To determine whether preoperative chemotherapy sufficiently downstages disease in patients with locally advanced breast cancer to allow breast-conservation surgery, the clinical, mammographic, and histologic responses were analyzed after three cycles of preoperative vincristine, doxorubicin, cyclophosphamide, and prednisone that were administered to 143 patients with 1988 American Joint Committee on Cancer Stage IIB (17%), IIIA (36%), or IIIB (41%) disease or positive supraclavicular lymph nodes (6%) who had a complete (16%) or partial (84%) clinical response and underwent total mastectomy and axillary node dissection. Thirty-three (23%) were potential breast-conservation candidates based on criteria of complete resolution of skin edema, residual tumor size less than 5 cm, and absence of known tumor multicentricity or extensive intramammary lymphatic invasion. Of these 33, the initial tumor size decreased from a median of 5 cm to less than 1 cm, with 42% having no residual tumor in the mastectomy specimen and 45% having negative nodes. No tumor was found in any other quadrant of the breast, and no patient had a recurrence in the chest wall. After a median follow-up of 34 months, only three patients had distant metastases; two of these died of disease.