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...

The excess risk of distant recurrence in triple-negative breast cancers, versus other forms of cancer, is attributable in large part to an excess of visceral metastases in the first five years following diagnosis.

One of the most important factors associated with local recurrence after lumpectomy in breast cancer patients is the status of the surgical margin. Standard surgical practice is to obtain clear margins even if this requires a second surgical procedure. It is assumed that reexcision to achieve clear margins when positive margins are present at initial excision is as effective as complete tumor removal at a single procedure; however, the efficacy of reexcision in this context has not been well studied. A retrospective search of the Henrietta Banting Breast Centre database from 1987 to 1997 identified 1430 patients who underwent lumpectomy for invasive breast cancer: 1225 patients (group A) had negative margins at the initial surgery and 152 patients (group B) underwent one or more reexcisions to achieve negative margins. Fifty-three patients had positive margins at final surgery, but no reexcision was done (group C). Logistic regression was used to identify factors that were predictive of a positive margin; predictors of local recurrence in women whose tumors were completely resected were determined using Cox's proportional hazards model. Patients in groups A, B, and C differed with respect to mean age at diagnosis (58 years, 51 versus, and 56 years, respectively, p < 0.0001), mean tumor size (19 mm, 16 mm, and 26 mm, respectively, p < 0.0001), node positivity (30%, 22%, and 41%, respectively, p = 0.004), and the presence of a ductal carcinoma in situ (DCIS) component (60%, 64%, and 79%, respectively, p = 0.007). The mean follow-up period was similar for the three groups (8 years, 8 years, and 9 years, respectively, p = 0.17). Young age was the only variable predictive of positive margins. Among patients undergoing complete tumor excision, there was a suggestion of a higher 10 year local recurrence rate in reexcision group B, but the difference did not reach statistical significance (11.6% versus 16.6%, p = 0.11). Cox's multivariate regression analyses identified older age, smaller tumor size, receiving radiation therapy, and tamoxifen use as significantly decreasing the rate of local recurrence in patients with negative margins at initial surgery or after reexcision. Our data confirm the results of previous studies indicating that young age is an independent predictor of positive margins after lumpectomy for invasive breast cancer. The only independent predictor of local recurrence in our study cohort was large tumor size. There was a trend toward a higher local recurrence rate if more than one procedure was required to secure clear margins, although this effect was not independent of other factors. Reexcision to clear involved margins is an important surgical intervention for both younger and older women.