Many lines of evidence support the view that BC is all too often a systemic disease and that micrometastases become enhanced after resection of the primary. Assuming that these two basic considerations do in fact apply, it can be argued that systemic treatment as the initial attack against operable BC has several advantages over the conventional postoperative adjuvant therapy: (a) Systemic treatment before operation may destroy clonogenic cells in the primary tumor which are responsible for the development of metastases; (b) primary tumor shrinkage following systemic therapy may serve as an early, simple, and inexpensive index of the overall chemosensitivity of the tumor; (c) systemic treatment as soon as the diagnosis is made may prevent the development of drug-resistant mutations, which are likely to form spontaneously early in the natural history of the disease; (d) preoperative chemotherapy may suppress the production of tumor-elaborated substances that protect the tumor from immune destruction by the host; (e) the average delay of about 1 month in the treatment of micrometastases in the postoperative adjuvant setting leads to at least a 30% increase of micrometastatic tumor burden, which can be prevented by preoperative treatment; (f) a number of other considerations suggest that the maximal chemosensitivity of each tumor exists at the earliest possible point in time, i.e., at the time of diagnosis; (g) after the initial postchemotherapy immunosuppression immunity recovers, in fact exceeding the pretreatment level, and if surgery is performed during this phase of heightened immunity chemotherapy is utilized as an immunostimulating agent; and finally (h) as more effective systemic agents are discovered, locoregional treatment with surgery and/or radiotherapy may become progressively more limited and it may ultimately be possible to dispense with these modalities. Experimental evidence scattered in the literature over the past three decades attests to the value of preoperative chemotherapy. Likewise, progressively greater numbers of uncontrolled studies have found preoperative chemotherapy most rewarding in miscellaneous sarcomas and in advanced tumors of the head and neck, kidney, and testes, as well as in a variety of other sites, including the breast.(ABSTRACT TRUNCATED AT 400 WORDS)