Risk Factors contributing to Methylation Shifts in BRCA1 and associated genes in African Americans with Triple Negative Breast Cancer

Rationale. Breast cancer (BC) has been recognized to be the most common type of cancer in women all over the world. One of the most aggressive subtype of BC is the triple negative breast cancer (TNBC) which is defined by the absence of estrogen receptor (ER) and progesterone receptor (PR) as well as the lack of overexpression of the human epidermal growth factor 2 (HER 2). Aim. As the estrogen and progesterone receptors as well as the expression of HER2 are lacking, a targeted therapy with anti-hormone agents and anti-HER2 cannot be utilized, the therapeutic possibilities for TNBC women are limited. The aim of this review is to present the current scientific data as well as the latest research in TNBC with focus on the risk factors as well as the current role of platinum-based chemotherapeutic agents and their future implications in TNBC treatment. Method. Information about the risk factors associated to TNBC as well as the chemotherapeutic regimens was searched through Pubmed and Medline using controlled vocabulary (e.g. breast cancer) and key words (e.g. neoadjuvant, triple negative, platinum). Systematic reviews, randomized and controlled clinical trials were analyzed. No restrictions regarding date or language were used. Conclusions. TNBC is a complex and heterogeneous disease, divided into many subtypes and with an aggressive evolution. Premenopausal women and African American women are far more likely to develop TNBC. More research is required in order to confirm the association between obesity, BMI, parity, use of oral contraceptives, alcohol and cigarette smoking and TNBC. Randomized clinical trials presented at the San Antonio Symposium suggest that platinum chemotherapy play an important role in the treatment of TNBC, especially early stage TNBC. Tumor-based measures of genomic instability will help to clarify the optimal use and activity of platinum in TNBC. However, it is clear than more epidemiological studies as well as the discovery of novel therapeutic possibilities are mandatory in order to unravel the complexity of this BC subtype, hence offering a chance to women diagnosed with TNBC.

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Racial Disparities in Triple Negative Breast Cancer: A Review of the Role of Biologic and Non-biologic Factors

Frontiers in Public Health ◽

10.3389/fpubh.2020.576964 ◽

2020 ◽

Vol 8 ◽

Author(s):

Om Prakash ◽

Fokhrul Hossain ◽

Denise Danos ◽

Adam Lassak ◽

Richard Scribner ◽

...

Keyword(s):

Breast Cancer ◽

United States ◽

Risk Factors ◽

Racial Disparities ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

The United States ◽

Poor Survival ◽

Potential Interactions ◽

Biologic Factors

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.

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