Dataset Information

The emerging role of immune checkpoint inhibitors for the treatment of breast cancer.

ABSTRACT:

Introduction

Breast cancer has traditionally been viewed as immunogenically 'cold,' but two immune checkpoint inhibitors have been approved in combination with chemotherapy for PD-L1 positive advanced triple-negative breast cancer (TNBC), and pembrolizumab was also recently approved for early stage TNBC. As the landscape is rapidly evolving, a comprehensive review of checkpoint inhibitors in breast cancer is needed to aid clinicians in selecting appropriate candidates for therapy, and to highlight ongoing promising studies in this area and topics in need of further investigation.

Area covered

This review summarizes the latest evidence from completed and ongoing trials of immune checkpoint inhibitors. Ongoing studies were identified using a search of ClinicalTrials.gov with the term 'breast cancer' along with specific checkpoint inhibitor agents.

Expert opinion

A number of novel combination strategies are under investigation to enhance response and overcome resistance to immunotherapy, with promising preliminary data from checkpoint inhibitors targeting TIGIT, combinations with small molecule inhibitors such as lenvatinib, and injectable agents directly influencing the immune microenvironment. As immunotherapy enters into the curative setting, biomarkers predictive of immunotherapy benefit are needed, as PD-L1 status has not been a helpful discriminator in completed trials in early-stage breast cancer.

SUBMITTER: Howard FM

PROVIDER: S-EPMC8995399 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The emerging role of immune checkpoint inhibitors for the treatment of breast cancer.

Howard Frederick M FM Villamar Dario D He Gong G Pearson Alexander T AT Nanda Rita R

Expert opinion on investigational drugs 20211011 6

<h4>Introduction</h4>Breast cancer has traditionally been viewed as immunogenically 'cold,' but two immune checkpoint inhibitors have been approved in combination with chemotherapy for PD-L1 positive advanced triple-negative breast cancer (TNBC), and pembrolizumab was also recently approved for early stage TNBC. As the landscape is rapidly evolving, a comprehensive review of checkpoint inhibitors in breast cancer is needed to aid clinicians in selecting appropriate candidates for therapy, and to ...[more]

PMID: 34569400

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Project description:UnlabelledTraditional treatment modalities for advanced cancer (radiotherapy, chemotherapy, or targeted agents) act directly on tumors to inhibit or destroy them. Along with surgery, these modalities are predominantly palliative, with toxicity and only modest improvements in survival in patients with advanced solid tumors. Accordingly, long-term survival rates for most patients with advanced cancer remain low, thus there is a need for cancer treatments with favorable benefit and toxicity profiles that can potentially result in long-term survival. The immune system plays a critical role in the recognition and eradication of tumor cells ("immune surveillance"), and immunotherapies based on this concept have been used for decades with some success against a few tumor types; however, most immunotherapies were limited by a lack of either substantial efficacy or specificity, resulting in toxicity. We now have a greater understanding of the complex interactions between the immune system and tumors and have identified key molecules that govern these interactions. This information has revitalized the interest in immunotherapy as an evolving treatment modality using immunotherapeutics designed to overcome the mechanisms exploited by tumors to evade immune destruction. Immunotherapies have potentially complementary mechanisms of action that may allow them to be combined with other immunotherapeutics, chemotherapy, targeted therapy, or other traditional therapies. This review discusses the concepts and data behind immunotherapies, with a focus on the checkpoint inhibitors and their responses, toxicities, and potential for long-term survival, and explores promising single-agent and combination therapies in development.Implications for practiceImmunotherapy is an evolving treatment approach based on the role of the immune system in eradicating cancer. An example of an immunotherapeutic is ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses. Ipilimumab is approved for advanced melanoma and induced long-term survival in a proportion of patients. The programmed death-1 (PD-1) checkpoint inhibitors are promising immunotherapies with demonstrated sustained antitumor responses in several tumors. Because they harness the patient's own immune system, immunotherapies have the potential to be a powerful weapon against cancer.

Project description:Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient's own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.

Dataset Information

The emerging role of immune checkpoint inhibitors for the treatment of breast cancer.

Introduction

Area covered

Expert opinion

Publications

The emerging role of immune checkpoint inhibitors for the treatment of breast cancer.

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