U.S. Experience in Neoadjuvant Therapy of Operable Breast Cancer

Abstract

Primary systemic chemotherapy has become an integral part of treatment for patients with locally advanced or borderline inoperable patients. The objective of this manuscript was to review the US experience with preoperative chemotherapy in patients with operable breast cancer. National Surgical Adjuvant Breast and Bowel Project B-18 protocol was designed to determine whether preoperative doxorubicin cyclophosphamide would permit more lumpectomies to be performed and decrease the incidence of positive lymph nodes in women with primary breast cancer. This study established that preoperative chemotherapy reduced the size of most breast tumors and increased the lumpectomy rate after preoperative chemotherapy. The National Surgical Adjuvant Breast and Bowel Project B-27 protocol was designed to determine the effect of adding docetaxel after four cycles of doxorubicin cyclophosphamide on clinical and pathological response and on disease-free and overall survival. The addition significantly increased the clinical and pathological response rates, but the initial data showed no significant impact on event-free or survival rates, although it significantly reduced recurrence rates. M.D. Anderson Cancer Center (MDACC) ID94-002 study was designed to compare the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin (adriamycin), and cyclophosphamide; the data showed that single-agent paclitaxel as a neoadjuvant therapy had significant antitumor activity and its clinical efficacy was comparable to fluorouracil, doxorubicin (adriamycin), and cyclophosphamide. MDACC ID98-240 study was designed to determine if a change in the schedule of paclitaxel from once every 3 weeks to weekly administration would impact on the pathological complete response rates; the data demonstrated that the therapeutic index of paclitaxel was significantly enhanced when the drug was given on a weekly schedule. The MDACC ID99-146 trial’s primary objective was to compare the pathological complete response rates following chemotherapy alone to the same chemotherapy with trastuzumab in the neoadjuvant setting; data from this study illustrated that the addition of trastuzumab to chemotherapy significantly increased pathological complete response.