Developments in chemotherapy of breast cancer

Breast carcinoma is moderately sensitive to multiple antitumor agents. Cytotoxic combination regimens developed in the 1970s were shown to produce higher response rates and longer durations of response and survival than single-agent therapy. These regimens became the standard of care for the management of metastatic, hormone-refractory breast carcinoma, and more recently, for primary breast carcinoma. Randomized trials also have demonstrated that anthracycline-containing combinations were more effective than combinations without anthracyclines. The development of several new cytotoxic agents and novel antitumor strategies prompted this review.

The author conducted a computerized literature search of MEDLINE and CANCERLIT and also reviewed the abstracts of major oncology meetings (ASCO, American Association for Cancer Research, ESMO, and San Antonio Breast Cancer Symposium) over the past 10 years.

Effective new cytotoxic drugs include the taxanes (paclitaxel and docetaxel), vinorelbine, gemcitabine, and capecitabine. The identification of specific molecular abnormalities (HER-2/neu or epidermal growth factor receptor [EGFR] overexpression) led to the development of targeted therapeutic intervention (monoclonal antibodies and tyrosine kinase inhibitors). Trastuzumab, a monoclonal antibody against the HER-2/neu oncoprotein, produced objective regression in 15-20% of patients with HER-2/neu-overexpressing breast carcinoma and improved the efficacy of paclitaxel. Other productive directions of therapeutic research include inhibition of intracellular signaling, interference with tumor angiogenesis, cell cycle regulation, and the development of vaccines.

Expanded understanding of the biology of breast carcinoma led to the development of rational therapeutic interventions, many of which are currently under active clinical development.