Purpose: To compare the clinical features, natural history, and outcomes for women with ''triple-negative'' breast cancer with women with other types of breast cancer. Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triplenegative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative. The prognostic significance of triple-negative breast cancer was explored. Results: The median follow-up time of the 1,601women was 8.1years. One hundred and eighty of 1,601 patients (11.2%) had triple-negative breast cancer. Compared with other women with breast cancer, those with triple-negative breast cancer had an increased likelihood of distant recurrence (hazard ratio, 2.6; 95% confidence interval, 2.0-3.5; P < 0.0001) and death (hazard ratio, 3.2; 95% confidence interval, 2.3-4.5; P < 0.001) within 5 years of diagnosis but not thereafter. The pattern of recurrence was also qualitatively different; among the triple-negative group, the risk of distant recurrence peaked at f3 years and declined rapidly thereafter. Among the ''other''group, the recurrence risk seemed to be constant over the period of follow-up. Conclusions: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.The heterogeneous nature of breast cancer has implications for physicians and their patients. Increasingly, treatments are targeted toward molecular markers. The development of hormonal therapies validated the distinction between estrogen receptor (ER)-positive and ER-negative breast cancers. Tamoxifen was initially used as a treatment for all breast cancers, but it was later recognized that only patients with tumors that express hormone receptors benefit from tamoxifen. The introduction of trastuzumab therapy (Herceptin) highlighted the importance of identifying tumors with amplified or overexpressed HER2neu (HER2). Gene expression studies using DNA microarrays have identified subtypes of breast cancer that were not apparent using traditional histopathologic methods (1). Four common subtypes have been identified; two of these are derived from ER-negative tumors (basal-like and HER2 positive) and two are derived from ER-positive tumors (luminal A and B; refs. 2, 3). Basal-like breast cancers are overrepresented in African-American women (4) and in BRCA1 mutation carriers (5, 6).Perou et al. (1) reported that women with basal-like breast cancers had shorter relapse-free survival times than women with other types of breast cancer. Basal-like breast cancers also have a tendency toward visceral (versus bone) metastasis (7,8). In an analysis of 49 patients with basal-like breast cancer and 49 matched controls, Banerjee et al. (9) found that patients with basal-like breast cancer had significantly shorter diseasefree and overall survival times than women with other tumors, but...

neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

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