Primary chemotherapy in surgically resectable breast cancer

We have reviewed the current status of primary chemotherapy for resectable breast cancer in view of the possibility that it may improve on results of present adjuvant drug therapies. The observed kinetic acceleration of micrometastases following noncurative surgical excision in animal studies represents strong biologic evidence supporting primary chemotherapy. From a clinical perspective, primary chemotherapy has consistently reduced the frequency of mastectomy in women with tumors initially considered too large for breast-conserving surgery. From studies of various drug combinations, it appears that the incidence of pathologic complete remission usually remains less than 10 percent. Based on results from the Milan study, it appears that the degree of tumor response is a marker of treatment outcome, at least for the first five years. A higher complete-remission rate could be expected by combining doxorubicin with paclitaxel, as has already been observed in the treatment of clinically disseminated breast cancer. In spite of the logical and scientific rationale, the available data do not as yet provide sufficient evidence to indicate a clear superiority of primary chemotherapy over adjuvant chemotherapy. The real question to answer through prospective, randomized trials is not whether the shift from adjuvant to neoadjuvant chemotherapy will result in a superior outcome, but rather how to properly integrate effective primary and adjuvant drug regimens to maximize tumor cell kill. This strategy should be further tested in patients at high risk for occult axillary adenopathy and/or distant micrometastases (i.e., tumor size larger than 2 to 3 cm). However, a more-refined risk assessment approach (e.g., using tumor grade or proliferative index) will clearly be needed. The new treatment approach may also allow for a wider use of fine-needle aspiration biopsy to obtain the primary diagnosis of cancer, a more uniform adoption of breast-conserving surgery, and use of response to chemotherapy as a marker of treatment outcome.