Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives (original) (raw)
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The Journal of Middle East and North Africa Sciences, 2022
Triple negative breast cancer TNBC is the type of breast cancer that does not have Estrogen receptor, Progesterone receptor and human epidermal growth factor receptors 2 (HER2) when stained with the Immunohistochemistry stains. As it's lacking the targets for most chemotherapy medications, it has a more aggressive course, a poor prognosis, higher chances of relapse and usually diagnosed at a later stage. In this review, we are illustrating how the immune system can be manipulated to attack the micro-environment that the cancer creates to escape and thrive. Also, we are discussing the signaling pathways of the immune system on which the immunotherapy medications were based and the different chemotherapy options that are used in the same regiment for management of TNBC.
Immunotherapy for triple-negative breast cancer: Existing challenges and exciting prospects
Drug Resistance Updates, 2017
Patients with breast tumors that do not express the estrogen receptor, the progesterone receptor, nor Her-2/neu are hence termed "triple negatives", and generally have a poor prognosis, with high rates of systemic recurrence and refractoriness to conventional therapy regardless of the choice of adjuvant treatment. Thus, more effective therapeutic options are sorely needed for triple-negative breast cancer (TNBC), which occurs in approximately 20% of diagnosed breast cancers. In recent years, exploiting intrinsic mechanisms of the host immune system to eradicate cancer cells has achieved impressive success, and the advances in
Triple negative breast cancer: Immunogenicity, tumor microenvironment, and immunotherapy
Frontiers in Genetics
Triple negative breast cancer (TNBC) is a biologically diverse subtype of breast cancer characterized by genomic and transcriptional heterogeneity and exhibiting aggressive clinical behaviour and poor prognosis. In recent years, emphasis has been placed on the identification of mechanisms underlying the complex genomic and biological profile of TNBC, aiming to tailor treatment strategies. High immunogenicity, specific immune activation signatures, higher expression of immunosuppressive genes and higher levels of stromal Tumor Infiltrating Lymphocytes, constitute some of the key elements of the immune driven landscape associated with TNBC. The unprecedented response of TNBC to immunotherapy has undoubtedly changed the standard of care in this disease both in the early and the metastatic setting. However, the extent of interplay between immune infiltration and mutational signatures in TNBC is yet to be fully unravelled. In the present review, we present clinical evidence on the immuno...
Medical Oncology
Triple negative breast cancer (TNBC) portraying deficient expression of estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) is known to be the most aggressive subtype associated with poor prognosis and interventional strategies limited to chemotherapy and breast conserving surgery. Some TNBC incidences have also been reported with positive circ-HER2 expression thus rendering circ-HER2 a potential immunotherapy target to direct drug development. Resistance and recurrence reported with traditional approaches has led us towards the application of immunotherapeutic interventions owing to their anti-tumor efficacy. This review provides an elaborative insight on potential molecular biomarkers to be targeted by immunotherapy. Additionally, clinical trials proposing the application of immunotherapy in neoadjuvant, adjuvant and metastatic TNBC setting have also been included. The gathered evidence indicates a positive application of immunotherapy in TNBC with therapeutic limitation available only owing to the possibility of adverse events which can be dealt considering risk-to-benefit ratio. Furthermore, potential targets to aim for therapeutic vaccines along with evidence from clinical trials have also been mentioned. Keywords Triple-negative breast cancer • Immunotherapy • Cancer vaccine • Immune checkpoint inhibitors • Neoadjuvant • Adjuvant • Metastasis Abbreviations ADCC Antibody-dependent cellular cytotoxicity BC Breast Cancer BL1/BL2 Basal-like 1/Basal-like 2 CART Chimeric antigen receptor T-cell therapy CBR Clinical benefit rate CEA Carcinoembryogenic antigen circ-HER2 Circular human-epidermal growth factor CR Complete response CTLA-4 Cytotoxic T lymphocyte-associated antigen-4 CVs Cancer vaccines DC Dendritic cells DCR Disease control rate DOR Duration of response EFS Event-free survival EGFR Epidermal growth factor receptor ER Estrogen receptor ERα+ Estrogen receptor a-positive GP2 Glycoprotein 2 HER2 Human-epidermal growth factor hTERT Human telomerase reverse transcriptase
Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting
Clinical Medicine Insights: Oncology, 2016
Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New...
