The estrogen receptor (ER) assay provides information which correlates with the proliferative potential, pathology and prognosis for patients with breast cancer. A review of our natural history data correlating ER and axillary node involvement at the time of mastectomy with prognosis allows the identification of a high risk subset of patients with early recurrence and poor survival. Patients with ER negative, stage II disease had a significantly higher recurrence rate, and poorer overall survival was observed in spite of systemic therapy instituted at relapse. Based on this data we initiated a pilot study of intensive adjuvant therapy for women with ER negative, stage II breast cancer. At a median follow-up of 19 months for 39 treated patients, both a disease free and overall survival advantage is apparent for treated patients. Morbidity was low, with no therapy related hospitalizations. We have demonstrated the feasibility of intensive therapy for this high risk group. For a definitive answer the patient resources of a cooperative group will be needed.