Prevalence and Prognostic Role of Triple-Negative Breast Cancer by Race: A Surveillance Study

Abstract

Introduction

Emerging research suggests a substantially greater prevalence of the adverse triple-negative (TN) subtype (human epidermal growth factor receptor [HER]2⁻, estrogen receptor [ER]⁻, and progesterone receptor [PR])⁻) among black patients with breast cancer. No reports however have been generated from a statewide cancer registry.

Patients and Methods

The study consisted of all black patients (N = 643) and a random sample of white patients (n = 719) diagnosed with primary invasive breast cancer (2000-2003) listed in the National Cancer Institute–Surveillance Epidemiology and End Results (NCI-SEER) Connecticut Tumor Registry (CTR). HER2 status was obtained from pathology reports submitted to the registry. Remaining data were obtained from the registry database.

Results

TN tumors were more prevalent in black compared with white patients (30.8% vs. 11.2%, respectively; P < .001.) There was a 2-fold greater frequency of ER⁻ and PR⁻ phenotypes among black patients, but HER2 status did not differ by race. Patients with lobular cancer were less likely to have TN breast cancer compared with patients with ductal tumors (odds ratio [OR] = 0.23; 95% confidence interval [CI], 0.10-0.58). Among patients with regional disease, black patients exhibited increased risk of death (relative risk [RR] = 2.71; 95% CI, 1.48-4.97) independent of TN status. No survival disparity was found among patients with local disease.

Discussion

These registry-based data corroborate reports that TN breast cancer varies substantially by race and histologic subtype. A survival disparity among patients with advanced disease, but not local disease, casts some doubt on TN status as an explanation for differences.

Conclusion

More research is warranted to understand why black patients with advanced breast cancer may be at increased risk for death whether or not their tumors express the TN phenotype.

Introduction

Despite consistently lower incidence rates for breast cancer, black patients have substantially higher mortality rates compared with whites.1, 2, 3, 4 Disparate outcomes are likely due to an array of socioeconomic, behavioral, and clinic factors.1, 5, 6, 7 Emerging evidence from hierarchical genome-wide classification studies also suggest that differential expression profiles may explain, in part, the mortality disparity. Four recently identified expression clusters, referred to as intrinsic subtypes, are thought to represent biologically distinct disease entities.8, 9 Of these, the basal-like subtype tends to confer a significantly worse prognosis10, 11 and has been found in an approximately 3-fold greater proportion among black patients compared with white patients.¹² This subtype is characterized by low expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); high expression of proliferative genes, such as MK167, certain basal cytokeratins (eg, CK5, CK6, CK17), and EGFR1; frequent mutations in p53 and other genes; and dysfunction of the BRCA1 gene.11, 13 The other gene clusters are HER2-enriched, characterized by high expression of HER2 yet little or no expression of hormone receptors; luminal A, characterized mostly by expression of ER and associated genes; and luminal B, which is also mostly ER-expressing but is distinguished from luminal A by a relatively high-proliferation gene signature (eg, Ki-67) and a subset positive for HER2 expression.8, 9, 14, 15

Because genomic expression profiling is not yet standard in the clinic setting, an immunohistochemical (IHC) designation known as triple-negative (TN) breast cancer (ER⁻, PR⁻, and HER2⁻) has emerged as a proxy categorization for the basal-like subtype.10, 13 Although TN breast cancer does not share many of the molecular features of the basal-like subtype, a number of studies have reported comparable associations with worse survival.¹⁰ Results from a nested case study of 476 patients from a population-based cohort derived from the Atlanta metropolitan area reported that TN breast cancers were far more prevalent among younger women, particularly younger black women.¹⁶ Hospital-based case series from the Boston area¹⁷ and Marshfield Clinic¹⁸ in Wisconsin also reported an almost tripling of TN among black patients compared with white patients.

To investigate the distributions and outcomes of TN breast cancer by race in a population-based study, we used data from the Connecticut Tumor Registry (CTR), a statewide registry in the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI). We performed a multiyear record review of 1362 patients with breast cancer, including all newly diagnosed breast cancers among black women and a comparably sized random sample of white women diagnosed during 2000-2003. To our knowledge, there have been no estimates of the prevalence and prognostic importance of the TN subtype derived from a statewide surveillance source.