New Immunogenomic Findings Offer Deeper Biological Insight into TNBC

Triple-negative breast cancer (TNBC), a subtype defined by the absence of estrogen receptor, progesterone receptor, and HER2 expression, continues to pose major therapeutic challenges due to its heterogeneity and aggressive clinical behavior.¹

Unlike other breast cancer subtypes, TNBC does not have any established molecular targets, so chemotherapy and a few targeted agents are the primary treatment options. There is an increasing amount of evidence that TNBC should not be considered as one single entity but rather as a biologically different disease at the molecular and immunologic levels with distinct subgroups, each of them having potential therapeutic implications.^1,2

A Large Multi-Institutional Study Reveals New Tumor Subgroups

A significant step explaining the biological variations of TNBC comes from a large-scale study emphasized by News-Medical, which examined the tumors of more than 250 Black and White women to identify the immunogenomic patterns influencing the behavior of the disease.² The study published in npj Breast Cancer revealed that neither racial background nor obesity, when considered separately, were factors that could predict clinical outcomes, which is a very significant change of direction compared to the assumption of the past.³ What features of the tumor, therefore, really matter? The biology of the tumors, their gene-expression signatures, and the amount of immune infiltration, were the main factors determining the patients' survival.³

Among the significant discoveries was the identification of a previously unrecognized TNBC subgroup with "stem-cell-like and luminal-like" present in both Black and White patients.³ This subgroup revealed the mixture of the hormonal-like signaling pathways and the stem-cell–associated gene expression that led to the hypothesis that some TNBC tumors may be sensitive to new or existing therapies in a way that is quite different from what has been anticipated.

Researchers also reported substantial differences in immune cell infiltration among tumors, noting that tumors from Black women showed higher levels of specific immune cell subsets.³ These findings may help explain why some TNBC cases respond well to immunotherapy while others do not. As summarized in the News-Medical report, the discovery “provides a major step toward developing more personalized and effective treatments for women with TNBC”.²

Why Immunogenomic Diversity Matters for Treatment Development

The research emphasizes that TNBC should not be considered a single entity based solely on receptor status. Instead, underlying immunologic and genomic factors may more accurately predict treatment response and progression. Previous literature has already categorized TNBC into several transcriptional subtypes—such as basal-like, mesenchymal, immune-enriched, and luminal androgen receptor types—each with distinct biology and potential therapeutic vulnerabilities.⁴ The current data help to clarify these differences even further by providing the information that there are immune variations related to ancestry and that there are also some newly identified hybrids for which the signature is not clear.

With these immunogenomic insights, the path to more personalized strategies becomes clear for both clinical practice and drug development. Immune checkpoint inhibitors may be most effective for tumors with high levels of immune infiltration. In contrast, tumors with luminal-like characteristics may, in the future, be treated with hormonal or differentiation-based therapies that are generally excluded for TNBC.

Repurposed Drugs May Provide Additional Benefit

Emerging research continues to explore adjunctive therapies that may improve outcomes for TNBC patients. A Pharmacy Times report highlighted a study showing that statin and metformin use was associated with improved survival in early-stage TNBC.⁵ “The use of statins and metformin was independently associated with improved survival in patients with early-stage triple-negative breast cancer (TNBC), according to data to be presented at the European Society for Medical Oncology Congress 2025 in Berlin, Germany.”⁵

Although retrospective, these findings align with the broader shift toward examining metabolic, inflammatory, and immunologic pathways as therapeutic targets—many of which intersect with the immunogenomic profiles identified in the recent TNBC study.

Implications for Pharmacists and Clinical Teams

As TNBC research evolves, pharmacists play an increasingly important role in interpreting emerging biomarker-driven strategies, supporting patient education, and helping integrate treatment approaches that include immunotherapy, targeted therapy, and repurposed medications. Knowledge of the different biologic aspects of TNBC enables pharmacists to forecast adverse effects, assess the right candidates for new agents, and support participation in precision-medicine clinical trials.

Conclusion

The recent immunogenomic study brings much-needed clarity to the complex biological landscape of TNBC. By identifying new tumor subgroups and clarifying the influence of ancestry-linked immune patterns, the research pushes the field closer toward personalized treatment strategies. Combined with complementary findings—such as potential benefits from repurposed therapies like statins and metformin—the landscape of TNBC management is gradually shifting from generalized approaches toward more biologically informed precision care.

REFERENCES

1. Merck & Co., Inc. From Awareness to Action: Understanding Triple-Negative Breast Cancer (TNBC). Merck.com. Published September 29, 2025. Accessed November 25, 2025. https://www.merck.com/stories/from-awareness-to-action-understanding-triple-negative-breast-cancer-tnbc/

2. News-Medical. Study reveals biological insights into triple negative breast cancer. News-Medical.net. Published November 24, 2025. Accessed November 25, 2025. https://www.news-medical.net/news/20251124/Study-reveals-biological-insights-into-triple-negative-breast-cancer.aspx

3. Hossain F, Senapati S, Olsen A, et al. Immunogenomic diversity of triple-negative breast cancers in obese and non-obese Black and White women. npj Breast Cancer. 2025;11(1). doi:10.1038/s41523-025-00836-6

4. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750-2767. doi:10.1172/JCI45014

5. Gerlach A. Statins and metformin improved survival in patients with triple-negative breast cancer. Pharmacy Times. Published October 15, 2025. Accessed November 25, 2025. https://www.pharmacytimes.com/view/statins-and-metformin-improved-survival-in-patients-with-triple-negative-breast-cancer