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Home What is Breast Cancer Types of Breast Cancer Triple Negative Breast Cancer and Unfavorable Outcomes in African American Women, a Health Disparity

Triple Negative Breast Cancer and Unfavorable Outcomes in African American Women, a Health Disparity

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Introduction

 

Population-based studies have shown that triple negative breast cancer in African American women occurs in younger, premenopausal women.  It tends to be more aggressive, is diagnosed at a later stage, and carries poorer survival outcomes than those cancer subtypes diagnosed in Caucasian women.[1] In 2011, 26,840 new cases of breast cancer will be diagnosed in African American women with an estimated 6,040 deaths making breast cancer the most commonly diagnosed cancer and the second leading cause of cancer deaths among African American women, preceded only by lung cancer.[2] Lower socioeconomic status, delayed mammography screenings, lack of targeted therapy, and genetic expression mutations have all been identified as factors contributing to the higher prevalence of triple negative breast cancer in African American women and subsequent poorer survival outcomes.

Triple Negative Breast Cancer Characteristics

Approximately 15% of all breast cancers are triple negative breast cancers (TNBC), meaning they are negative for receptors for Estrogen (ER), Progesterone (PR), and Human Epidermal Growth Factor Receptor 2 (HER2).[3] It has been found that African Americans are three times more likely to have TNBC than other ethnic groups [3] and that 39% of all breast cancers in premenopausal African American women are TNBC.[4]

At time of diagnosis, TNBC is more frequently high grade compared to other subtypes of breast cancer with lymph node and vascular invasion and associated with distant metastases to sites such as lung (40%) and brain (30%).[5] These tumors have higher rates of genomic mutations when compared to other breast cancer subtypes which may contribute to its aggressive nature and high proliferation rate.[6] Furthermore, TNBC presents challenges to therapy.  The lack of receptor expression prevents the treatment of TNBC with traditional hormonal targeted therapies such as tamoxifen, making chemotherapy the first line of treatment.  TNBC appears to be particularly sensitive to anthracyclines and taxanes, especially in the neoadjuvant setting when a therapeutic agent is administered before a main treatment such as radiation or surgery is instituted.  Nonetheless, despite having high chemosensitivity, TNBC patients continue to have poor overall survival with recurrence of residual disease [7] most likely to occur 3 years after treatment.

While genetic analysis has lead to a better understanding of the proliferative nature of  TNBC, it still does not account for the increased frequency of occurrences of TNBC in African American women and at younger ages.

Obesity

The relationship between obesity and risk of breast cancer is largely dependent upon whether a woman is pre- or postmenopausal.  Obesity in premenopausal women appears to have a protective affect, decreasing risk, whereas obesity in postmenopausal women increases risk.[8] Extensive research has looked at the role of obesity in explaining why African American women have a greater tendency to have advanced staged breast cancer at time of diagnosis than other ethnic groups.  It has been found that when adjusting for body mass index (BMI), racial differences in staging still persist.[9] When looking specifically at TNBC, no association between BMI, age, and menopause status has been found.  This suggests there are other factors determining tumor subtype in African American women.[10]

Socioeconomic Status and Poverty

Social factors significantly impact breast cancer prevention, screening, treatment, and outcome and play a major role in the mortality rates amongst African Americans.[11] [12]

Socioeconomic status (SES) is a person’s economic and social position based upon income, education, and occupation.  Low SES has been extensively documented as a major contributing factor to health disparities [11]. A lower income level is associated with inadequate health care insurance coverage which results in a decrease in preventative health care, including physical examination and recommended health maintenance screening procedures. A further affect of low SES is an increase in comorbidities and risk factors such as poor nutrition and smoking [12].

West Africa

While taking into consideration the influence of social, economic, and cultural beliefs as well as SES, age and stage at diagnosis in the mobility and mortality of breast cancer, there continues to be a discrepancy in survivorship between African American and Caucasian women.[13] To better understand the missing link between the susceptibility of African American women and TNBC a study was conducted in 2009 analyzing 507 patients with breast cancer in West Africa.  Basal-like TNBC was found in 27% of patients.  The average age of patients was 44.8.  This study by Huo, et al. implies that the trends in TNBC seen in African American women may have a genetic etiology which lies within their African ancestry.

Discussion

Triple negative breast cancer is a complex tumor subtype that researchers continue to investigate.  Social, economic, and cultural influences contribute to the complex nature of tumor manifestation, progression, and mortality yet controlling for many of these factors, there consistently appears to be an unknown confounder that predisposes African American women to TNBC.  The most recent research has shown that this confounder may likely lie in their African ancestry.


 

- Annelyssa Johnson, MS3

 

 

REFERENCES

[1] Bauer KR et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007 May 1;109(9):1721-8.

[2] American Cancer Society. Cancer Facts & Figures for African Americans 2011-2012. Atlanta: American Cancer Society, 2011.

[3] Stead LA et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 2009;11(2):R18.

[4] Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938-48. Review.

[5]Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938-48. Review.

[6] Loo LW et al.  Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women. Breast Cancer Research & Treatment. 2011;127(1):297-308.

[7] Carey, LA et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 2007;13:2329-2334.

[8] van den Brandt PA et al.  Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. American Journal of Epidemiology 2000; 152(6):514–527.

[9] Cui Y et al. Can obesity explain the racial difference in stage of breast cancer at diagnosis between black and white women? Journal of Women’s Health and Gender-Based Medicine 2002; 11(6):527–536.

[10] Stead LA et al. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 2009;11(2):R18.

[11] Vona-Davis, L, Rose, D. The Influence of Socioeconomic Disparities on Breast Cancer Tumor Biology and Prognosis: A Review. Journal of Women's Health. 2009;18 (6): 883-893.

[12] Gerend M, Pai M. Social determinants of black-white disparities in breast cancer mortality: a review. Cancer Epidemiol Biomarkers Prev. 2008;17:2913-2923.

[13] Huo, D et al. Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. J Clin Oncol. 2009; 27(27):4515-21.