Immunotherapy in Breast Cancer: When, How, and What Challenges?

Henriques, Beatriz Carvalho; Mendes, Fernando; Martins, Diana

doi:10.3390/biomedicines9111687

Cited by 44 publications

(39 citation statements)

References 114 publications

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“…Because the immune system has already recognized this cancer, the pre-existing response can be improved with immunotherapies, enhancing breast cancer immunogenicity. Breast cancer is less immunogenic than other tumor forms; nonetheless, anti-PD1/PD-L1 drugs have been studied in breast cancer in recent years, specifically in the triple-negative subtype, with promising results when used alone or in combination with other treatments [ 10 ]. Immune cells play an essential role in breast cancer recognition and early eradication and tumor progression.…”

Section: Breast Cancer Therapeutic Optionsmentioning

confidence: 99%

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Drug Metabolism for the Identification of Clinical Biomarkers in Breast Cancer

Costa

Vale

2022

IJMS

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Breast cancer is classified into four major molecular subtypes, and is considered a heterogenous disease. The risk profiles and treatment of breast cancer differ according to these subtypes. Early detection dramatically improves the prospects of successful treatment, resulting in a reduction in overall mortality rates. However, almost 30% of women primarily diagnosed with the early-stage disease will eventually develop metastasis or resistance to chemotherapies. Immunotherapies are among the most promising cancer treatment options; however, long-term clinical benefit has only been observed in a small subset of responding patients. The current strategies for diagnosis and treatment rely heavily on histopathological examination and molecular diagnosis, disregarding the tumor microenvironment and microbiome involving cancer cells. In this review, we aim to praise the use of pharmacogenomics and pharmacomicrobiomics as a strategy to identify potential biomarkers for guiding and monitoring therapy in real-time. The finding of these biomarkers can be performed by studying the metabolism of drugs, more specifically, immunometabolism, and its relationship with the microbiome, without neglecting the information provided by genetics. A larger understanding of cancer biology has the potential to improve patient care, enable clinical decisions, and deliver personalized medicine.

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Section: Breast Cancer Therapeutic Optionsmentioning

confidence: 99%

“…Therefore, some mAb have been used as therapeutic agents, with Trastuzumab as an example of passive immunotherapy [ 11 ]. In recent years, additional modalities, such as antibody-drug conjugates (ADC) and ICIs, have been studied as a prophylactic and treatment approach for breast cancer [ 10 ].…”

Section: Breast Cancer Therapeutic Optionsmentioning

confidence: 99%

Drug Metabolism for the Identification of Clinical Biomarkers in Breast Cancer

Costa

Vale

2022

IJMS

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“…However, cancer cells often develop mechanisms of immune escape that limit the ability of innate and adaptive immunity responses. These mechanisms truly predetermine both cancer progression and the response of patients to cancer immunotherapy protocols [ 20 , 21 , 22 ]. Therefore, a better understanding of these mechanisms may open the door to innovative and more efficient therapies for cancer.…”

Section: Mechanisms Of Cancer Immune Escapementioning

confidence: 99%

Nanomedicine as a Promising Tool to Overcome Immune Escape in Breast Cancer

et al. 2022

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Breast cancer is the most common type of malignancy and leading cause of cancer death among women worldwide. Despite the current revolutionary advances in the field of cancer immunotherapy, clinical response in breast cancer is frequently below expectations, in part due to various mechanisms of cancer immune escape that produce tumor variants that are resistant to treatment. Thus, a further understanding of the molecular events underlying immune evasion in breast cancer may guarantee a significant improvement in the clinical success of immunotherapy. Furthermore, nanomedicine provides a promising opportunity to enhance the efficacy of cancer immunotherapy by improving the delivery, retention and release of immunostimulatory agents in targeted cells and tumor tissues. Hence, it can be used to overcome tumor immune escape and increase tumor rejection in numerous malignancies, including breast cancer. In this review, we summarize the current status and emerging trends in nanomedicine-based strategies targeting cancer immune evasion and modulating the immunosuppressive tumor microenvironment, including the inhibition of immunosuppressive cells in the tumor area, the activation of dendritic cells and the stimulation of the specific antitumor T-cell response.

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“…In the last few years, three types of immunotherapeutic strategies have been employed and classified into: "passive", including the infusion of monoclonal antibodies (moAbs), i.e., IgG isotypes that bind and neutralize a target tumor associated with or specific antigen yielding the lysis of cancer cells, or the systemic administration of recombinant cytokines; "active", consisting of the administration of ICIs and vaccines, and "adoptive", which exploits immune system cells to eliminate cancer cells, such as autologous T cell-based therapy [1] (Figure 1). The outcome of ICI-based therapy largely depends on the immunogenic nature of the tumor, as demonstrated by the remarkable response and survival gain obtained in melanoma and small cell lung cancer treatment [2,3].…”

Section: Rationale Of Immune-based Therapy In Breast Cancermentioning

confidence: 99%

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

Carlino

Diana²,

Piccolo

et al. 2022

Cancers

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Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a “cold tumor”, exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.

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Immunotherapy in Breast Cancer: When, How, and What Challenges?

Cited by 44 publications

References 114 publications

Drug Metabolism for the Identification of Clinical Biomarkers in Breast Cancer

Drug Metabolism for the Identification of Clinical Biomarkers in Breast Cancer

Nanomedicine as a Promising Tool to Overcome Immune Escape in Breast Cancer

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

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