The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53.
View Article and Find Full Text PDFBackground: This study sought to determine the likelihood of occult malignancy during risk-reducing mastectomy in high-penetrance pathogenic variant carriers to help refine axillary staging recommendations.
Methods: The authors performed a retrospective cohort study analyzing all female carriers of pathogenic variants in BRCA1/2, PALB2 or other genes who underwent prophylactic surgery at their institution between 2006 and 2021. Occult breast cancer was defined as the unanticipated presence of in situ or invasive malignancy on pathologic evaluation of prophylactic mastectomy specimens.
Purpose: Adjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved overall survival. Initiation of adjuvant chemotherapy within this time frame is therefore recommended by clinical practice guidelines, including the European Society for Medical Oncology. The objective of this study was to evaluate adherence to these clinical practice guidelines for patients with stage III colon cancer across the Rossy Cancer Network (RCN); a partnership of McGill University's Faculty of Medicine, McGill University Health Centre, Jewish General Hospital and St Mary's Hospital Center.
View Article and Find Full Text PDFThe nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.
View Article and Find Full Text PDFThe major obstacle in successfully treating triple-negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous preclinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphologic phenotype, which consists of polyploid giant cancer cells giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets.
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