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Role of proliferation in HER2 status predicted response to doxorubicin
Author(s) -
Campiglio Manuela,
Somenzi Giulia,
Olgiati Clelia,
Beretta Giovanni,
Balsari Andrea,
Zaffaroni Nadia,
Valagussa Pinuccia,
Ménard Sylvie
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11113
Subject(s) - in vivo , doxorubicin , breast cancer , negativity effect , medicine , chemotherapy , cancer research , proliferation marker , oncology , in vitro , cancer , cell growth , biology , pathology , immunohistochemistry , psychology , social psychology , biochemistry , genetics , microbiology and biotechnology
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 X 2 = 0.009). Progesterone receptor (PgR) negativity, but not mutated p53, was also associated with response to DXR ( p = 0.05; Mantel‐Haenszel X 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‐α 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. © 2003 Wiley‐Liss, Inc.