Decode cause of aggressive breast cancer in Women of Color

Last Updated on December 27, 2024 by Joseph Gut – thasso

December 26, 2024 – Breast cancer is the second most common cancer in women, with 297,790 estimated new cases in the United States in 2023. The relatively high 5-year overall survival of 90.8% indicates that the disease is curable. The advanced stage at the diagnosis and limited access to treatment options contribute to 43,000 annual deaths; triple-negative breast cancer (TNBC) remains the major cause of mortality in breast cancer patients. TNBCs constitute 12–17% of all breast cancer subtypes, affecting younger women more frequently than patients in other age groups (Almansour, 2022). Histologically, TNBCs are characterized by less than 1% cellular expression of progesterone and estrogen receptors and 0 and 1+ expression of human growth factor receptor 2. Clinically, TNBC tumors are

associated with later stage at diagnosis, increased mortality, recurrence, metastatic patterns, and poor prognosis (Dent et al, 2007).-negative breast cancer (TNBC) is an aggressive breast cancer. It spreads quickly and has few treatment options. It is also serious because of its rate of recurrence. Women of color are twice as likely as white women to be diagnosed with TNBC. They are also more likely to die from this devastating disease. In fact, the five-year survival rate for TNBC in women of color is only 14% compared to 36% in women from other racial backgrounds. Multiple biological and socioeconomic factors are blamed for this higher risk.

Researchers from the Bhatnagar Laboratory at the UC Davis Comprehensive Cancer Center have been working to get to the bottom of the genetic determinants of the racial disparity in TNBC. Results from their research were recently published in EMBO Reports. The Bhatnagar Laboratory has been studying a protein called TRIM37 for over 10 years after Professor Bhatnagar discovered its role as a breast cancer-causing gene. The protein, called TRIM37 in reference to the gene, is present in high numbers in breast cancer tissues. It is associated with poor patient survival.

TRIM37 is a driver of triple-negative breast cancer (TNBC) spread and resistance to chemotherapy. Professor Bhatnagar and her research team have persevered in studying TRIM37 to find out why it may hold the key to Women of Color getting and dying of TNBC at high rates. The hope of the study is that it”s findings could

help develop TRIM37 as a predictive biomarker, which eventually could improve TNBC diagnosis, individualized risk evaluation, and prognosis for every single Woman of Color concerned.

Unraveling the mystery

The research team discovered that the TRIM37 variant known as rs57141087 is predominant in Women of Color and modulates TRIM37 levels through enhancer-promoter interactions, Specifically, TRIM37 overexpression in early stages of triple-negative breast cancer (TNBC)promotes neoplastic transformations (formation of tumor), accelerates tumorigenesis (tumor growth) and drives cells into malignancy (spread of cancer).

Essentially, if a patient has tumors with high levels of TRIM37 protein, it indicates poor prognosis and overall survival and an increased likelihood of metastasis. Increased early-stage TRIM37 levels appear to give cancer cells a “head start,” impacting the disease trajectory and outcomes.

In this latest research, Bhatnagar’s lab showed that the cancer-free breast tissue from Women of Color expresses a relatively high level of this protein, which predisposes them to aggressive disease. The t variant might be the reason why.

Methodology

The research team used comprehensive genomic and functional analysis to uncover the genetic drivers that predispose Women of Color to aggressive TNBC. The analysis identified the ancestry-specific, genomic feature at a single base position in DNA called rs57141087. Information from a total of 319 patients was included. Interestingly, the meta-analysis revealed ~1.63-fold higher TRIM37 expression in early histological Stage I TNBC tumors from Women of Color than in white women, which was not the case for Stage II–IV. The team’s analysis confirmed the association between TRIM37 expression in the Stage I TNBC tumors with racial identity. Next, the researchers assessed to what extent the early-stage differences in TRIM37 expression could explain the disparity in the overall survival of TNBC patients.

The findings showed Women of Color with TNBC tumors expressing high TRIM37 showed poor overall survival, with a median survival of ~114 months (9.5 years) as compared to white women, with a median survival of ~245 months (20.4 years). Notably, no significant differences in overall survival were observed for low TRIM37-expressing TNBC tumors from Women of Color and white women.

The team has previously engineered a novel TRIM37 targeting approach. They used TRIM37-specific, synthetic RNA-based inhibitor delivered in vivo by small vesicles, called nanoparticles. A patent for targeting TRIM37 using nanoparticle delivery mechanisms is pending.

The teams work provided pre-clinical proof-of-concept regarding TRIM37 as a clinically relevant target for TNBC treatment. The hope is that further research can be done to test TRIM37 as a therapeutic target for slowing down TNBC and develop TRIM37 as a predictive biomarker for TNBC in Women of Color. Such concepts may also rise hope for early recognition and early therapy options for the many Women of Color in Africa, where particularly in West Africa the prevalence of TNBC is excessively high. Prevalences might be high in other, not yet investigated ethnicities; further research is thus warranted.

Thasso had already a couple of articles on divers constellations and aspects around breast cancer, including some genetic aspects here, here, here, and here.

See here also a sequence on breast cancer in Women of Color:

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