Originally published as JCO Early Release 10.1200/JCO.2006.06.5664 on November 20 2006

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Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer

Bruce G. Haffty, Qifeng Yang, Michael Reiss, Thomas Kearney, Susan A. Higgins, Joanne Weidhaas, Lyndsay Harris, Willam Hait, Deborah Toppmeyer

From the Departments of Radiation Oncology, Medical Oncology, and Surgery, Cancer Institute of New Jersey, Robert Wood Johnson Medical School–University of Medicine and Dentistry of New Jersey, New Brunswick, NJ; and Department of Therapeutic Radiology and Section of Medical Oncology, Yale University School of Medicine, New Haven, CT

Address reprint requests to Bruce G. Haffty, MD, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195 Little Albany St, New Brunswick, NJ 08903-2681; e-mail: hafftybg{at}umdnj.edu

PURPOSE: To determine the prognostic significance of triple negative breast cancers with respect to locoregional relapse and distant metastasis in conservatively managed breast cancer patients.

PATIENTS AND METHODS: A database of conservative managed (conservative surgery followed by radiation) patients, in whom all three markers (estrogen receptor, progesterone receptor, and HER2/neu) were available, was reviewed. Patients were classified as triple negative if they tested negative for all three markers. Of 482 patients with all three markers available, 117 were classified as triple negative.

RESULTS: As of September 2005, with a median follow-up time of 7.9 years, of the 482 patients in the study, there have been 53 in-breast relapses, 10 nodal relapses, 77 distant relapses, and 69 deaths. At 5 years, the triple negative cohort had a poorer distant metastasis-free rate compared with the other subtypes (67% v 82%, respectively; P = .002). Triple negative subtype was an independent predictor of distant metastasis (hazard ratio = 2.14; 95% CI, 1.31 to 3.53; P = .002) and cause-specific survival (hazard ratio = 1.79; 95% CI, 1.03 to 3.22; P = .047). There was no significant difference in local control between the triple negative and other subtypes (83% v 83%, respectively). Of 99 BRCA-tested patients in this cohort, 10 had deleterious mutations in BRCA1, and seven had mutations in BRCA2. Of 10 BRCA1 patients, eight were triple negative, whereas only one of seven BRCA2 patients was triple negative (P < .001).

CONCLUSION: Patients classified as triple negative have a poor prognosis. However, there was no evidence that these patients are at higher risk for local relapse after conservative surgery and radiation. Patients with BRCA1 mutations develop predominantly triple negative tumors.

published online ahead of print at www.jco.org on November 20, 2006.

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

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