The Use of Atezolizumab + Nab-Paclitaxel for Women with PD- L1 Positive Advanced Triple-Negative Breast Cancer

2021 ◽  
Vol 8 (7) ◽  
pp. 36-43
Author(s):  
Vahideh Beygi Rezagholi ◽  
Sheby Elsa George ◽  
Gouthami. U
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Tumor Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is an uncommon subtype of breast cancer that constitutes 15-20% of cases which has a poorer prognosis and lower survival rates (approximately 18 months or less with available treatments) compared to other types of breast cancer. As the name suggests, TNBC is immunohistologically marked by the lack of expression of factors namely estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2)/NEU gene. TNBC is characterized by high grades of Tumor-Infiltrating lymphocytes (TILs), programmed-death ligand 1 (PD-L1) expression, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as observed in other cancers too. Hence, metastatic TNBC (mTNBC) therapy focuses on the advancement of immune checkpoint inhibitors which block the above immune checkpoint proteins. The use of Atezolizumab (anti-PD-L1) in combination with nab-paclitaxel (chemotherapy agent) has been marked as a relevant advance in the treatment of metastatic, PD-L1-positive TNBC. It is better to consider advanced and approved diagnostic (VENTANA PD-L1 SP142 assay) in patients who get benefit from treatment with Atezolizumab plus nab-paclitaxel. Keywords: Triple Negative Breast Cancer (TNBC), Atezolizumab, Nab-paclitaxel, Chemotherapy.

scholarly journals Immunomodulating Therapies in Breast Cancer—From Prognosis to Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4883
Author(s):  
Marcus Schmidt ◽  
Anne-Sophie Heimes
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes

The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the “immune checkpoint”. Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as “brakes” on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.

scholarly journals Case Report: A Case Study Documenting the Activity of Atezolizumab in a PD-L1-Negative Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Fara Brasó-Maristany ◽  
Miriam Sansó ◽  
Nuria Chic ◽  
Débora Martínez ◽  
Blanca González-Farré ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Genomic Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Durable Response ◽  
Tumor Mutational Burden

The immune checkpoint inhibitor atezolizumab is approved for PD-L1-positive triple-negative breast cancer (TNBC). However, no activity of atezolizumab in PD-L1-negative TNBC has been reported to date. Here, we present the case study of a woman with TNBC with low tumor infiltrating lymphocytes and PD-L1-negative disease, which achieved a significant response to atezolizumab monotherapy and durable response after the combination of atezolizumab and nab-paclitaxel. The comprehensive genomic analysis that we performed in her tumor and plasma samples revealed high tumor mutational burden (TMB), presence of the APOBEC genetic signatures, high expression of the tumor inflammation signature, and a HER2-enriched subtype by the PAM50 assay. Some of these biomarkers have been shown to independently predict response to immunotherapy in other tumors and may explain the durable response in our patient. Our work warrants further translational studies to identify biomarkers of response to immune checkpoint inhibitors in TNBC beyond PD-L1 expression and to better select patients that will benefit from immunotherapy.

scholarly journals Prospects of Immunotherapy for Triple-Negative Breast Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Dan Qiu ◽  
Guijuan Zhang ◽  
Xianxin Yan ◽  
Xinqin Xiao ◽  
Xinyi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Cellular Immunotherapy ◽  
T Cell Dysfunction ◽  
The Impact

In the classification and typing of breast cancer, triple-negative breast cancer (TNBC) is one type of refractory breast cancer, while chemotherapy stays in the traditional treatment methods. However, the impact of chemotherapy is short-lived and may lead to recurrence due to incomplete killing of tumor cells. The occurrence, development, and relapse of breast cancer are relevant to T cell dysfunction, multiplied expression of related immune checkpoint molecules (ICIs) such as programmed death receptor 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) produce immunosuppressive effect. Immunotherapy (namely, immune checkpoint inhibitors, adoptive cellular immunotherapy, CAR-T immunotherapy and some potential treatments) provides new hope in TNBC. This review focuses on the new immune strategies of TNBC patients.

scholarly journals Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ayca Gucalp ◽  
Tiffany A. Traina
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Cytotoxic Chemotherapy ◽  
Breast Cancers ◽  
Targeted Agents ◽  
Increased Risk ◽  
Disproportionate Number

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

scholarly journals Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Karima Oualla ◽  
Loay Kassem ◽  
Lamiae Nouiakh ◽  
Lamiae Amaadour ◽  
Zineb Benbrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Poor Outcomes ◽  
Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%–20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.

scholarly journals Targeted Therapies in Triple-Negative Breast Cancer

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Frederik Marmé ◽  
Andreas Schneeweiss
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Receptor Subtype

Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A antibody, is the only targeted agent with an approval for the therapy of metastatic breast cancer, but does not provide a specific benefit in the TNBC subtype. This review discusses the current clinical developments in targeted approaches for TNBC, including anti-angiogenic therapies, epidermal growth factor receptor (EGFR)-targeted therapies, poly(ADP-ribose) polymerase (PARP) inhibitors and platinum salts, as well as novel strategies using immune-checkpoint inhibitors, which have recently demonstrated first promising results. Strategies focusing on specific subtypes of TNBC like anti-androgenic therapies for the luminal androgen receptor subtype (LAR) and others are also discussed.

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