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Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
Authors:Silvina B Nadin  Mayra L Sottile  Maria M Montt-Guevara  Gisel V Gauna  Pedro Daguerre  Marcela Leuzzi  Francisco E Gago  Jorge Ibarra  F Darío Cuello-Carrión  Daniel R Ciocca  Laura M Vargas-Roig
Institution:1. Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
5. Institute of Medicine and Experimental Biology of Cuyo, C.C. 855 (5500), Mendoza, Argentina
2. Luis Lagomaggiore Hospital, Mendoza, Argentina
3. Medical School, National University of Cuyo, Mendoza, Argentina
4. Oncology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Research Council of Argentine, Mendoza, Argentina
Abstract:Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. Heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated, by immunohistochemistry, the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n?=?60) treated with doxorubicin (DOX)- or epirubicin (EPI)-based monochemotherapy. Serial biopsies were taken at days 1, 3, 7, and 21, and compared with prechemotherapy and surgical biopsies. After surgery, the patients received additional chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil. High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P?P?31 % of the cells) and cytoplasmic HSPA expressions (>11 % of the tumor cells) were associated with better DFS (P?=?0.0348 and P?=?0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy indicating the need to change the administered drugs after surgery for overcoming drug resistance.
Keywords:Breast cancer  Neoadjuvant chemotherapy  Anthracyclines  Heat shock proteins  Prognostic factors
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