Adjuvant chemotherapy of breast cancer: hope--reality--hazard?

According to a NIH Consensus-Development Statement, adjuvant polychemotherapy following mastectomy is considered beneficial to premenopausal patients with positive axillary nodes. Nevertheless, the role of adjuvant chemotherapy in relation to menopausal status, axillary lymph node status, estrogen receptor status, choice and dose of agents, and long-term survival is not defined. Based on experimental background information and theoretical deductions, the clinical results have fallen short of expectations. The data of Bonadonna's CMF study reveal that the overall 5-year survival is increased by 4%; premenopausal patients benefit by 12% whereas treated postmenopausal patients have a 5% less chance of survival. Only those patients benefit who can tolerate a "full or nearly full dose"; these are only 17%. At this time it is not clear whether the small survival differences from adjuvant chemotherapy represent a real step forward in the fight against breast cancer. In the majority of patients (75 to 85%), at the time of adjuvant chemotherapy, systemically disseminated cancer cells are at mitotic rest or their proliferation is minimal. At this stage, adjuvant chemotherapy has no or little effect. Therefore, only a small proportion of patients (15 to 25%) has subclinical systemic cancer growth at the time of primary therapy or thereafter; only these patients have a chance to respond to chemotherapy. In view of this tumor kinetic problem and the hazards of chemotherapy, it seems advantageous (a) to focus on definition of patient subgroups at high risk for early recurrence post primary therapy to serve as participants in trials of adjuvant chemotherapy and/or (b) to concentrate on early diagnosis of recurrent disease for immediate institution of endocrine- and/or polychemotherapy.