Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity.

Yuan Chun Ding,Yuan Yuan,Joanne Mortimer,Susan L Neuhausen,Charles Warden,Linda Steele,Sharon Wilczynski

doi:10.18632/oncotarget.26559

Abstract

Molecular subtypes of triple negative breast cancer (TNBC) are associated with variation in survival and may assist in treatment selection. However, the association of patient race or ethnicity with subtypes of TNBC and clinical outcome has not been addressed. Using nCounter Gene Expression Codesets, we classified TNBCs into subtypes: basal-like immune-activated (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) in 48 Hispanic, 12 African-American, 21 Asian, and 34 White patients. Mean age at diagnosis was significantly associated with subtype, with the youngest mean age (50 years) in MES and the oldest mean age (64 years) in LAR (p < 0.0005). Subtype was significantly associated with tumor grade (p = 0.0012) and positive lymph nodes (p = 0.021), with a marginally significant association of tumor stage (p = 0.076). In multivariate Cox-proportional hazards modeling, BLIS was associated with worst survival and LAR with best survival. Hispanics had a significantly higher proportion of BLIS (53%, p = 0.03), whereas Asians had a lower proportion of BLIS (19%, p = 0.05) and a higher proportion of LAR (38%, p = 0.06) compared to the average proportion across all groups. These differences in proportions of subtype across racial and ethnic groups may explain differences in their outcomes. Determining subtypes of TNBC facilitates understanding of the heterogeneity of the TNBCs and provides a foundation for developing subtype-specific therapies and better predictors of TNBC prognosis for all races and ethnicities.

Highlights

Women who present with triple negative breast cancer (TNBC) have worse prognoses than those with other breast cancer subtypes
There was a marginally statistically significant association (p = 0.06) for positive lymph nodes where 43% of Asians had positive lymph nodes compared to an average of 23% across all 115 TNBC cases
This is important given that Hispanics and Asians are fast-growing populations in the United States; they have been largely underrepresented in genomic studies of cancer

Summary

Introduction

Women who present with triple negative breast cancer (TNBC) have worse prognoses than those with other breast cancer subtypes. Defined as breast cancer that lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), TNBC is an aggressive histological subtype of breast cancer where women present with high grade, advanced disease. Compared to other types of breast cancer, women with TNBC develop recurrent disease early and often to visceral sites. TNBC is sensitive to chemotherapy but responses are short-lived and median survival for those with metastatic disease is only 12 months [2]. TNBC accounts for 10–25% of all invasive breast cancers depending on race and ethnicity. In a 2010 study of 57,483 breast cancer patients from 17 population-based registries participating in the Surveillance, Epidemiology, and End Results (SEER) program, African-American women were twice as likely and Hispanic women were www.oncotarget.com

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Conclusion