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Risk Factors for Locoregional Recurrence Among Breast Cancer Patients: Results From International Breast Cancer Study Group Trials I Through VII

From the University of Göteborg, Sahlgrenska University Hospital, Göteborg, Sweden; International Breast Cancer Study Group Statistical Center; Dana-Farber Cancer Institute and Frontier Science and Technology Research Foundation; and Harvard School of Public Health, Boston, MA; European Institute of Oncology, Milan, Italy; Oncology Institute of Southern Switzerland, Bellinzona; International Breast Cancer Study Group Coordinating Center and Inselspital, Bern; and Kantonsspital, St Gallen, Switzerland; Department of Surgery, SU/Moelndal’s Hospital, Moelndal, Sweden; Institute of Oncology, Ljubljana, Slovenia; Groote Shuur Hospital and University of Cape Town, South Africa; Australian New Zealand Breast Cancer Trials Group, Newcastle; The Cancer Council Australia and University of Sydney, Sydney; and Department of Surgery, Royal Melbourne Hospital, Victoria, Australia.

Address reprint requests to Arne Wallgren, MD, Department of Oncology, University of Göteborg, Sahlgrenska University Hospital, S 413 45 Göteborg, Sweden; email: arne.wallgren{at}oncology.gu.se.

Purpose: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies.

Patients and Methods: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months’ duration and/or tamoxifen. Median follow-up is 12 to 15.5 years.

Results: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women.

Conclusion: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.

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