The use of adjuvant chemotherapy in stage II breast cancer in the last 25 years--a brief review

This review summarizes more than 25 years of experience with the use of systemic chemotherapy in the adjuvant setting in patients suffering from stage II breast cancer. The use of the CMF combination in the early 70's marks the onset of the modern era of this modality. Adjuvant chemotherapy must be given at optimal doses and schedule, usually for a period lasting about six months, beginning shortly after the resection of the primary tumor. The incorporation of the anthracyclines, adriamycin and epirubicin represent an important milestone in the developmental history of the adjuvant chemotherapy of breast cancer. The sequential administration of adriamycin followed by CMF in patients with 4 or more involved axillary lymph nodes deserves particular emphasis. Meta-analysis of multiple clinical trials including several tens of thousands of patients with stage II breast cancer indicate that adjuvant chemotherapy results in a significant increase in both recurrence-free and overall survival as compared to locoregional treatment only. This holds true with long-term follow-up of 20 years and more as illustrated by the CMF experience, showing about a 35% decrease in the relative risk of recurrence. Efforts in recent years are investigating the role of newer cytotoxic agents such as the taxanes in the adjuvant setting. Furthermore, clinical trials are now ongoing with the use of the monoclonal antibody herceptin in patients with stage II breast cancer whose tumor over-expresses the oncogene Her2neu. The administration of adjuvant chemotherapy has the potential for undesirable side effects such as an increased risk of osteoporosis and ischemic heart disease in younger patients in whom amenorrhea develops, or cardiotoxicity from anthracyclines. Most clinical trials to date have not shown an increase in the occurrence of second primary tumors among patients receiving adjuvant chemotherapy for breast cancer. Adjuvant chemotherapy has become an integral part of the treatment of stage II breast cancer.