Neoadjuvant chemotherapy for operable breast cancer: is this the future?

The idea of using preoperative or neoadjuvant chemotherapy in patients with operable breast cancer originated from experimental and clinical observations as well as theoretical hypotheses on tumor cell growth and dissemination. Initially, nonrandomized studies demonstrated considerable rates of clinical tumor response, low rates of pathologic complete response (pCR), and increased rates of breast-conserving procedures. However, nonrandomized studies could not address the relative efficacy of neoadjuvant versus adjuvant chemotherapy on disease-free and overall survival. Similarly, earlier randomized trials were not designed as straightforward comparisons of neoadjuvant versus adjuvant chemotherapy and therefore could not adequately address the relative efficacy of neoadjuvant versus adjuvant chemotherapy on outcome. These answers were eventually provided by larger randomized trials that directly compared neoadjuvant with adjuvant chemotherapy, which are reviewed in more detail in this article. Potential advantages and disadvantages of the neoadjuvant approach and surgical considerations in the breast and axilla after neoadjuvant chemotherapy are also discussed. Finally, several recently reported trials of neoadjuvant therapy incorporating newer agents such as taxanes in sequence with anthracycline-containing regimens have shown further increases in pCR rates. Although outcome data are not available yet from these studies, it is hoped that the observed increase in pCR rates will be associated with improved outcome. If the previously observed significant correlation between the achievement of pCR and improved outcome continues to be demonstrated with these newer regimens, it will substantially strengthen the rationale for using neoadjuvant rather that adjuvant chemotherapy in the clinical setting as well as in future research studies.