How has Immunotherapy Evolved in Breast Cancer Treatment?

Historically, breast cancer was categorized as a "cold" malignancy—characterized by a low tumor mutational burden and a sparse immune microenvironment that offered little hope for early immunotherapy interventions. However, the treatment landscape has undergone a dramatic transformation, particularly for patients with triple-negative breast cancer (TNBC) who previously lacked targeted therapeutic options.

In this interview, Sarah Poland, MD, co-author of the recent review "Advances in Immunotherapy for Breast Cancer," published in ONCOLOGY, explored the clinical turning points that redefined our understanding of breast cancer immunogenicity.¹ Poland, a fellow at The University of Chicago, discussed how early phase 1 data from the KEYNOTE-012 study (NCT01848834) challenged the status quo, proving that PD-1 blockade could elicit durable responses in PD-L1–positive tumors and laying the essential groundwork for the current standard of care in breast oncology.²

Transcript:

When immunotherapy was initially being studied, breast cancer was not one of the most exciting types of cancer that they were looking at to treat with this type of new therapy. There are multiple reasons for that. In prior studies or prior research, particularly in the lab, breast cancer wasn’t one of the types of cancer that seemed the most immunologically active that seemed like it had the highest tumor mutational burden, or an immune microenvironment around the tumor that seemed to have a high proportion of tumor infiltrating lymphocytes, or things that would lend it to being a good candidate for immunotherapy. When we saw other malignancies being treated with immunotherapy, such as melanoma, which has traditionally been difficult to treat, especially in the metastatic setting, there became a lot of excitement for all different types of cancers in oncology.

Particularly for triple negative breast cancer, given the lack of targetable mutations, for example, hormone receptor-positive breast cancer, we’re able to target the estrogen receptor for HER2-positive breast cancer, [and] we’re able to target the HER2 receptor. For triple negative breast cancer, for a long time, we didn’t have a lot of answers beyond traditional chemotherapy, and so there was a lot of interest in utilizing this subtype, particularly as a potential option for immunotherapy. As we mentioned in the review, the phase 1 KEYNOTE-012 study was the first study to evaluate pembrolizumab [Keytruda] monotherapy.

Pembrolizumab is a PD-1 blocking antibody and a type of immunotherapy in PD-L1–positive tumors. The fact that there was an 18.5% overall response rate, as well as multiple patients noted in the study that had some long-lasting responses to pembrolizumab, this was a turning point for us that changed opinion on if this could be possible to treat breast cancer in this way, and laid the foundation for a lot of our immunotherapy trials that we go on to discuss further in the review.

References

1. Poland S, de Oliveira Andrade Md M, Nanda R. Advances in immunotherapy for breast cancer. Oncology (Williston Park). 2026;40(1):8-15. doi:10.46883/2026.25921061
2. Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016;34(21):2460-2467. doi:10.1200/JCO.2015.64.8931