1,721,731 research outputs found
A bad tumor biomarker is as bad as a bad drug : The gap between genomics data and phenotype to predict response
No full textThe search for novel prognostic and predictive parameters in breast carcinoma is relentless. The new technological advances in gene expression profiling and in mutational analysis will hopefully prove to be clinically useful in informing the choice for the systemic therapy. For the time being, we are still relying in established immunohistochemical markers, namely estrogen and progesterone receptors, HER2 and Ki67. Advances in the harmonization of pre-analytical, analytical and interpretative variables may improve accuracy and reproducibility of the results
Integrating molecular profiling, histological type and other variables: defining the fingerprint of responsiveness to treatment.
No full textThe landscape of prognostication and prediction of responsiveness to systemic therapy for breast cancer patients has been recently enriched by the development of molecular assays, which enable to explore the whole universe of gene expression in the tumour cells and to unveil new prognostic and predictive markers. These molecular markers might well be used in combination with the established ones to address the many open questions that still pave the way to a truly personalized treatment. The actual clinical utility of the molecular assays is being tested in randomized clinical trials that require an unprecedented coordination of the activity of clinical investigators, pathologists and translational researchers worldwide
Characterization and clinical impact of residual disease after neoadjuvant chemotherapy
No full textOne of the most important lessons learned from trials of neoadjuvant chemotherapy (NACT) is that achievement of pathological complete response (pCR) is a powerful prognostic predictor of long-term outcome, with significantly better disease-free and overall survival for patients achieving pCR, as compared with patients having residual tumour after NACT. The pathologists' role in the neoadjuvant setting is: (i) to ensure an accurate assessment of pCR, and (ii) to evaluate burden and biological characteristics of residual tumour if pCR has not been achieved. A conversion of receptor status from the core biopsy to the post-NACT surgical specimen may cause uncertainty in the choice of the post-surgical systemic treatment for the patients. It is therefore imperative to ensure accuracy in the assessment of ER, PgR and HER2, and to double check any apparent conversion by re-staining the previous core biopsy and the residual tumour in the same run, thus minimizing the technical artifacts, and to use both immunohistochemical and in situ hybridization assays to evaluate HER2 status. It is essential that protocols for evaluation of tumour response and for assessment of prognostic/predictive parameters of residual disease after NACT be eventually harmonized
The current state of breast cancer classification
No full textBreast cancer is a highly heterogeneous disease due to its diverse morphological features, the variable clinical outcome and the response to different therapeutic options. It is therefore necessary to devise a clinically meaningful classification of the disease, which has to be scientifically sound, clinically useful and widely reproducible. The established histopathological classification has a limited clinical utility, due to insufficient prognostic and predictive power. More recent classification schemes, based on the immunohistochemical characterization of breast cancer for the assessment of hormone receptor status, HER2 gene over-expression or amplification and the proliferative fraction or on gene expression profiles, correlate much better with the clinical outcome and may be used to inform the choice of the systemic therapy
Histopathology of primary breast cancer 2005
No full textMajor efforts have been recently devoted to a better definition of intraductal proliferative lesions with atypia. The new WHO classification of tumors of the breast highlights the morphological features of flat epithelial atypia (DIN 1A) and atypical duct hyperplasia (DIN 1B). Flat epithelial atypia now encompasses lesions previously designated as clinging carcinoma (monomorphous type) and atypical columnar changes. Atypical ductal hyperplasia (ADH) is characterized by the same cytological changes as low-grade DCIS, involving a very small portion of the ductal tree. Minimal lymph node involvement includes true micrometastases (from 0.2 to 2 mm in size) and isolated tumor cells (ITC). ITC have been defined as individual tumor cells or small clusters of cells, not more than 0.2 mm in size, that do not typically show evidence of metastatic activity or penetration of vascular or lymphatic sinus walls. The biological and clinical implications of ITC remain to be elucidated
Pathological work up of the primary tumor: Getting the proper information out of it
No full textSummary: The primary tumour of patients with early breast cancer is the main source of information to assess the risk of disease recurrence and to inform the choice of the most appropriate systemic treatment. Accordingly, it is the main responsibility of the pathologists to ensure the patients and treating physicians that all the relevant information is derived from the primary tumour with the highest accuracy and reproducibility. The morphological changes of the tumour cells reflect the aggregate effects of changes occurring in hundreds of genes and may be a very faithful mirror of the biological and clinical behaviour of breast cancer. According to the 2009 St. Gallen Consensus, the systemic therapy of early breast cancer is mainly informed by the expression of hormone receptors and by the HER2 status, and the assessment of Ki67 has been included among the useful parameters to inform the choice of adding chemotherapy to endocrine therapies for patients with ER-positive and HER2-negative disease. A comprehensive approach that includes the accurate evaluation of the morphological features of the tumour, with special reference to the histological type and grade, and the assessment of the main prognostic and predictive parameters (ER, PgR, HER2 and Ki67) should offer to the patients and the treating physicians a robust background upon which the final therapeutic decisions can be safely taken
Be precise! The need to consider the mechanisms for CEP17 copy number changes in breast cancer
No full textA recent paper by Marchiò and colleagues indicated that true polysomy of chromosome 17 is rare and that coincident CEP 17 centromere amplification may account for its overestimation in FISH testing for HER2 amplification, with a treat/not treat decision as the final important readout. Here the importance of relating HER2 copy number to cell count rather than a ratio with CEP17 is emphasized. This is central to ensuring that all who may respond to potentially life-saving treatment with herceptin/lapatininib are not denied these drugs. Copyrigh
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