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Triple-negative breast cancer patients treated with immune checkpoint inhibitors may experience a greater antitumoral immune response, according to a recent literature review.

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized solid tumor malignancy treatment. ICIs target immunosuppressive receptors such as programmed cell death ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The best breast cancer ICI evidence is for triple-negative breast cancer (TNBC). 

A study published in the journal JCO Oncology Practice reviewed the role of immunotherapy in breast cancer.

Monotherapy in Metastatic TNBC

Initially, the safety and efficacy of immunotherapy were tested in patients with metastatic TNBC (mTNBC). The KEYNOTE-012 and KEYNOTE-086 studies showed that pembrolizumab monotherapy worked better as a first-line treatment for PD-L1-positive (PD-L1+) patients. In the KEYNOTE-355 study, pembrolizumab plus chemotherapy improved progression-free and overall survival in metastatic TNBC patients with a PD-L1 combined positive score ≥ 10.

Immunotherapy With Chemotherapy for Advanced TNBC

Many phase III trials have examined ICIs and chemotherapies in first-line, locally metastatic TNBC patients. Thus, atezolizumab with nabpaclitaxel for mTNBC initially received expedited United States regulatory clearance and complete global approval. However, approval was subsequently withdrawn for atezolizumab with nab-paclitaxel for patients with PD-L1+ mTNBC on the basis of a lack of confirmatory positive results, though the combination remains approved in many countries. 

Use of Antibody–Drug Conjugates

When people with early-stage cancer were given neoadjuvant ICI along with standard chemotherapy, the rate of pathologic complete response (pCR) at surgery went up. In the large KEYNOTE-522 research, neoadjuvant and adjuvant ICI enhanced event-free survival.

Biomarkers Predictive of ICI Response

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ICI response biomarkers are still being studied. A rise in pCR in both KEYNOTE-522 and IMpassion31 phase III studies was observed for early-stage TNBC regardless of PD-L1 status, although PD-L1 positivity predicted higher rates. Other biomarkers, like PD-1/PD-L1 expression, tumor mutational load, tumor-infiltrating lymphocytes, and multigene tests collecting favorable immune cell signatures, may predict ICI treatment efficacy.

Future Directions of Immunotherapy 

TNBC treatment with CTLA-4 and PD-L1 suppression is gaining interest. The Phase II DART research examined ipilimumab (a CTLA-4 inhibitor) with nivolumab (a PD-1 inhibitor) in metaplastic breast cancer patients who had received several therapies. Lymphocyte activation gene 3 is another immune checkpoint target being explored. Early-phase trials are examining PVX-410 and other cancer vaccines.

Source:
Jacob, S., Huppert, L. A., & Rugo, H. S. (2023). Role of immunotherapy in breast cancer. JCO Oncology Practice, 19(4), 167–179. https://doi.org/10.1200/op.22.00483