Biomarkers for breast cancer immunotherapy: PD-L1, TILs, and beyond

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) have recently entered into the therapeutic scenario of metastatic breast cancer. However, only a proportion of patients benefit from ICIs and immune-based combinations, so the identification of reliable predictors of response remains an unmet need.

Areas covered

We discuss potential predictors of response to ICIs in breast cancer, including PD-L1 expression, tumor-infiltrating lymphocytes (TILs), tumor mutational burden (TMB), and several other biomarkers and suggest future directions of research in this setting. A literature search was conducted in October 2021 of Pubmed/Medline, Cochrane library and Scopus databases; in addition, abstract of international cancer meetings were reviewed.

Expert opinion

In terms of predictors of response to immunotherapy in TNBC patients, several biomarkers are being evaluated. Valuable data on predictive biomarkers have recently emerged, including host-related factors, immune-related cells, and protein and genetic markers. Data supporting immunotherapy in the metastatic triple-negative breast cancer setting are not concordant, but there have been some positive phase III trials including IMpassion130 and KEYNOTE-355. Phase II and III (neo)adjuvant trials are supportive of this therapeutic strategy. Further investigations are warranted in this challenging area.

KEYWORDS:

• Breast cancer
• triple negative breast cancer
• PD-L1
• predictive biomarkers
• immune checkpoint inhibitors
• TILs

Article Highlights

• Following the advent of immune checkpoint inhibitors (ICIs), immunotherapy has recently entered into breast cancer clinical practice.

• A great understanding of mechanisms of primary and adaptive resistance to ICIs is an unmet need.

• The development of robust predictive biomarkers for optimal patient selection is key in a setting where a proportion of patients do not respond to immunotherapy

• PD-L1 is currently considered the most important predictive biomarker since chemoimmunotherapy has been suggested to be effective in PD-L1 positive patients, according to landmark clinical trials in this setting.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.