Original studyPrevalence and Prognostic Role of Triple-Negative Breast Cancer by Race: A Surveillance Study
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.
Section snippets
Population
Data were obtained from the CTR, a participant site in the NCI-SEER program, on patients diagnosed with primary invasive female breast cancers (ICD-O-3 codes C500-C509) between January 1, 2000 and December 31, 2003. Of the full population of black patients with breast cancer during the study period, 96.5% (643/666) were included in analyses. Reasons for exclusions (n = 23) were duplicate records of the same case or discrepant information about racial status. A comparably sized random sample of
Results
As shown in Table 2, when compared with whites, black patients with breast cancer were diagnosed at a younger age (mean of 57.6 vs. 62.5 years, respectively; P < .001), were more likely to be < 50 years (33.1% vs. 21.1%, respectively; P < .001), and presented with higher grade (P < .001) and larger tumors (mean of 2.32 cm vs. 2.00 cm; P < .001). White patients had nearly twice the prevalence of lobular tumors (9.3% vs. 5.3%; omnibus P = .001) and a markedly lower prevalence of medullary tumors
Discussion
In this analysis from a statewide cancer registry, we found a 2- to 3-fold difference in the prevalence of TN breast cancer among blacks compared with whites, in keeping with recent hospital-based and population-based clinical studies.16, 17, 18, 29, 30 We found that the rate of TN tumors remained at about 11% for white patients both older and younger than 50 years, but varied by age among black patients (35% vs. 24%, respectively.) Our findings also are similar to previous reports that tumors
Conclusion
Our findings benefit from 4 years of data derived from a well-established, population-based, statewide cancer registry recognized for high quality and complete data.47 Still our results should be interpreted with some caution. The large proportion of missing data on HER2 status raises the prospect of bias due to an unmeasured confounder. Our prevalence and survival results, however, are consistent with earlier evidence, which offers the first supportive evidence of the general accuracy of HER2
Acknowledgments
This study was funded in part by the Holger Hansen Graduate Student Research Fellowship, awarded by the Master of Public Health program at the University of Connecticut Health Center, and the NCI SEER program contract (N01-PC-35133) at the Connecticut Tumor Registry in the Connecticut Department of Public Health (DPH). This study was approved by the DPH Human Investigations Committee. Certain data used in this publication were obtained from DPH. The authors assume full responsibility for
References (47)
Molecular portraits of breast cancer: Tumour subtypes as distinct disease entities
Eur J Cancer
(2004)- et al.
Triple-negative/basal-like breast cancer: review
Pathology
(2009) Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study
Cancer Detect Prev
(2006)- et al.
Patterns of HER2 testing in the management of primary breast cancer
Cancer Epidemiol
(2009) - et al.
Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast
Mod Pathol
(2010) - et al.
HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues
Clin Breast Cancer
(2004) - et al.
Tumor biologic factors and breast cancer prognosis among white, hispanic, and black women in the United States
J Natl Cancer Inst
(1994) - et al.
Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status
J Clin Oncol
(2006) - et al.
Racial and ethnic disparities in breast cancer mortality: are we doing enough to address the root causes?
J Clin Oncol
(2006) Surveillance Epidemiology and End Results: Cancer statistics review, 1975-2006
Impact of socioeconomic status on cancer incidence and stage at diagnosis: selected findings from the surveillance, epidemiology, and end results: national longitudinal mortality study
Cancer Causes Control
Differences in breast cancer stage, treatment, and survival by race and ethnicity
Arch Intern Med
African-American/white differences in breast carcinoma: P53 alterations and other tumor characteristics
Cancer
Molecular portraits of human breast tumours
Nature
Gene-expression signatures in breast cancer
N Engl J Med
Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study
JAMA
Triple-negative breast cancer: risk factors to potential targets
Clin Cancer Res
Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer
J Natl Cancer Inst
AJCC Cancer Staging Handbook
Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA
Breast Cancer Res Treat
Triple-negative breast cancers are increased in black women regardless of age or body mass index
Breast Cancer Res
Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival
Clin Med Res
International Classification of Diseases for Oncology
Cited by (20)
Metabolic Alterations Induced by Kudingcha Lead to Cancer Cell Apoptosis and Metastasis Inhibition
2020, Nutrition and CancerClinicopathologic Features and Survival Analysis of Non-metastatic Breast Cancer Patients in Guatemala
2020, Archives of Breast CancerBiopsychosocial Challenges and Needs of Young African American Women with Triple-Negative Breast Cancer
2018, Health and Social WorkNow is the Time for a Postracial Medicine: Biomedical Research, the National Institutes of Health, and the Perpetuation of Scientific Racism
2017, American Journal of Bioethics