Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). TNBC constitutes about 15–30 percent of all diagnosed invasive breast cancer cases in the United States. African-American (AA) women have high prevalence of TNBC with worse clinical outcomes than European-American (EA) women. The contributing factors underlying racial disparities have been divided into two major categories based on whether they are related to lifestyle (non-biologic) or unrelated to lifestyle (biologic). Our objective in the present review article was to understand the potential interactions by which these risk factors intersect to drive the initiation and development of the disparities resulting in the aggressive TNBC subtypes in AA women more likely than in EA women. To reach our goal, we conducted literature searches using MEDLINE/PubMed to identify relevant articles published from 2005 to 2019 addressing breast cancer disparities primarily among AA and EA women in the United States. We found that disparities in TNBC may be attributed to racial differences in biological factors, such as tumor heterogeneity, population genetics, somatic genomic mutations, and increased expression of genes in AA breast tumors which have direct link to breast cancer. In addition, a large number of non-biologic factors, including socioeconomic deprivation adversities associated with poverty, social stress, unsafe neighborhoods, lack of healthcare access and pattern of reproductive factors, can promote comorbid diseases such as obesity and diabetes which may adversely contribute to the aggression of TNBC biology in AA women. Further, the biological risk factors directly linked to TNBC in AA women may potentially interact with non-biologic factors to promote a higher prevalence of TNBC, more aggressive biology, and poor survival. The relative contributions of the biologic and non-biologic factors and their potential interactions is essential to our understanding of disproportionately high burden and poor survival rates of AA women with TNBC.

Highlights

  • Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women in the United States [American Cancer Society

  • The reasons underlying the racial disparity in breast cancer outcome are multifactorial

  • Breast cancer risk factors have been divided into two major categories based on whether they are related to lifestyle or related to factors unrelated to lifestyle

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Summary

INTRODUCTION

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women in the United States [American Cancer Society. Breast cancer is a heterogeneous disease consisting of distinct biological subtypes with a range of clinical, pathological, molecular, and genetic features and differing therapeutic responses and outcomes including the Black-White disparities in outcome [1] These differences have been demonstrated by molecular classification based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). A recent population study in the United States has described four molecular breast cancer subtypes as mentioned above, based on the expression of three tumor markers, namely estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) [5, 6]. The present review is undertaken to provide a comprehensive view of how these factors contribute to marked differences in age of onset, stage of presentation and survival between AA and NH White women and eventually the development and outcome of the TNBC disparity. The article will provide comprehensive view of the relationship between biological and non-biological factors to facilitate our understanding of disparities in the risk of TNBC, and to guide future efforts to eliminate such disparities

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