Neoadjuvant therapy of breast cancer: Current status

Primary systemic therapy is defined as the first systemic treatment a patient receives after cancer is diagnosed, and indicates that subsequent therapies are intended. It is also known as preoperative, induction, or neoadjuvant systemic therapy. Because of high tumor regression rates, primary systemic chemotherapy has become part of the standard of multidisciplinary care for patients with locally advanced and inflammatory breast cancer. An expert panel has reviewed all large randomized clinical trials of primary systemic chemotherapy versus adjuvant systemic therapy in operable breast cancer and concluded that both result in equivalent disease-free, local recurrence-free, and overall survival rates when compared head to head. However, the rate of successful breast-conserving surgery is statistically significantly increased in patients who receive primary chemotherapy; thus, primary systemic therapy is a reasonable alternative for patients with operable breast cancer who are deemed to be appropriate candidates for mastectomy but who desire breast-conserving surgery, or for those patients who desire less extensive breast-conserving surgery. The addition of taxanes or trastuzumab to primary systemic chemotherapy results in a significant increase in the overall and complete clinical response rates and in pathologic complete response (pCR) rates. A poor response to primary systemic chemotherapy is a predictor of poor prognosis and of a high risk of recurrence, irrespective of the type of surgery performed. In contrast, a pCR of the tumor or of cytologically documented axillary lymph node disease correlates strongly with both prolonged disease-free survival and overall survival, and occurs in 6-31% of patients, depending on the breast cancer subtype, the particular chemotherapy regimen used, and on the definition of what constitutes a pCR that is used by the particular group. Thus, pCR may be regarded as one major goal of primary systemic chemotherapy. Emerging data suggest that the achievement of pCR is associated with an excellent long-term outcome, regardless of the therapy regimen that results in pCR. If this association of pCR with outcome, regardless of the therapy regimen resulting in pCR, is confirmed, the application of newer gene- or protein-based technologies to predict at diagnosis which patients will achieve pCR in response to various biologic therapies and chemotherapies will have important clinical implications. In addition, the ability of pCR to predict an excellent long-term outcome may, with further study, become routinely applicable to the study of novel anticancer agents in the adjuvant setting, perhaps ultimately allowing us to avoid the need to perform large expensive trials with many years of follow-up.