Genomic Tools Highlight Genetic Differences Linked to More Aggressive Breast Cancer in Latin Women: William Audeh, MD, MS

Genetic differences increasing the risk of early-stage aggressive breast cancer in Latin American women with obesity underscored research disparities, according to a poster presented at the 2025 San Antonio Breast Cancer Symposium.1

The poster presented by William Audeh, MD, MS, chief medical officer at Agendia and board-certified internal medicine oncology specialist, highlighted findings from the MammaPrint, BluePrint, and Full-genome Data Linked With Clinical Data to Evaluate New Gene EXpression Profiles (FLEX; NCT03053193) clinical trial. The trial included 15,577 patients whose entire transcriptome data revealed a higher prevalence of obesity and type 2 diabetes among the Latin American women in the study compared with Black and non-Hispanic White women.1

The genomic tools used in the study included MammaPrint, a standard-of-care 70-gene assay, whereas BluePrint is an 80-gene assay used to guide anthracycline chemotherapy in patients with hormone receptor-positive and HER2-negative early breast cancer. When used together, they provide insights that can optimize treatment decisions for patients.2

“[These tools help us to see] what is driving the growth of that breast cancer, and that can help select therapies, and if you're going to use chemotherapy, which chemotherapy drug may have the better effect,” Audeh said in an interview with The American Journal of Managed Care®.

This transcript was lightly edited; captions were auto-generated.

Transcript

How do the MammaPrint, BluePrint, and ImPrint together create a more precise understanding of early breast cancer biology across diverse populations?

MamaPrint, as you may know, is a standard-of-care 70-gene assay that predicts the risk of recurrence and can be used to answer many questions for a newly diagnosed breast cancer patient. Not only does she need chemotherapy, but also, whether therapy should be given before surgery or after. It also provides guidance for managing the endocrine therapy component of treatment for hormone-positive breast cancers. MammaPrint answers many questions that are part of the standard-of-care decision-making. Blueprint is 80 genes that look at a different aspect of breast cancer biology. It's what is driving the growth of that breast cancer, and that can help select therapies; if you're going to use chemotherapy, which chemotherapy drug may have a better effect? We can predict, for example, whether anthracycline or adriamycin, one of the more toxic chemotherapy drugs, might actually be helpful in particular cases.

ImPrint is still an experimental signature, but we're able to use it in our FLEX database, and that identifies tumors that have immune activation, where the immune system appears to be more active but hasn't yet been able to eradicate the cancer. These are cancers that we know from other studies, if they are ImPrint-positive, as we say, they will particularly respond well to immunotherapy.

What we observed in the Latin American patients was a higher rate of having ImPrint-positive breast cancers, which really does predict that there will be a benefit of immunotherapy for these women. But we also did notice, not surprisingly, that the frequency of higher-risk breast cancers, according to the MammaPrint risk, was more common in Latin women and Black women compared to non-Hispanic White women. This is something we've observed previously, but not very often in such a large number of Latin women with breast cancer, where we did see that they had more high-risk breast cancers than the other ethnicities.

Could these insights inform future therapeutic approaches, including endocrine therapy choices or immunotherapy responsiveness?

Yes, absolutely. I think that's where this is pointing to. Obesity adds a level of inflammation and immune system involvement that does tend to lead to a more aggressive type of breast cancer, which may more often need chemotherapy, for example. We now find, at least from studies like this, the suggestion that these cancers in women with obesity, as well as Latin ancestry, may have better responsiveness to immunotherapy.

The metabolic aspect is also important because we know that with obesity, there's a higher rate of type 2 diabetes, which changes the way cancer cells metabolize glucose and other nutrients. This is an area that can also be addressed with other therapies that we have for breast cancer, such as mTOR inhibitors, things that work more in the realm of the metabolism of breast cancer.

What steps should clinicians take to ensure genomic tools and treatment guidelines support better outcomes for underrepresented populations?

Most of the genomic data that we have in breast cancer has not fully represented women of color and women of different genetic ancestry. We are limited by the way we can measure that based upon what a woman describes herself to be—whether she describes herself as Black, Latin, or White. But based upon that way of indicating genetic ancestry, we have been very focused in our FLEX study on enrolling as diverse a population as we can to try to remedy this lack of data in women of color.

We have over 100 sites around North America that have this study open. As I mentioned, we have nearly 22,000 women in this study. And we're approaching, as of our last count, nearly 2000 women of Black ancestry or Latin ancestry. This will soon become one of the largest databases that represents women of color in a way that other genetic studies really haven't done before.

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; December 9-12, 2025; San Antonio, TX. Poster PS4-09-0

2. Agendia to showcase Mammaprint and blueprint utility in guiding anthracycline therapy at the 2025 San Antonio Breast Cancer Symposium. Agendia. November 25, 2025. Accessed January 5, 2026. https://agendia.com/agendia-to-showcase-mammaprint-and-blueprint-utility-in-guiding-anthracycline-therapy-at-the-2025-san-antonio-breast-cancer-symposium/