Cancer and Metastasis Reviews, 2022
Triple-negative breast cancer (TNBC), which comprises 10-20% of all breast malignancies, remains a subtype with the most dismal prognosis. TNBC cells, due to lack of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor-2 (HER-2) receptor expression, are insensitive to all known endocrine and anti-HER-2-targeted therapies. As a result, chemotherapy remains the standard of care for this subgroup of patients, in whom a high recurrence rate and poor overall survival are observed. The biology of TNBC is distinctive, not only in comparison to other breast cancers, but its natural course differs among individuals. This heterogeneity makes it even harder to define new therapeutic targets or predictive factors. Therefore, an urgent need to develop effective therapies exists, as only 20% of TNBC patients treated in a neoadjuvant and adjuvant setting achieve a pathological complete response (pCR), which is a strong surrogate marker for longer overall survival (OS). The remaining 80% are exposed to highly toxic treatment that causes a significant decrease in quality of life, while at the same time providing little clinical benefit. The efficacy of palliative chemotherapy is even more disappointing. Following the spread of the disease, most commonly to visceral organs or to the brain, the mean survival time is only 10.2 months [1]. Initially, the success of immunotherapy in treating malignancies exhibiting a pessimistic prognosis, such as malignant melanoma or lung cancer, raised hope for TNBC patients.
Immunotherapy in Triple-Negative Breast Cancer: Present and Future
Current Breast Cancer Reports, 2019
Purpose of Review Immunotherapy is emerging as an effective treatment option for metastatic triple-negative breast cancer. In this review, we summarize clinical data of immunotherapy in triple-negative breast cancer and comment on future directions in the field. Recent Findings IMpassion130 was a phase III trial that demonstrated progression-free survival benefit, and potentially overall survival benefit, of first-line chemotherapy (nab-paclitaxel) plus anti-programmed death ligand 1 (PD-L1) atezolizumab, among PD-L1-positive metastatic triple-negative breast cancers. Studies are ongoing to evaluate other combination therapies with immune checkpoint blockade in TNBC, and to evaluate efficacy in PD-L1-negative tumors and in later lines of therapy. Summary Immunotherapy is now a standard option in the treatment of triple-negative breast cancer. Ongoing trials may expand the degree of clinical benefit. Further work is ongoing to identify novel predictive biomarkers, which in the future...
The Immune Landscape of Breast Cancer: Strategies for Overcoming Immunotherapy Resistance
Cancers
Breast cancer (BC) has traditionally been considered to be not inherently immunogenic and insufficiently represented by immune cell infiltrates. Therefore, for a long time, it was thought that the immunotherapies targeting this type of cancer and its microenvironment were not justified and would not bring benefits for breast cancer patients. Nevertheless, to date, a considerable number of reports have indicated tumor-infiltrating lymphocytes (TILs) as a prognostic and clinically relevant biomarker in breast cancer. A high TILs expression has been demonstrated in primary tumors, of both, HER2-positive BC and triple-negative (TNBC), of patients before treatment, as well as after treatment with adjuvant and neoadjuvant chemotherapy. Another milestone was reached in advanced TNBC immunotherapy with the help of the immune checkpoint inhibitors directed against the PD-L1 molecule. Although those findings, together with the recent developments in chimeric antigen receptor T cell therapies,...
Immunotherapy in triple-negative breast cancer: A literature review and new advances
World journal of clinical oncology, 2022
Purpose of Review Immunotherapy is emerging as an effective treatment option for metastatic triple-negative breast cancer. In this review, we summarize clinical data of immunotherapy in triple-negative breast cancer and comment on future directions in the field. Recent Findings IMpassion130 was a phase III trial that demonstrated progression-free survival benefit, and potentially overall survival benefit, of first-line chemotherapy (nab-paclitaxel) plus anti-programmed death ligand 1 (PD-L1) atezolizumab, among PD-L1-positive metastatic triple-negative breast cancers. Studies are ongoing to evaluate other combination therapies with immune checkpoint blockade in TNBC, and to evaluate efficacy in PD-L1-negative tumors and in later lines of therapy. Summary Immunotherapy is now a standard option in the treatment of triple-negative breast cancer. Ongoing trials may expand the degree of clinical benefit. Further work is ongoing to identify novel predictive biomarkers, which in the future may enable a personalized approach of combination immunotherapy.
Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice
Cancers
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, man...