title: Role of proliferation in HER2 status predicted response to doxorubicin.
abstract: The role of HER2 in predicting response to doxorubicin (DXR) therapy in breast cancer was evaluated in vivo in a series of breast carcinomas from 220 patients with tumors larger than 2.5 cm and treated with 3 cycles of DXR (75 mg/m(2)) as neoadjuvant chemotherapy. Patients with HER2-positive tumors were more frequently responsive to DXR treatment compared with HER2-negative patients (p = 0.05; Mantel-Haenszel Chi(2) = 0.009). Progesterone receptor (PgR) negativity, but not mutated p53, was also associated with response to DXR (p = 0.05; Mantel-Haenszel Chi(2) = 0.004). Further analysis of those correlations using breast carcinoma cell lines characterized for different biologic parameters revealed a trend between HER2 positivity/PgR negativity and greater DXR sensitivity, but the strongest direct correlation was found between the proliferation rate and sensitivity to DXR (r = 0.82, p = 0.00009). Neither p53 nor the DXR target molecule topoisomerase-II-alpha was significantly associated with in vitro sensitivity to DXR. Thus, whereas data showed that the major biologic parameter associated with in vitro response to DXR in breast cancer cells appears to be the tumor proliferation rate, HER2 expression together with PgR negativity may serve as the counterpart of the proliferation marker in predicting the in vivo response to DXR.
authors.affiliation: Department of Experimental Oncology, University of Milan, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Campiglio
authors.forename: Giulia
authors.initials: G
authors.lastname: Somenzi
authors.forename: Clelia
authors.initials: C
authors.lastname: Olgiati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Beretta
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ménard
mesh_terms: D000951:Antigens, Neoplasm; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D020360:Neoadjuvant Therapy; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II