TY - JOUR
T1 - Biological markers as indicators of response to primary and adjuvant chemotherapy in breast cancer
AU - Daidone, Maria Grazia
AU - Veneroni, Silvia
AU - Benini, Elvira
AU - Tomasic, Gorana
AU - Coradini, Danila
AU - Mastore, Marinella
AU - Brambilla, Cristina
AU - Ferrari, Laura
AU - Silvestrini, Rosella
PY - 1999
Y1 - 1999
N2 - 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 3H-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 postoperative 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.
AB - 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 3H-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 postoperative 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.
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U2 - 10.1002/(SICI)1097-0215(19991222)84:6<580::AID-IJC7>3.0.CO;2-W
DO - 10.1002/(SICI)1097-0215(19991222)84:6<580::AID-IJC7>3.0.CO;2-W
M3 - Article
C2 - 10567902
AN - SCOPUS:0032763581
VL - 84
SP - 580
EP - 586
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 6
ER -