Genetic and Metabolic Differences May Drive More Aggressive Breast Cancer in Latin American Women: William Audeh, MD, MS

Aggressive early-stage breast cancer is more often diagnosed in Latin American women compared with non-Hispanic White women.¹ A poster at the 2025 annual San Antonio Breast Cancer Symposium highlighted the genetic differences between Latin American women, Black women, and non-Hispanic White women, underscoring disparities in breast cancer research.

The poster, presented by William Audeh, MD, MS, chief medical officer of Agendia, cited results from the MammaPrint, BluePrint, and Full-genome Data Linked With Clinical Data to Evaluate New Gene EXpression Profiles (FLEX; NCT03053193) clinical trial. In an interview with The American Journal of Managed Care^®, Audeh said these findings provide actionable insights for directing patient care for those with breast cancer.

Transcript

This transcript has been lightly edited. Captions are auto-generated.

What do your findings reveal about the unique tumor biology in Latin American patients with obesity and early breast cancer, and how might they influence clinical decision-making?

Our presentation was really intended to try to understand how genetic ancestry, as identified by self-reported race or ethnicity, and obesity and how these two factors may affect the biology of newly diagnosed breast cancer. Our goal, based upon our FLEX study, which had enrolled nearly 1500 women of Latin American descent, was to make comparisons between Latin American women, self-reported Black women, and non-Hispanic White women to see if there were important differences that affected the nature of the breast cancer that had developed in those women.

What we observed was that there actually were differences, particularly focusing on the Latin American women. Of course, we noticed in the clinical features that there was more obesity in the Latin American women and Black women compared to non-Hispanic White women, as well as more type 2 diabetes, something that you might expect to go along with obesity. We know that that factor actually adds some inflammation to the system, which can be promoting of more aggressive breast cancers.

Importantly, we found that in Latin American women, particularly those with obesity, their breast cancers appeared to have metabolic differences that distinguish them from Black women and White women, more evidence of inflammation and changes in the metabolism, which suggests there may be some specific therapies, such as immunotherapy, that may be especially effective in women with breast cancer who are of Latin descent.

How should clinicians interpret these divergent metabolic and immune signatures when assessing prognosis or treatment strategies?

[With] these sorts of studies, we're using the power of the FLEX study, which has collected whole transcriptome data on every woman who's enrolled in this study. We now have nearly 22,000 women with early-stage breast cancer enrolled in this study. 10% of them are of Latin descent, and a little over 10% are of self-reported Black ancestry. We're really focused on not only having a large number of women with early-stage breast cancer but also representing diverse populations to try to understand what may be different about them.

Our findings in this particular study are encouraging in that they appear to suggest that immunotherapy, which is moving into breast cancer, may be especially effective in Latin women with breast cancer, either triple-negative breast cancer or possibly hormone-positive breast cancer. The metabolic aspects we are still evaluating, but there are clearly differences in the way that these breast cancers have developed and how they are affected by obesity. This is an area that we will continue to study.

Why is it important to move beyond traditional clinical variables and incorporate transcriptomic profiling when evaluating disparities in breast cancer?

Our understanding of breast cancer, of course, always starts with basic standard pathology: the way the cancer looks under the microscope and what type of cancer it is based upon the stains that pathologists use, [eg] hormone-positive, HER2-positive, or triple negative. These are the basic categories of breast cancer, but we can only go so far in understanding the real biology and nature of breast cancer in terms of predicting how it will respond to therapy and which therapies are best.

To get beyond what the microscope tells us, we really need to go down to the level of the genome, and it's actually in the genes of the cancer where the real problem lies. And that is why we are committed to this study, which captures the whole transcriptome data for every gene. A gene that is active or inactive really tells us much more about the nature of breast cancer, because our goal is to achieve a cure for every woman diagnosed with breast cancer, but we want to do that with as little toxicity as possible. And in order to do that, we have to be as precise as we can with designing the appropriate therapy. And I think it's this genomic information that's really allowing us to do that.

References

1. Mazo Canola M, Santillan A, Alberty-Oller JJ, et al. Distinct immune and metabolic profiles in Latin American breast cancer patients with obesity enrolled in FLEX. Poster presented at: San Antonio Breast Cancer Symposium (SABCS) 2025; December 11, 2025; San Antonio, TX. Poster PS4-09-0