Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide

Abstract

BACKGROUND Locally advanced breast carcinoma is associated with a poor prognosis. With single treatment modalities, i.e., surgery and/or radiation therapy, results have been consistently dismal. However, several earlier reports have indicated improvement in survival with a combined modality approach, i.e., the utilization of systemic therapy. METHODS Between 1991 and 1994, 128 patients with locally advanced noninflammatory or inflammatory breast carcinoma (LABC) were treated with a combined modality strategy consisting of 4‐6 courses of preoperative 5‐fluorouracil (600 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (FEC) every 3 weeks, followed by modified radical mastectomy or sector resection with axillary dissection in combination with postoperative radiotherapy and concomitant cyclophosphamide (850 mg/m2). Postoperatively, 3‐5 adjuvant courses of FEC therapy were given. Nine percent of the patients received preoperative radiotherapy because the FEC therapy was not sufficiently effective. One‐third of the patients were given tamoxifen (20 or 40 mg daily) at the end of the multimodal therapy. RESULTS Clinical responses were observed in 60% of the patients; 5% had complete responses (CR) and 55% had partial responses (PR). Stable disease (SD) was observed in 40%. No patient had progressive disease (PD) preoperatively. With a median follow‐up of 37 months, the median disease free survival (DFS) and median overall survival (OS) were 29 and 54 months, respectively. The actuarial 5‐year DFS and OS were 36% and 49%, respectively. The locoregional recurrence rate was 20%, and 53% of the patients experienced systemic relapse. Univariate analysis revealed a significant prognostic difference according to clinical stage of LABC in favor of less advanced stages. Clinical and biologic parameters linked to a significantly worse prognosis were the presence of inflammatory breast carcinoma and peau d'orange. There was a significant trend of worse prognosis for patients receiving below 60% and 75% of the intended dose intensity with reference to DFS and OS, respectively. CONCLUSIONS Standard dose preoperative and postoperative FEC therapy combined with surgery and radiotherapy in the era of mammography screening seem to yield results comparable to those achieved with other conventional strategies in the treatment of unscreened populations. Cancer 1998;83:936‐947. © 1998 American Cancer Society.

Prediction of outcome in locally advanced breast cancer by post-chemotherapy nodal status and baseline serum tumour markers

“…The clinical characteristics of our patient population with LABC largely resemble those of previous reports (Fein et al, 1994;Karlsson et al, 1998), except for the relatively high rate of hormone receptor-positive tumours (67%). However, this last figure should be viewed with caution, as hormone receptors were examined in only two-thirds of the cases, either because the tumours were unoperated or complete pathological response was achieved.…”

“…Some authors have argued against the inclusion of patients with IBC in studies of LABC because of their clearly worse outcome (Karlsson et al, 1998). In our study, too, inflammatory changes were associated with a significant decrease in 5-year survival rates from 79 to 27% (P=0.000) (Figure 1).…”

“…Two studies identified the prognostic importance of neoadjuvant treatment itself. Karlsson et al (1998) found that worse OS and DFS were associated with the receipt of less than 75 and 60%, respectively, of the intended dose intensity. In a phase II study, Honkoop et al (1998) noted a detrimental effect of a lower number of preoperative chemotherapy cycles.…”

The Efficacy of Primary Surgery Compared to Post Chemotherapy Surgery for Patients with Locally Advanced Breast Cancer

“…surgery, and/or radiotherapy, results has been consistently dismal (Karlesson et al, 1998). The appropriate management of locally advanced breast cancer is controversial, the trends towards a more effective means of improving response rates and survival have shifted to earlier aggressive treatment and the strength in the management of LABC lies in the team approach to multimodality care .…”

Biological Concepts of Prolonged Neoadjuvant Treatment plus GM-CSF in Locally Advanced Tumors

“…Generally three to four preoperative chemotherapy cycles are administered followed by a number of postoperative chemotherapy 498 Biological Concepts in Neoadjuvant Treatment cycles. The reported clinical response rates vary between 30% and 80% with 10%-30% clinical complete remissions and long-term survival in 15% of the patients [3][4][5][6]. Highdose chemotherapy with autologous stem cell support further improved disease-free survival (DFS) to a reported 64% after 30 months [7] but has yet to be shown to improve OS.…”