Detection of predictive markers in breast carcinoma has undergone significant changes, the most important ones - at least in the context of Czech Republic - are related to the detection of HER2 - detection of both over-expression of oncoprotein HER-2/neu and amplification of the c-erbB-2 gene, respectively. In the Czech Republic, immunohistochemical testing is performed as a method of first choice, followed, if needed, by in situ hybridization. The update of the guidelines published in 2013 decreased the threshold for positive tumor cells from 30% to 10%, shifted the threshold for gene amplification (HER2/CEP17 ratio) from 2.2 to 2.0 and slightly changed criteria for classification of expression as 2+. These changes resulted in relatively significant increase of cases classified as "borderline" or "equivocal", requiring confirmation by in situ hybridization. In order to reduce the risk of false results, the cases diagnosed as positive in small (primary) laboratories, have to be confirmed in one of the large central laboratories. This confirmation of HER2 positivity is required before targeted therapy can be started. HER2 testing is recommended in core-cut biopsies virtually always; it is absolutely essential in patients undergoing neoadjuvant systemic therapy. In patients treated primarily by surgery can be the testing performed either in the core cut biopsy or in the final resection specimen. However, it should be kept in mind that the accuracy of some parameters in the core-cut biopsies may be limited, even in cases not influenced by the neoadjuvant chemotherapy (NACHT). The degree of concordance between results of molecular tests in the core-cut biopsy and resection specimen can achieve only 67 % and the precise concordance of histological typing reaches only 84 %, respectively; the concordance of HER2 expression, on the other hand, reaches more than 90%. In patients with positive HER2 result in core-cut biopsy, it is no longer required to repeat the testing in the resection specimen, whereas in case of HER2 negative core-cut biopsy, it is required to repeat the test from resection specimen to minimize the risk of false negative result. The probability of pathological complete response (pCR) varies in individual breast carcinoma subtypes - it reaches 27-51% in triple-negative and HER2+ cases, while in hormone-dependent tumors, namely in those with low proliferative activity, it is significantly lower. Even within the HER2+ carcinoma subgroup, the probability of pCR varies. HER2+ tumors co-expressing ER and PR have a lower rate of pCR than HER2+ carcinomas without co-expression of hormonal receptors. Carcinomas expressing high-molecular weight keratins (CK14, CK 5/6) with basal phenotype or tumors with mutations of HER2/AKT signal pathway (PI3K, PTEN) have also lower response to treatment and worse prognosis.
Keywords: breast carcinoma - HER2 - predictive diagnostics - molecular pathology - neoadjuvant treatment - pathologic response..