EFFECT OF PREOPERATIVE CHEMOTHERAPY ON THE OUTCOME OF WOMEN WITH OPERABLE BREAST-CANCER

Purpose: To determine, in women with primary operable breast cancer, i f preoperative doxorubicin (Adriamycin) and cyclophasphamide (Cytoxan: AC) therapy yields a better outcome than postoperative AC therapy if a relationship exists between outcome and tumor response to preoperati ve chemotherapy, and if such therapy results in the performance of mor e lumpectomies. Patients and Methods: Women (1,523) enrolled onto Nati onal Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were rand omly assigned to preoperative or postoperative AC therapy. Clinical tu mor response to preoperative therapy was graded as complete (cCR), par tial (cPR), or no response (cNR). Tumors with a cCR were further categ orized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DD FS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor r esponse. Results: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in eith er group. More patients treated preoperatively than postoperatively un derwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively) . Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). O utcome was better in women whose tumors showed a pCR than in those wit h a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9% , 68.1%, and 63.9%, respectively; P < .0001), even when baseline progn ostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breas t tumor response as a variable, discriminated outcome among patients t o about the same degree as the postoperative model. Conclusion: Preope rative chemotherapy is as effective as postoperative chemotherapy, per mits more lumpectomies, is appropriate for the treatment of, certain p atients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of ch emotherapy on micrometastases; however, knowledge of such a response p rovided little prognostic information beyond that which resulted from postoperative therapy. J Clin Oncol 16: 2672-2685. (C) 1998 by America n Society of Clinical Oncology.