Genomics: Insight

Hypothesis: This literature review aims to explain the impact of social determinants of health on breast cancer outcomes for Hispanic/Latina women, including their representation in genomic databases and participation in genetic testing for breast cancer research.

I. Introduction

The Hispanic/Latino community is the fastest-growing racial group in the United States and is predicted to grow 60% by 2050¹. For the purpose of this essay, we will use the term Hispanic/Latino for overlapping but distinct identities to refer to individuals from Spanish-speaking countries and countries in Latin America, regardless of language. In the US, 1 in 8 women will develop breast cancer in their lifetime, and incidence is increasing by 0.5% annually². As in women from other racial groups, breast cancer is a leading cause of cancer death for Hispanic/Latina women³. Although Hispanic/Latina women tend to have a similar incidence of breast cancer compared to non-Hispanic white (NHW) women, they are more frequently diagnosed with later stages of cancer and have 1.4-fold higher mortality rates⁴. The manifestation of breast cancer is complex and results from the interplay of genetic and environmental factors. Social determinants of health, like lower socioeconomic status (SES), education level, neighborhood safety, access to healthcare, etc., together with underlying health conditions and family history and genetics³, play a significant role in breast cancer outcomes. Despite the prevalence and severity of breast cancer disease for the growing Hispanic/Latina women population, the genetic underpinnings of their breast cancer are understudied, especially in the areas of genomics and precision medicine⁵. This literature review aims to explain the impact of social determinants of health on breast cancer outcomes for Hispanic/Latina women, including their representation in genomic databases and participation in genetic testing for breast cancer research.

II. Social Determinants of Health (Hispanic women)

The greatest contributors to health disparities worldwide are social determinants of health (SDOH), defined as economic, environmental, political, and social conditions in which people live that dictate the access and quality of healthcare people receive⁶. Lower socioeconomic status plays a crucial role in health disparities and is associated with poorer breast cancer outcomes across all ethnicities⁷. African Americans and Hispanics/Latinos constitute a larger percentage of their population below the poverty line compared to other racial and ethnic groups 8. Approximately 16.7% of Hispanics/Latinos live beneath the poverty line compared to 9.5% of their white counterparts 8. Low-income populations have a higher prevalence of health conditions such as obesity, diabetes, hypertension, and cardiovascular disease related to lower consumption of healthy foods and higher sedentary behavior, amongst other factors 9.

Obesity increases the risk of breast cancer development through several mechanisms, including the excess amount of estrogen produced by adipose tissue, increased development of type 2 diabetes caused by higher levels of insulin resistance, and greater DNA damage as a result of inflammation-induced oxidative stress^10,11. Hispanic/Latino adults in the US have a higher prevalence of obesity (47%) when compared to NHW (38%)⁶. A study revealed that the 5-year survival rate for obese women with breast cancer was 55.6% compared with 79.9% for women with normal weight⁹. Obese women had larger tumors with higher rates of lymphatic invasion and nodal involvement. This finding is likely the result of the negative effects of obesity in cancer genesis and behavior. Nevertheless, it is also important to mention that in some older studies obese women may have received relatively lower doses of chemotherapy which can contribute to poorer outcomes for these women⁹.

Compared to NHW women, Hispanic/Latina women have a higher prevalence of “triple-negative” breast cancer^3,12. Triple-negative tumors behave aggressively and are more challenging to treat due to the lack of specific receptors to target. They grow faster and metastasize to other sites more often than receptor-positive tumors¹³ (tumors expressing estrogen, progesterone, or HER2 receptors)¹⁴. Social determinants of health and, more specifically, low socioeconomic status affect not only the incidence of breast cancer but also its severity. Banegas et al. have reported on the correlation between low socioeconomic status and breast cancer subtype as a surrogate of disease severity that determines cancer behavior and the likelihood of response to standard cancer therapies^15,21. They found that Hispanic/Latina women from lower socioeconomic status (SES) have a 1.32-1.42 fold increased risk of triple-negative tumors when compared to Latinas from higher SES 15. This increased risk likely contributes to poorer outcomes associated with lower SES seen in Hispanic/Latina women with breast cancer.

Access to healthcare in the United States relies heavily on having healthcare insurance coverage. People of Hispanic/Latino descent are the least insured group in the United States¹⁶. The CDC reported that in 2023, 1 in 4 Hispanic adults (18-64) lacked health insurance¹⁷. Low rates of medical insurance result in decreased access to quality healthcare; as a consequence, Hispanic/ Latina women are less likely to undergo regular screening mammogram exams compared to women of other ethnicities, leading to an increase in late-stage diagnosis¹⁸. Women with breast cancer who lack health insurance are also at a higher risk of receiving suboptimal cancer care¹⁸. In one study, 23% of Hispanic/Latina women, compared with 16% of NHW women, did not receive adjuvant therapy as part of their breast cancer treatment plan19. These minority women were more likely to have a higher number of comorbidities due to lack of health insurance¹⁹. For Hispanic/Latina women, the lack of medical insurance coverage does not only affect their ability to receive cancer care but also negatively impacts access to genetic testing and enrollment in genetic databases²⁰.

