Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network

Abstract

Background: The objective of this study was to describe clinicopathologic features, patterns of recurrence, and survival according to breast cancer subtype with a focus on triple-negative tumors.

Methods: In total, 15,204 women were evaluated who presented to National Comprehensive Cancer Network centers with stage I through III breast cancer between January 2000 and December 2006. Tumors were classified as positive for estrogen receptor (ER) and/or progesterone receptor (PR) (hormone receptor [HR]-positive) and negative for human epidermal growth factor receptor 2 (HER2); positive for HER2 and any ER or PR status (HER2-positive); or negative for ER, PR, and HER2 (triple-negative).

Results: Subtype distribution was triple-negative in 17% of women (n = 2569), HER2-positive in 17% of women (n = 2602), and HR-positive/HER2-negative in 66% of women (n = 10,033). The triple-negative subtype was more frequent in African Americans compared with Caucasians (adjusted odds ratio, 1.98; P < .0001). Premenopausal women, but not postmenopausal women, with high body mass index had an increased likelihood of having the triple-negative subtype (P = .02). Women with triple-negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs 48%; P < .0001) and were more likely to present with higher tumor classification, but they were less likely to have lymph node involvement. Relative to HR-positive/HER2-negative tumors, triple-negative tumors were associated with a greater risk of brain or lung metastases; and women with triple-negative tumors had worse breast cancer-specific and overall survival, even after adjusting for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy (overall survival: adjusted hazard ratio, 2.72; 95% confidence interval, 2.39-3.10; P < .0001). The difference in the risk of death by subtype was most dramatic within the first 2 years after diagnosis (overall survival for 0-2 years: OR, 6.10; 95% confidence interval, 4.81-7.74).

Conclusions: Triple-negative tumors were associated with unique risk factors and worse outcomes compared with HR-positive/HER2-negative tumors.

Figure 1

Overall Survival by Tumor Subtype (HR+/HER2− versus Triple Negative) Adjusting for Age, Stage, Race, Receipt of Chemotherapy, Tumor Size, Histologic Grade and Nodal Status

Figure 2

Hazard Ratios for Triple Negative versus HR+/HER2− Tumors (n=12024)* *Sample excludes patients with missing tumor size data (n=562) and patients with nodal status not assessed (n=16) **Proportional hazards regression model adjusted for age (<50, ≥50), stage (I, II, III), race (Caucasian, AA, Other), chemotherapy (Y/N), tumor size (≤2cm, >2cm), histologic grade (Low/Int, High, Unknown) and nodal status (positive, negative).