Biologic markers as predictors of clinical outcome from systemic therapy for primary operable breast cancer

Purpose: To determine whether pretreatment clinical features and molecular markers, together with changes in these factors, can predict treatment resp onse and survival in patients with primary operable breast cancer who recei ve neoadjuvant therapy. Patients and Methods: Mitoxantrone, methotrexate (with or without mitomycin ), and tamoxifen chemoendocrine therapy was administered to 158 patients be fore surgery. Clinical response was assessed after four cycles of treatment . Fine-needle aspiration cytology for estrogen receptor (ER), progesterone receptor (PSR), c-erbB-2, p53, bcl-2, Ki67, S-phase fraction (SPF), and plo idy were performed pretreatment and repeated on day 10 or day 21 after the first cycle of treatment. Results: Good clinical response (GCR, defined as complete response or minim al residual disease) wets achieved in 31% of patients (49 of 158). Tumor si ze, nodal disease, response, ER, pgR, c-erbB-2, p53, bcl-2, Ki67, SPF, and ploidy were analyzed as predictors of survival. By univariate analysis, nod e-positive disease (P = .05), lack of ER (P < .05) and PgR (P < .05), and f ailure to attain GCR (P = .008) were associated with a significantly increa sed risk of relapse. A significantly increased risk of death was associated with node-positive disease (P = .02), lack of ER expression (P = .04), and failure to attain GCR, By multivariate analysis, GCR was an independent pr edictor for survival (P = .05). ER expression (P = .03), absence of c-erbB- 2 (P = .03), and a decrease in Ki67 on day 10 or day 21 of the first cycle (P < .05) significantly predicted for subsequent GCR. Conclusion: Molecular markers may be used to predict the likelihood of achi eving GCR, which seems to be a valid surrogate marker for survival. (C) 199 9 by American Society of Clinical Oncology.