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Biological markers as indicators of response to primary and adjuvant chemotherapy in breast cancer
Author(s) -
Daidone Maria Grazia,
Veneroni Silvia,
Benini Elvira,
Tomasic Gorana,
Coradini Danila,
Mastore Marinella,
Brambilla Cristina,
Ferrari Laura,
Silvestrini Rosella
Publication year - 1999
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/(sici)1097-0215(19991222)84:6<580::aid-ijc7>3.0.co;2-w
Subject(s) - oncology , breast cancer , medicine , adjuvant chemotherapy , chemotherapy , adjuvant , cancer , mammary gland
Interest in translational studies on breast cancer is presently devoted to identify biological predictors of treatment response. In patients with operable breast cancer, subjected to primary and adjuvant chemotherapy, we analyzed the predictivity on objective clinical response and relapse‐free survival of biological markers related to different cellular aspects and functions. Tumour proliferative rate (evaluated as the 3 H‐thymidine‐labelling index, TLI), oestrogen and progesterone receptors (ER and PgR, evaluated by the dextran‐coated‐charcoal method), nuclear DNA ploidy and the immunocytochemical expression of p53, bcl‐2 and bax proteins were determined before primary treatment, at the time of diagnosis, and after primary chemotherapy, at surgery. Objective clinical response was significantly related only to pre‐treatment p53 expression or PgR status, with a higher rate for tumours not expressing than for those expressing p53 (94% vs. 72%), as well as for PgR‐negative (PgR − ) than for PgR‐positive (PgR + ) tumours (86% vs. 68%). In the overall series, 8‐year clinical outcome was significantly related only to post‐treatment steroid receptors. In particular, higher 8‐year relapse‐free survival rate was observed for patients with ER − or PgR − than for those with ER + (64% vs. 38%) or PgR + (53% vs. 37%) tumours. Such findings held true even within the sub‐set of patients who received adjuvant post‐operative chemotherapy, i.e., those with node‐positive (N + ) or ER − /node‐negative (N − ) tumours, among whom also rapid proliferation or the presence of apoptosis‐favouring markers (bcl‐2 − or bax + , singly and in association) on surgical specimens identified a sub‐set of women who benefited from systemic treatment. The different biological markers were variously indicative of clinical outcome, with a predictivity on tumour shrinkage for p53 and PgR, detected before primary chemotherapy, and on long‐term follow‐up for ER, PgR and, to a lesser extent, TLI and apoptosis‐modulating markers. Int. J. Cancer (Pred. Oncol.) 84:580–586, 1999. © 1999 Wiley‐Liss, Inc.