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High Local Recurrence Risk After Breast-Conserving Therapy in Node-Negative Premenopausal Breast Cancer Patients Is Greatly Reduced by One Course of Perioperative Chemotherapy: A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study

From the Departments of Clinical Oncology, Surgery, Pathology, and Medical Statistics, Leiden University Medical Center, Leiden; Department of Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; and European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group (Data Center, Brussels, Belgium, and member institutions).

Address reprint requests to Marc J. van de Vijver, Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands; email mvijver{at}nki.nl

PURPOSE: Patients with invasive breast cancer may develop a local recurrence (LR) after breast-conserving therapy (BCT). Younger age has been found to be an independent risk factor for LR. Within a group of premenopausal node-negative breast cancer patients, we studied risk factors for LR and the effect of perioperative chemotherapy (PeCT) on LR.

PATIENTS AND METHODS: The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare surgery followed by one course of PeCT (fluorouracil, doxorubicin, and cyclophosphamide) with surgery alone. From patients treated on this trial, we selected premenopausal patients with node-negative breast cancer who were treated with BCT to examine whether histologic characteristics and the expression of various proteins (estrogen receptor, progesterone receptor, p53, Ki-67, bcl-2, CD31, c-erbB-2/neu) are risk factors for subsequent LR. Also, the effect of one course of PeCT on the LR risk (LRR) was studied.

RESULTS: Using multivariate analysis, age younger than 43 years (relative risk [RR], 2.75; 95% confidence interval [CI], 1.46 to 5.18; P = .002), multifocal growth (RR, 3.34; 95% CI, 1.27 to 8.77; P = .014), and elevated levels of p53 (RR, 2.14; 95% CI, 1.13 to 4.05; P = .02) were associated with higher LRR. Also, PeCT was found to reduce LRR by more than 50% (RR, 0.47; 95% CI, 0.25 to 0.86; P = .02). Patients younger than 43 years who received PeCT achieved similar LR rates as those of patients younger than 43 years who were treated with BCT alone.

CONCLUSION: In premenopausal node-negative patients, age younger than 43 years is the most important risk factor for LR after BCT; this risk is greatly reduced by one course of PeCT. The main reason for administering systemic adjuvant treatment is to improve overall survival. The important reduction of LR after BCT is an additional reason for considering systemic treatment in young node-negative patients with breast cancer.

Presented at the European Cancer Conference ECCO 10, September 1999, Vienna, Austria.

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