Social determinants of health and, more specifically, disadvantaged socioeconomic factors affect not only the incidence of breast cancer but also its severity.

III. Representation of Hispanic/Latina Women in Genomic Research

The Cancer Genome Atlas (TCGA) is a genomic database created by the National Cancer Institute²¹. The genomic data includes the genetic makeup of tissue from several cancer types, including breast cancer²². When the data from the TCGA database was analyzed, it was clear that Hispanic/Latina women were grossly underrepresented compared to the general population and that NHW women were overrepresented⁵. Currently, Hispanics/Latinos comprise 19.5% of the US population, while NHW makes up 58.4% 23. In the TCGA database, only 3% of breast cancer data was obtained from Hispanic/Latina women, and 75.7% of that data came from NHW women^5,24. With the rapid growth of genomic technology and its applications to cancer research and treatment within the realm of precision medicine, it is vital to make sure that all ethnic groups are properly represented if they are to benefit from these technologies. Underrepresentation of Hispanic/Latinas in genetic databases will result in insufficient data for developing precision medicine therapies tailored to this demographic. A study found that while there are high levels of interest in genomic medicine across many racial groups, factors including the lack of familiarity with genomic screening, higher uninsured rates, lower socio-economic status, and mistrust in the healthcare system and institutions are all likely contributors to the continued underrepresentation of minority groups²⁵. Reports on the impact of cultural and spiritual beliefs show that they can also be barriers for Hispanics/Latinas to access breast cancer screening and care, which results in treatment delays²⁶. These factors may also explain the lower representation of Hispanic/Latina women in cancer databases resulting from decreased access to and participation in genetic testing.

IV. Cell and Molecular Foundations of Breast Cancer

Precision medicine is becoming an increasingly important component in cancer treatment²⁷. Breast cancer presents in a variety of ways in different individuals and genomic composition determines the tumor type. While breast cancer is diagnosed based on clinical presentation and screening imaging studies, such as mammograms, the subtype of breast cancer can be identified through immunohistochemistry and genetic analysis²⁷. Breast cancer subtypes present unique molecular features and are characterized by the presence of hormone receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)¹⁴. Tumors with higher expression of ER are typically subclassified as Luminal A or B, based on the presence or absence of HER2, which differentiates the two subtypes respectively¹². ER-/PR- tumors can be subclassified as HER2+ or HER2-14. The latter is most commonly described as triple-negative, signifying the absence of all three hormonal receptor biomarkers¹⁴. As a result of the lack of all hormonal receptors, triple-negative tumors are more difficult to target and treat with standard therapies and, therefore, tend to have the worst prognosis²¹.

As stated earlier, the prevalence of triple-negative tumors in Hispanic/Latina women is higher than in other races and ethnicities^3,12. In 2020, Philipovskiy and colleagues conducted a study identifying the most prevalent biomarker mutations in Hispanic/Latina women²⁸. They found that four individual biomarkers in this group mutated at statistically significant higher rates than in NHW, African American, and Asian women²⁸. Finding higher prevalence of specific biomarker mutations in different racial groups highlights the importance of including women of

all racial and ethnic groups in research and genomic databases. Ensuring proper representation can inform further research for precision treatments.

V. Conclusion

The Hispanic/Latino community is the fastest growing racial/ethnic group in the US¹. Social determinants of health such as low SES and education level, lack of health insurance together with higher prevalence of obesity and greater number of comorbidities are important factors contributing to poor outcomes for Hispanic/Latina women with breast cancer. As discussed, approximately 16.7% of Hispanics/Latinos live beneath the poverty line 8 which is correlated with 1.32-1.42 fold risk of developing triple-negative tumors¹⁵. These tumors behave more aggressively and are difficult to target with standard therapies²¹. Hispanic/Latinos represent the largest segment of uninsured individuals in our country with 1 in 4 Hispanic adults (18-64) lacking health insurance 17, causing significant barriers to accessing and receiving care ¹⁶. Our review highlights the underrepresentation of Hispanic/Latina women in the TCGA genomic database which is largely explained by the factors mentioned above. We hope this review adds to the body of evidence of the healthcare disparities affecting Hispanic/Latina women living with breast cancer and encourages further development of strategies to increase their representation in genomic studies and to close disparity gaps in breast cancer care and accessibility. Initiatives like the National Human Genome Research Institute’s projects to enhance equity and inclusivity by addressing and mitigating specific barriers to diverse participation in genomic research will hopefully result in improved health outcomes for all²⁹.

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