Current Landscape of Immunotherapy in Breast Cancer: A Review

Abstract

Importance: There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing at the time of this narrative review. The objective of this review is to describe the current status of immunotherapy in breast cancer, highlighting its potential in both early-stage and metastatic disease.

Observations: After searching ClinicalTrials.gov on April 24, 2018, and PubMed up to June 30, 2018, to identify breast cancer immunotherapy trials, we found that immune checkpoint blockade (ICB) is the most investigated form of immunotherapy in breast cancer. Use of ICB as monotherapy has achieved objective responses in patients with breast cancer, with higher rates seen when administered in earlier lines of therapy. For responding patients, those responses are durable. More recent data suggest clinical efficacy when ICB is given in combination with chemotherapy. Ongoing studies are evaluating combination strategies pairing ICB with additional chemotherapeutic agents, targeted therapy, vaccines, and local ablative therapies to enhance response. To date, robust predictive biomarkers for response to ICB have not been established.

Conclusions and relevance: It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions. Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors.

Figure 1.. Breast Cancer Immunotherapy Trials by Type of Immunotherapeutic Agent or Strategy Being Investigated and by Study Phase

As of April 24, 2018, review of ClinicalTrials.gov identified 293 actively accruing trials evaluating immunotherapeutic agents in breast cancer. “Other” includes natural killer cell therapy, transarterial chemoembolization, and first-in-class agents.

Figure 2.. Breast Cancer Immunotherapy Trials

A, Trials by specific subtype of breast cancer being studied. B, Trials investigating immune checkpoint blockade agents alone or in various combinations. “Targeted therapy” includes ERBB2-targeting agents (trastuzumab, pertuzumab, T-DM1), CSFIR inhibitors, HDAC inhibitors, PARP inhibitors, pan-CDK inhibitors, P13K inhibitors, JAK2 inhibitors, adenosine A2 receptor inhibitors, AKT inhibitors, and tyrosine kinase inhibitors. “Other” includes novel monoclonal antibodies (eg, OX40, GITR), first-in-class molecules, as well as combinations with more than 2 active agents (eg, checkpoint inhibitors, vaccines, chemotherapy, irradiation, endocrine therapy, cytokines) in adaptive clinical trials. CDK indicates cyclin-dependent kinase; DCIS, ductal carcinoma in situ; HR, hormone receptor; IBC, inflammatory breast cancer; TNBC, triple-negative breast cancer.