title: "Early" and "late" breast cancer: a unified concept for treatment.
abstract: Most women with "early" breast cancer have distant metastases by the time the primary growth comes to diagnosis. This observation is based upon the fact that these frequently appear despite successful removal of the primary growth, and given that they originate from the now no longer present tumour, the inescapable conclusion is that dissemination must have taken place prior to initial treatment. Failure to appreciate this rather obvious point results from shortcomings in available diagnostic technology, and inadequate usage of that which is available. Whether detected early or late, treatment of this disseminated cancer poses a common problem, and the various systemic methods are reviewed. Androgens, oestrogens, progestogens and single drug chemotherapy can, from time to time, produce useful results. By careful selection of patients with appropriate metastatic patterns, these methods may yield improved response rates up to 50% but, by and large, experience remains disappointing with across the board representative figures of perhaps 25% response being commonplace. Additionally, these methods are not without their side effects which can be distressing, and indeed on occasion life-threatening. Their short-comings have led to the development of cyclical combination chemotherapy as here reported. Cyclophosphamide, vincristine, 5-fluorouracil and methotrexate are administered for five consecutive days per month. The results obtained in 100 patients treated with this technique are compared with the authors' previous  experience with norethisterone acetate and hypophysectomy. Whether the results are considered in total or broken down into prognostic categories such as predominant metastatic pattern, disease-free interval, or age, combination chemotherapy has a clear advantage over other techniques. Whilst this experience does not constitute a randomised trial, it is considered that the results are so superior to previous treatment techniques as to render such a study unnecessary or even unethical. It is proposed that combination chemotherapy should constitute the first line of treatment for overt advanced breast cancer. It is further proposed that its role should be explored at an earlier stage in the treatment of breast cancer. Before this can take place however, treatment must be made less demanding and less toxic. Further research is underway with these aims in mind.
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use; D007016:Hypophysectomy; D008727:Methotrexate / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009640:Norethindrone / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D003520:Cyclophosphamide; D009640:Norethindrone; D005472:Fluorouracil; D008727:Methotrexate