Amplification Of TopoisomeraseⅡα And C-myc Gene In Breast Cancer And Its Correlation With Neoadjuvant Chemotherapy Response

[Background] Neoadjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer. Response to neoadjuvant chemotherapy is an important predictive marker of long-term outcomes. It is necessary to establish, prior to commencement of chemotherapy, predictors of clinical and pathological response. Such predictors may allow identification of patients who are most likely to benefit from such treatment. In addition to clinical and pathological parameters, it was reported that the amplification and overexpression of topoisomerase Ⅱα (TOPO Ⅱα) may be predictors of response to anthracyline-based neoadjuvant chemotherapy. Recent studies indicated that c-myc, a frequently amplified oncogene in breast cancer, may be associated with chemotherapy resistance. Here, a prospective study was conducted to ascertain whether these biological markers could be utilized as candidate predictors of response to neoadjuvant chemotherapy in breast cancer.[Patients and methods] The present study includes two parts. In the first part, fresh specimens from 82 untreated breast cancers were detected for the TOPO Ila and c-myc genes by Fluorescence in situ hybridization (FISH). The relationship between the two genes and clinical-pathological parameters were tested. In the second part, 41 cases of breast cancer with the primary tumor ≥3cm were prospectively designed to receive four cycle of EC regime (Epirubincin 80 mg/m~2, cyclophosphamide 600 mg/m~2) chemotherapy before surgery. The response to neoadjuvant chemotherapy was assessed clinically by the RECIST critia and pathologically by the Miller/Payne grading system. Touch imprint cytological samples from the pretreatment specimens were evaluated by FISH and immunocytochemical assay (ICA) for TOPO Ⅱα and c-myc. The role of these two genes in the prediction of clinical and pathological response was tested. The relationship between other parameters, including age, menopausal status, tumor size, lymph node status, stage, hormone receptor status, cerbB2 expression, and the response...