Mapping Breast Cancer to Racial Disparities

Asian, African, and white women's breast cancers have significantly diverse cellular, microbiological, and genetic traits that could be utilized to tailor care or predict disease development. The researchers discovered potential race-specific microbiological biomarkers of breast cancer that linked with genes implicated in tumor aggressiveness, blood vessel expansion, tumor cell migration and metastasis, and the cancer pathways GLI1 and Notch.

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Racial Disparities in Breast Cancer

"The factors governing racial disparities in breast cancer are multifactorial and can include socioeconomic status, access to primary care, timely referrals, and health and nutrition," says senior study author Dipali Sharma, Ph.D., professor of oncology at the Johns Hopkins University School of Medicine and a John Fetting Fund for Breast Cancer Prevention researcher (1^✔ ✔Trusted Source
Concomitant analyses of intratumoral microbiota and genomic features reveal distinct racial differences in breast cancer

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"However, it is important to identify additional modifiers for these differences. Our study demonstrates that the microbiome and immune microenvironment of breast tumors also vary significantly among women of different ethnicities and could potentially be used as biomarkers to predict disease progression or response to treatment."

Sharma and colleagues looked at genomic and metagenomic data from the Cancer Genome Atlas cohort, which included 1,018 patients with breast cancer who were self-identified as Asian (65 patients), Black (257 patients), or White (696 patients).

Scientists used a web-based program called xCell to evaluate the patients' distinctive 64-cell signatures of breast cancer and discovered that 11 of the cell types revealed very distinct, statistically significant differences between races. Tumors from black and white women had the most obvious cellular changes, while tumors from Asian and black women had the least distinct differences.

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Do Fat Cells Influence Breast Cancer?

Researchers also discovered a higher number of smooth muscle cells in Asian women's tumors than in black women's malignancies. Adipocytes (cells that make up fat tissue) accumulated the least in Asian women's tumors but much more in white women's tumors. The proportion of hematopoietic stem cells — cells that give rise to all blood and immune cells—was much lower in Asian women's tumors compared to white women's tumors, whereas MEPs and Th1 cells were significantly greater in Asian women's cancers.

Interferon-gamma, a substance important for immunity against infections, was higher in tumors from Asian women, while CXCL9, a substance that plays a role in immune activation, was overexpressed in tumors from Black women. Together, the tumor microenvironment-related changes observed in the tumors of Black women may support aggressive tumor progression.

In studies examining the bacterial community composition of these tumors, researchers discovered that breast tumor germs in Asian women did not differ significantly from those seen in Black or white women.

Yet, the microbial compositions of breast cancers from Black and white women differed dramatically. Microbial biomarkers Acinetobacter, Citrobacter, Enterobacter, Staphylococcus, Paracoccus, and Akkermansia were more abundant in breast cancers from Black women than in those from white women, while Actinomyces and Veillonella were more abundant in white women's breast tumors than in Black women's. Among the microbiological indicators identified in Asian women were Pseudomonas and Methylobacter.

Several pathways and processes were also expressed differently in the three race groups' malignancies. Many carcinogenic pathways, including mTOR signaling, calcium signaling, Notch, and WNT, were found to be considerably elevated in the malignancies of Black women. ABC transporters, which are known to be involved in the development of chemotherapy resistance in breast malignancies, were also shown to be overexpressed in tumors from Black women.

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Gene Expression Expresses Malignancies

Using gene expression profiles, researchers discovered 394 differently expressed genes in malignancies among Asian women versus Black women. There were 381 differences between Black women and white women and 127 differences between Asian women and white women.

Finally, researchers examined for links between genes and microbial biomarkers, discovering that the gene GLI1 was associated with a type of bacterium known as Terrabacter in tumors from Asian and Black women. According to first author Sheetal Parida, Ph.D., a research associate in the Department of Oncology at Johns Hopkins University School of Medicine, these findings suggest a possible function for microorganisms in tumor blood vessel growth and merit additional investigation.

The group is planning to validate its findings in a larger cohort. They also want to determine how microbes in breast tumors affect disease progression, which could be via secreted metabolites, Sharma says, and to develop microbe-based biomarkers: "The study paves the path for further explorations as we try to understand this whole network more mechanistically."

Reference:

1. Concomitant analyses of intratumoral microbiota and genomic features reveal distinct racial differences in breast cancer - (https://pubmed.ncbi.nlm.nih.gov/36702853/)

Source-Medindia