Reviewers: John Han-Chih Chang, MD
Source: Journal of Clinical Oncology Jul 1997; Volume 15: pages 2483 - 93
This article details the preliminary data from the National Surgical Adjuvant Breast and Bowel Project trial B-18. This study was designed to evaluate the efficacy of neoadjuvant or (preoperative) chemotherapy in affording breast cancer patients a recurrence prevention benefit and/or an overall survival advantage. Another major aim of the trial was to evaluate whether such neoadjuvant therapy could also reduce the size of the primary tumor so that there would be an increased likelihood that breast conservation treatment (with lumpectomy and definitive radiation therapy) could be performed as opposed to mastectomy.
The study was initiated in 1988, and over 1500 patients were randomized to receive either neoadjuvant chemotherapy (AC) doxorubicin (adriamycin) and cyclophosphamide (cytoxan) for four cycles prior to surgery or surgery followed by postoperative AC for four cycles. Radiation therapy in all lumpectomy patients followed the surgery in the neoadjuvant group and was after the AC in the postoperative group. Patients were eligible with any size tumors but ineligible if the tumors involved the chest wall or skin surface. Eligible patients either had mobile axillary lymph node metastases or none. All patients over the age of 50 received tamoxifen therapy for five years after the chemotherapy was completed.
The article focused on the over 700 patients who were randomized to receive adjuvant chemotherapy. The data on disease free survival (survival free of recurrent disease) and overall survival was not "mature" enough to make any significant conclusions. There will be an article in the future about that information when longer follow up is recorded. The results revealed that the neoadjuvant therapy caused an objective response in 80% of the primary tumor and lymph nodes. The response was defined as a greater than or equal to 50% reduction in the size of the palpable cancer in two dimensions after two to four cycles of AC. 245 patients had the tumor clinically "disappear" after neoadjuvant therapy, but on microscopic evaluation only 26% of those patients had no cancer left. The difference in the ability to perform lumpectomy was significant but small -- 67% patients had lumpectomies with neoadjuvant treatment versus 60% in those treated with postoperative AC. The difference was the greatest in those with tumors greater than five centimeters -- 22% in the neoadjuvant group versus 8% in the postoperative group.
What this trial has demonstrated is that it is possible in some circumstances to use neoadjuvant chemotherapy to decrease the size of primary breast tumors not considered to be candidates for breast conservation therapy with lumpectomy and definitive radiation therapy. Whether this treatment will lend a survival or local control advantage to these patients is yet to be worked out. Neoadjuvant chemotherapy would not be indicated in cases where lumpectomy is already a viable option or the patients desires mastectomy. In that circumstance, postoperative chemotherapy would only be used in cases of high risk features discovered at the time of surgery.
Despite this study, recommendations to utilize neoadjuvant chemotherapy remain guarded because of the significant yet very small (7%) benefit in increased rates of breast preservation. It is often more beneficial to proceed with the local therapy of surgery and/or radiation prior to initiating systemic chemotherapy in spite of its potential local benefit.