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Site of Primary Tumor Has a Prognostic Role in Operable Breast Cancer: The International Breast Cancer Study Group Experience

Marco Colleoni, David Zahrieh, Richard D. Gelber, Stig B. Holmberg, Jan E. Mattsson, Carl-Magnus Rudenstam, Jurij Lindtner, Darja Eren, Raymond Snyder, John Collins, Martin F. Fey, Beat Thürlimann, Diana Crivellari, Elizabeth Murray, Caesar Mendiola, Olivia Pagani, Monica Castiglione-Gertsch, Alan S. Coates, Karen Price, Aron Goldhirsch

From the European Institute of Oncology, Milan; Centro di Riferimento Oncologico, Aviano, Italy; International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute and Frontier Science and Technology Research Foundation, Boston, MA; Department of Surgery, SU/Moelndal's Hospital, Moelndal; West Swedish Breast Cancer Study Group, Sahlgrenska University Hospital, Göteborg, Sweden; The Institute of Oncology, Ljubljana, Slovenia; Department of Oncology, St Vincent's Hospital; Department of Surgery, The Royal Melbourne Hospital, Melbourne; The Cancer Council Australia and University of Sydney, Sydney, Australia; Institute of Medical Oncology, Inselspital; International Breast Cancer Study Group Coordinating Center, Bern; Kantonsspital, St Gallen; Oncology Institute of Southern Switzerland, Lugano, Switzerland; Groote Schuur Hospital and University of Cape Town, South Africa; Madrid Breast Cancer Group, Madrid, Spain.

Address reprint requests to Marco Colleoni, MD, Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; e-mail: marco.colleoni{at}ieo.it

PURPOSE: Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease.

PATIENTS AND METHODS: Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years.

RESULTS: A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS).

CONCLUSION: Tumor site has a significant prognostic utility, especially for axillary lymph node–negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.

Presented at the 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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