Preoperative (neoadjuvant) chemotherapy in patients with breast cancer.

The concept of using preoperative chemotherapy in patients with operable breast cancer originated from experimental and clinical observations, as well as from theoretical hypotheses on tumor cell growth and dissemination. Results from nonrandomized studies with different chemotherapeutic agents or combination regimens given preoperatively demonstrated substantial clinical response rates but low pathologic tumor response rates. In addition, several such studies were able to show that-by reducing primary breast tumor size-preoperative chemotherapy can lead to an increase in the rate of breast-preserving procedures. Although nonrandomized studies provided useful clinical information about the effect of preoperative chemotherapy on primary breast tumors and on axillary nodes involved with tumor, they could not address the relative efficacy of preoperative versus postoperative (adjuvant) chemotherapy on disease-free survival (DFS) and overall survival (OS). As a result, several randomized trials were implemented to address the above questions. Some of the earlier trials, however, were not designed as straightforward comparisons of preoperative versus postoperative chemotherapy and, thus, did not provide meaningful answers to the fundamental question of whether DFS and OS can be prolonged by the administration of chemotherapy before surgery rather than after. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial was the largest randomized trial that aimed to compare preoperative to postoperative chemotherapy in operable breast cancer. Results from this trial on the effect of preoperative chemotherapy on local-regional disease and outcome are presented. The potential advantages and disadvantages of each approach, as well as surgical considerations and current and future directions in the use of preoperative chemotherapy, are also discussed.