Biological markers as indicators of response to primary and adjuvant chemotherapy in breast cancer

Interest in translational studies on breast cancer is presently devoted to identify biological predictors of treatment response. In patients with oper able breast cancer, subjected to primary and adjuvant chemotherapy, we anal yzed the predictivity on objective clinical response and relapse-free survi val of biological markers related to different cellular aspects and functio ns. Tumour proliferative rate (evaluated as the H-3-thymidine-labelling ind ex, TLI), oestrogen and progesterone receptors (ER and PgR, evaluated by th e dextran-coated-charcoal method), nuclear DNA ploidy and the immunocytoche mical expression of p53, bcl-2 and bar proteins were determined before prim ary 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 th ose with ER+ (64% vs. 38%) or PgR(+) (53% vs. 37%) tumours. Such findings h eld true even within the sub-set of patients who received adjuvant postoper ative chemotherapy, i.e., those with node-positive (N+) or ER-/node-negativ e (N-) tumours, among whom also rapid proliferation or the presence of apop tosis-favouring markers (bcl-2(-) or bax(+), singly and in association) on surgical specimens identified a sub-set of women who benefited from systemi c 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, Pg R and, to a lesser extent, TLI and apoptosis-modulating markers. Int. J, Ca ncer (Pred. Oncol.) 84:580-586, 1999. (C) 1999 Wiley-Liss, Inc.