Combined sequential approach in locally advanced breast cancer

Background. The interaction between primary and adjuvant chemotherapy is a crucial point in the treatment of locally advanced breast cancer. Objective. To evaluate the therapeutic efficacy of a sequential treatment w ith primary anthracyclines and adjuvant CMF in this patient subset. Design. Prospective cohort study. Patients. Eighty-eight breast cancer patients, stage T(3)b-T-4 abc, N0-2, M -0. Results: From February 1991 to July 1994, 88 consecutive patients with loca lly advanced breast cancer were treated at the Istituto Nazionale Tumori, M ilano, with full-dose doxorubicin (75 mg/m(2)) or epirubicin (120 mg/m(2)) for three cycles followed by surgery, adjuvant chemotherapy with i.v. CMF f or six cycles and local radiotherapy +/- Tamoxifen. A high rate of objectiv e responses (70%), but a low incidence of pathologic complete remission (2% ), were observed following primary treatment with single-agent anthracyclin es. Frequency of responses was not associated with tumor estrogen or proges terone receptors status, Mib-1 or grading. In 28 patients (32%) conservativ e surgery could be performed. At a median follow-up of 52 months, relapse f ree survival and overall survival are 52% and 62%, respectively. A multivar iate analysis demonstrated a significant favorable prognosis in patients wi th limited nodal involvement at surgery and negative Mib-1 values. This dru g sequence failed to significantly ameliorate the long term results in this unfavorable patient subset and more effective drug regimens and innovative therapeutic strategies are needed.