From Cold to Hot: Navigating a New Frontier of Breast Cancer Immunotherapy

Sarah Poland, MD, lead author of a recently published article in the journal ONCOLOGY titled Advances in Immunotherapy for Breast Cancer, highlighted key findings from her review in a conversation with CancerNetwork®.¹ Throughout the discussion, she spoke about:

Shifting Perspectives on Immunogenicity: Historically, breast cancer was considered a “cold,” poorly immunogenic tumor due to low tumor mutational burden (TMB) and few tumor-infiltrating lymphocytes (TILs). Poland highlighted how clinical research has shifted this perspective, particularly through the study of triple-negative breast cancer (TNBC), which often exhibits higher PD-L1 expression and immune infiltration.

Key Clinical Milestones: The review highlighted foundational data that established immunotherapy as a standard of care:

• Early-Stage TNBC: The phase 3 KEYNOTE-522 trial (NCT03036488) established pembrolizumab (Keytruda) plus chemotherapy as a standard neoadjuvant treatment for stage II to III TNBC.²
• Metastatic TNBC: The phase 3 KEYNOTE-355 trial (NCT02819518) demonstrated the benefit of pembrolizumab in PD-L1–positive metastatic disease.³

Managing Toxicity and Rechallenge: Poland addressed the feasibility of pembrolizumab rechallenge after an immune-related adverse effect (irAE), emphasizing that while possible, it requires a highly individualized approach based on the severity and timing of the initial toxicity.

The Future Landscape: Beyond PD-1/PD-L1 inhibitors, the discussion covered emerging technologies that are poised to redefine treatment:

• Antibody-Drug Conjugates (ADCs): Exploration of novel combinations of ADCs with immunotherapy.
• Emerging Modalities: The potential role of bispecific antibodies and vaccine trials utilizing tumor antigens.
• Subtype Expansion: Emerging evidence supporting the efficacy of immunotherapy in hormone receptor–positive and HER2-positive subtypes, moving beyond the traditional focus on TNBC.

Unmet Educational Needs: Poland emphasized the importance of resources that connect providers and patients, particularly in translating complex trial data into clinical practice and addressing patient concerns regarding the newest therapies and trials.

Poland is from the Department of Medicine in the Section of Hematology/Oncology at The University of Chicago.

References

1. Poland S, de Oliveira Andrade M, Nanda R. Advances in immunotherapy for breast cancer. Oncology (Williston Park). 2026;40(1):8-15. doi:10.46883/2026.25921061
2. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549
3. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809