Biomarker Predictors for Immunotherapy Benefit in Breast: Beyond PD-L1

  • Jamaal L. James
  • Justin M. BalkoEmail author
Immuno-oncology (S Tolaney, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Immuno-oncology


Purpose of Review

Immune checkpoint blockade (ICB) has changed the clinical course of multiple cancer types and durable responses have now been observed in breast cancer (BC) patients. Most data suggest that, compared to other subtypes, triple-negative BC (TNBC) patients are more responsive to ICB, and anti-PD-L1 therapy is now approved in PD-L1+ metastatic TNBC, in combination with chemotherapy.

Recent Findings

Nearly 40% of PD-L1+ TNBC patients did not respond to this combination. Thus, additional biomarkers appear to be necessary to more precisely identify potential responders. A comprehensive analysis of the breast tumor microenvironment (TME) and peripheral blood may identify potential biomarkers for a more accurate selection of patients likely to respond to ICB.


Herein, we summarize key features of the breast TME, and beyond, that may hold predictive power in determining immunotherapy benefit. Incorporation of these features in controlled clinical trials may help further guide personalized care for BC immunotherapy.


Breast cancer Biomarkers Programmed death-ligand 1 


Compliance with Ethics Standards

Conflict of Interest

Justin Balko reports research support from Genentech/Roche, Bristol Myers Squibb, and Incyte Corporation; has received consulting/expert witness fees from Novartis; is an inventor on provisional patents regarding immunotherapy targets and biomarkers in cancer; and has a patent 15/376,276 pending on the use of MHC-I/II to predict response to immunotherapy. Jamaal James declares no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  2. 2.Cancer Biology ProgramVanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of Pathology, Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleUSA
  4. 4.Breast Cancer Research ProgramVanderbilt University Medical CenterNashvilleUSA

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