Challenges in Breast Pathology: New Twists on Old Problems (Special Section--Insights and Controversies in Breast Pathology) (Report) - Archives of Pathology & Laboratory Medicine

Challenges in Breast Pathology: New Twists on Old Problems (Special Section--Insights and Controversies in Breast Pathology) (Report)

By Archives of Pathology & Laboratory Medicine

  • Release Date - Published: 2009-06-01
  • Book Genre: Health & Fitness
  • Author: Archives of Pathology & Laboratory Medicine
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Challenges in Breast Pathology: New Twists on Old Problems (Special Section--Insights and Controversies in Breast Pathology) (Report) Archives of Pathology & Laboratory Medicine read online review & book description:

Predicting the potential for recurrence and metastases of carcinomas at the time of their initial presentation and diagnosis remains a significant challenge in management of patients with breast cancer. This is particularly critical for early-stage carcinomas, for which adjuvant chemotherapy is unnecessary in nearly 75% of cases. Gene expression profiling assays of breast carcinoma in some specific groups of patients have been used to predict outcome and avert unnecessary adjuvant chemotherapy. (1,2) These assays are being used to supplement traditional prognostic and predictive factors and may replace them in the future. It is crucial for pathologists to understand the nature of these assays and become familiar with the various assays available, the information provided by the assays, the differences between them, and their current limitations. Ein-Dor and Domany (3) have noted that while various groups using different gene sets have shown good predictive performance, overlap between the gene lists is rather small. Furthermore, they suggest that thousands of tumors have to be studied in order to obtain a 50% overlap between 2 sets of predictive genes. We are clearly in a discovery phase and everyone involved with these assays, including the pathologists who select the block of tissue for assessment at the request of the oncologist, should ask critical questions in order to ascertain procurement of a robust gene list for future analysis. Recent micro-array-based analyses of breast cancers have identified several clusters designated as luminal A (ER+, PR+, HER2/ neu-), luminal B (ER+, PR-, HER2/neu+), HER2+ (ER-, PR-, HER2/neu+), basal-like (ER-, PR-, HER2/ neu-; CK17+, CK14+, EGFR+, CK5/6+), and normal breastlike (ER- ,PR- , HER2/neu-) subtypes, where ER indicates estrogen receptor, PR indicates progesterone receptor, EGFR indicates epithelial growth factor receptor, and CK indicates cytokeratin. The basal-like category has attracted particular attention because it was suggested that this group is associated with a more aggressive behavior. While hormonal therapy and Herceptin are clearly of no value in management of basal-like carcinomas, there are many cancers that would fit the immunophenotype of this group (ER-, PR-, HER2-, but EGFR+ and CK5, CK14, and/or CK17+) that are either amongst the least aggressive of breast cancers or show a range of aggressiveness; among these are adenoid cystic carcinomas, squamous carcinomas, malignant myoepithelial lesions, and a few others. Since a vast majority of carcinomas evaluated for their gene expression profile have been of epithelial origin and have been infiltrating duct carcinomas, very few tumors of myoepithelial derivation or differentiation have been evaluated to clearly define their spectrum. When several hundred basal-like tumors are evaluated, undoubtedly a spectrum with a range of clinical behavior and variable degrees of aggressiveness will emerge just as we now recognize a variety of epithelial-derived lesions. Will we continue to have basal-like carcinomas or rather a range of myoepithelial derived/basal cancers? While we should be applying novel technologies to the assessment and classification of tumors, it is important to exercise caution in making conclusions based on the relatively small number of cases studied. The definitiveness with which some of the microarray-based findings is promoted may be premature, though the findings may be confirmed in larger studies. The point to keep in mind is that molecular-based classifications and gene expression-based predictive assays should not be treated as "The Emperor's New Clothes." In a more conventional arena, the introduction of novel approaches in sampling of tissues requires a constant and critical evaluation of our diagnostic criteria and adjustments to provide accurate diagnoses and recommendations for further therapy within the limitation of the samples available for analysis. Sentinel lymph node evaluation was int

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