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Some of the breast cancer chemotherapy trials conducted during the past 25 years were reviewed. In general, most authors noted a significantly improved disease-free survival and overall survival in premenopausal patients but not in postmenopausal patients. Considering all patients, most authors found a significant increase in the disease-free survival but not in overall survival. In one study, the relapse rate increased with time. In the first three years, the relapse rate in the control group greatly exceeded that in the treatment group, but as the years went on, this trend reversed, and an increasing percentage of the treated group had relapse. More time is required to draw firm conclusions.
Some of the breast cancer chemotherapy trials conducted during the past 25 years were reviewed. In general, most authors noted a significantly improved disease-free survival and overall survival in premenopausal patients but not in postmenopausal patients. Considering all patients, most authors found a significant increase in the disease-free survival but not in overall survival. In one study, the relapse rate increased with time. In the first three years, the relapse rate in the control group greatly exceeded that in the treatment group, but as the years went on, this trend reversed, and an increasing percentage of the treated group had relapse. More time is required to draw firm conclusions.
Th pathobiology of breast cancer is complex: clinically "early" breast cancer may be tumor biologically "late" progressing rapidly toward death. Accordingly, it has been suggested that two different breast cancer populations (slow tumor growth and long survival-fast tumor growth and short survival) exist, which cannot be identified by pathohistological criteria. However, these "populations" are most likely either patients with localized disease and occult metastases (long survival) or with diagnosable regional and occult or overt systemic spread (short survival). Since even small tumors (0.1 to 0.3 cm in diameter) can spread systemically, in most patients breast cancer upon clinical diagnosis may be considered an inevitably lethal disease. Present treatment modalities can only improve the quality of life and delay death, even though the overall long-term survival rates of breast cancer are better or at least equal to those of other cancers. However, with other cancers (Table 2) it is decided within the first 5 years which patients are cured because the survival rates for 5, 10, 15, and 20 years are similar. In contrast, survival rates of patients with breast cancer steadily decline and there is no point in time when patients can feel really safe; this is indicative of a peculiar tumor pathobiology of this disease, the nature of which remains to be investigated. Progress in the fight against breast cancer is only possible by application of sensitive physical, reliable immunological, and specific biochemical methods for early diagnosis and development of efficient therapeutic modalities for inhibition of growth or complete eradication of metastasized cancer cells.
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.
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