Present State and Future Prospects: A Review of Cooperative Groups' Adjuvant and Neoadjuvant Trials in Breast Cancer

Abstract

In patients with operable breast cancer, adjuvant hormonal therapy and adjuvant chemotherapy result in significant and long-term reductions in the rates of disease recurrence and death. These reductions are evident in both patients with node-negative as well as in those with node-positive disease. However, several issues in the adjuvant treatment of breast cancer still remain unresolved. These issues were recently considered at the 2000 National Institutes of Health (NIH) Consensus Development Conference, which reviewed the current state of knowledge on adjuvant therapy and outlined strategies for future research. In the area of adjuvant hormonal therapy, tamoxifen is still the gold standard, and present evidence supports the use of tamoxifen for patients with estrogen receptor (ER)-positive tumors irrespective of age, menopausal status, nodal status, or tumor size. Optimal duration of tamoxifen therapy is about 5 years. Future research directions include evaluating the benefit of extending tamoxifen beyond 5 years, the contribution of ovarian ablation, and the role of hormonal manipulations involving selective ER modulators and aromatase inhibitors instead of or in addition to tamoxifen. In the area of adjuvant chemotherapy, polychemotherapy regimens have been consistently found to be superior to single agents, and anthracycline-containing regimens produce a small but statistically significant improvement in survival when compared with regimens not containing an anthracycline. High-dose adjuvant chemotherapy with stem cell support has not been proven superior to standard regimens. Neoadjuvant therapy offers the possibility of testing in vivo the sensitivity of individual tumors to particular cytotoxic regimens and, hence, of improving ultimate disease control, as well as reducing the extent of local therapy. The contribution and optimal integration of taxanes in the adjuvant setting are yet to be established but are the subject of intense research effort. Similarly, novel targeted therapies such as trastuzumab and bisphosphonates are currently being evaluated in adjuvant studies.