title: Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.
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 < 0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P < 0.01) levels at postchemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in postchemotherapy biopsies, high nuclear (>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.
authors.affiliation: Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina, snadin@mendoza-conicet.gob.ar.
authors.forename: Silvina B
authors.initials: SB
authors.lastname: Nadin
authors.forename: Mayra L
authors.initials: ML
authors.lastname: Sottile
authors.forename: Maria M
authors.initials: MM
authors.lastname: Montt-Guevara
authors.forename: Gisel V
authors.initials: GV
authors.lastname: Gauna
authors.forename: Pedro
authors.initials: P
authors.lastname: Daguerre
authors.forename: Marcela
authors.initials: M
authors.lastname: Leuzzi
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Gago
authors.forename: Jorge
authors.initials: J
authors.lastname: Ibarra
authors.forename: F Darío
authors.initials: FD
authors.lastname: Cuello-Carrión
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ciocca
authors.forename: Laura M
authors.initials: LM
authors.lastname: Vargas-Roig
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D015251:Epirubicin; D004317:Doxorubicin