventing delays in the administration of adjuvant radiation therapy. More extensive trials are warranted to establish the use of intraoperative FSA in IBC treatment.

Improving the quality of life in breast cancer survivors at risk for lymphedema.

BACKGROUND: Certain treatments increase lymphedema risk in breast cancer survivors. The purpose of this study was to determine whether quality of life improved with preoperative teaching by a lymphedema expert. METHODS: Preoperative breast cancer patients were prospectively randomized into intervention group 1 or control group 2. Group 1 had a discussion with the lymphedema expert and at 6 months, in addition to the preoperative surgical discussion and literature given to all. Arm measurements and quality of life evaluation with Functional Assessment of Cancer Therapy-Breast Cancer were completed preoperatively and at intervals for up to 3 years. Lymphedema was verified with a 10% increase in volume or circumference. Univariate and multivariate analysis were performed on data. RESULTS: There were 119 evaluable patients with no differences between groups 1 and 2. The rate of acute lymphedema was 51.5% (33 of 64) for group 1 and 47.2% (26 of 55) for group 2. Chronic lymphedema presented in 13 patients (9.3% group 1 and 12.7% group 2). Lymphedema was significantly associated with number of lymph nodes resected (P < .001). Significant findings in the Functional Assessment of Cancer Therapy-Breast Cancer were at 6 months for all and after diagnosis in lymphedema positive patients. CONCLUSION: Structured lymphedema teaching can help to improve quality of life in lymphedema patients.

Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells.

Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.

Strategic Endothelial Cell Tube Formation Assay: Comparing Extracellular Matrix and Growth Factor Reduced Extracellular Matrix.

Malignant tumors require a blood supply in order to survive and spread. These tumors obtain their needed blood from the patient's blood stream by hijacking the process of angiogenesis, in which new blood vessels are formed from existing blood vessels. The CXCR2 (chemokine (C-X-C motif) receptor 2) receptor is a transmembrane G-protein-linked molecule found in many cells that is closely associated with angiogenesis(1). Specific blockade of the CXCR2 receptor inhibits angiogenesis, as measured by several assays such as the endothelial tube formation assay. The tube formation assay is useful for studying angiogenesis because it is an excellent method of studying the effects that any given compound or environmental condition may have on angiogenesis. It is a simple and quick in vitro assay that generates quantifiable data and requires relatively few components. Unlike in vivo assays, it does not require animals and can be carried out in less than two days. This protocol describes a variation of the extracellular matrix supporting endothelial tube formation assay, which tests the CXCR2 receptor.

Histopathologic evidence of tumor regression in the axillary lymph nodes of patients treated with preoperative chemotherapy correlates with breast cancer outcome.

BACKGROUND: The benefits of primary tumor downstaging and assessment of chemoresponsiveness have resulted in expanded applications for induction chemotherapy. However, the pathologic evaluation and prognostic significance of response in preoperatively treated lymph nodes have not been defined. METHODS: The axillary lymph nodes of 71 patients with locally advanced breast cancer treated with induction chemotherapy were evaluated for histological evidence of tumor regression as defined by the presence of nodal fibrosis, mucin pools, or aggregates of foamy histiocytes. RESULTS: Complete pathologic response in the breast and axilla occurred in 10 patients (14%); 19 (26.8%) had evidence of tumor regression in 1 or more lymph nodes. Patients without nodal metastases and no evidence of tumor regression had the best outcome (median disease-free survival, 31.5 months; relapse rate, 27%). Patients with residual nodal metastases and no evidence of treatment effect had the worst outcome (median disease-free survival, 19.8 months; relapse rate, 55%). The median disease-free survival was 22.1 months, and the relapse rate was 32% for patients with histopathologic evidence of tumor regression in the axillary lymph nodes. CONCLUSIONS: Detection of treatment effect in axillary lymph nodes after induction chemotherapy identifies a subset of patients with an outcome intermediate between that of completely node-negative and node-positive patients. The axillary lymph nodes of patients receiving preoperative chemotherapy should be routinely analyzed for the presence of these features.