scholarly journals Clinical Data on Immunotherapy in Breast Cancer

Breast Care ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. 450-469
Author(s):  
Julia Caroline Radosa ◽  
Lisa Stotz ◽  
Carolin Müller ◽  
Askin Canguel Kaya ◽  
Erich-Franz Solomayer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
First Line ◽  
Metastatic Setting ◽  
Epidermal Growth

<b><i>Background:</i></b> Breast cancer has traditionally been considered to have a low immunogenic potential compared to other tumor entities. <b><i>Summary:</i></b> The most extensively studied immunotherapeutic agents for breast cancer to date are immune checkpoint inhibitors, with the results of the IMpassion130 trial leading to the approval of atezolizumab plus nab-paclitaxel for first-line treatment of programmed cell death ligand 1-positive, metastatic, triple-negative breast cancer, and studies in earlier stages have yielded promising results. Other immunotherapeutic options being assessed in phases 2 and 3 trials include vaccine-based therapies and treatment with anti-human epidermal growth factor receptor 2 (H-directed immune-linked antibodies) and substances evaluated in early clinical trials as cellular therapies (adoptive cell therapy and chimeric antigen receptor T cells). <b><i>Key Messages:</i></b> Immunotherapy is an emerging modality for the treatment of breast cancer, as evidenced by the plethora of preclinical and clinical concepts and ongoing trials. Early studies established the role of immunotherapeutic agents in the metastatic setting. Ongoing studies will expand our knowledge about the timing of administration, best partners for combination therapy, and predictive biomarkers to guide immunotherapy for breast cancer.

scholarly journals Clinical Progress of PD-1/L1 Inhibitors in Breast Cancer Immunotherapy

2022 ◽  
Vol 11 ◽  
Author(s):  
Fei Chen ◽  
Naifei Chen ◽  
Yangyang Gao ◽  
Lin Jia ◽  
Zheng Lyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Clinical Trial Data ◽  
First Line ◽  
Hormone Receptor Positive ◽  
Different Types ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Breast cancer is a major killer of women’s health worldwide. While breast cancer is thought to have lower immunogenicity compared with other solid tumors, combination therapy is able to improve the immunogenicity of the tumor and sensitize breast cancer cells to immunotherapy. Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been largely explored in the field of breast cancer, including both early and advanced disease. Immunotherapy for triple-negative breast cancer (TNBC) has been the most studied, and the PD-L1 inhibitor atezolizumab combined with nab-paclitaxel has been used in the first-line treatment of TNBC. Immunotherapeutic data for human epidermal growth factor receptor-positive and hormone receptor-positive breast cancer are also accumulating. This review summarizes the clinical trial data of ICIs or ICI-containing therapies in different types and stages of breast cancer.

scholarly journals Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Li ◽  
Zhijun Zhan ◽  
Xuemin Yin ◽  
Shujun Fu ◽  
Xiyun Deng
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Parp Inhibitors ◽  
Great Effort ◽  
Clinical Investigations ◽  
Epidermal Growth

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression and the absence of human epidermal growth factor receptor 2 (HER2) expression/amplification. Conventional chemotherapy is the mainstay of systemic treatment for TNBC. However, lack of molecular targeted therapies and poor prognosis of TNBC patients have prompted a great effort to discover effective targets for improving the clinical outcomes. For now, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi’s) and immune checkpoint inhibitors have been approved for the treatment of TNBC. Moreover, agents that target signal transduction, angiogenesis, epigenetic modifications, and cell cycle are under active preclinical or clinical investigations. In this review, we highlight the current major developments in targeted therapies of TNBC, with some descriptions about their (dis)advantages and future perspectives.

scholarly journals Carboplatin-Cyclophosphamide or Paclitaxel without or with Bevacizumab as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (BOOG 2013-01)

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Annelot G.J. van Rossum ◽  
Ingrid A.M. Mandjes ◽  
Erik van Werkhoven ◽  
Harm van Tinteren ◽  
A. Elise van Leeuwen-Stok ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
First Line ◽  
Significant Treatment ◽  
Individual Agent ◽  
Efficacy Analysis

<b><i>Background:</i></b> The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. <b><i>Methods:</i></b> The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC ± B or P ± B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. <b><i>Results:</i></b> In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33–1.08; <i>p</i> = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (<i>p</i><sub>interaction</sub> = 0.69). <b><i>Conclusions:</i></b>CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit.

scholarly journals How I treat gastric adenocarcinoma

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 2) ◽  
pp. e000521 ◽  
Author(s):  
Maria Alsina ◽  
Josep Maria Miquel ◽  
Marc Diez ◽  
Sandra Castro ◽  
Josep Tabernero
Keyword(s):  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Metastatic Setting ◽  
Optimal Setting ◽  
Epidermal Growth

Gastric and gastro-oesophageal junction cancer (GC) represents a worldwide problem, this being the fifth most common malignancy. The fragility of patients with GC together with the aggressiveness of this tumour makes it as one of the most difficult neoplasias to manage. This article summarises the main strategies for treating patients with GC. Correct assessment of patients with GC requires a multidisciplinary evaluation and close follow-up. For patients with resectable tumours, perioperative chemotherapy should be always considered, especially in the neoadjuvant setting given its capacity for tumour downstaging and eradication of micro-metastases. In the metastatic setting, first-line and second-line treatment improve survival and quality of life in patients with GC. In this setting, only trastuzumab as first-line therapy in patients with human epidermal growth factor receptor 2 positive tumours and ramucirumab as second-line therapy have demonstrated a clear survival improvement. The lack of adequate biomarker selection and the intrinsic heterogeneity of these tumours have jeopardised the possible usefulness of many other targeted agents. Finally, when considering GC carcinogenesis as a multiple stepwise process from initial inflammation starting in the gastric epithelia, immune checkpoint inhibitors may improve the survival of these patients, although the optimal setting for their activity has yet to be fully elucidated.

scholarly journals A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S32783 ◽  
Author(s):  
Simon B. Zeichner ◽  
Hiromi Terawaki ◽  
Keerthi Gogineni
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Symptomatic Disease ◽  
Metastatic Setting ◽  
Epidermal Growth ◽  
New Treatment

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

scholarly journals High Intrinsic Expression of P-glycoprotein and Breast Cancer Resistance Protein in Canine Mammary Carcinomas Regardless of Immunophenotype and Outcome

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 658
Author(s):  
Michela Levi ◽  
Luisa Vera Muscatello ◽  
Barbara Brunetti ◽  
Cinzia Benazzi ◽  
Federico Parenti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Breast Cancer Resistance Protein ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Epidermal Growth ◽  
Resistance Protein

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are major actors in multidrug resistance (MDR) phenomenon in both human and canine mammary carcinomas (CMCs). The aim of this study was to investigate an association between the intrinsic expression of P-gp and BCRP compared to the immunophenotypes and outcome in CMCs. Fifty CMCs were evaluated at immunohistochemistry (IHC) for P-gp, BCRP, Estrogen receptor alpha (ER), Progesterone receptors (PR), Human Epidermal Growth Factor Receptor type 2 (HER2), basal cytokeratins 5/6 (CK5/6), Epidermal Growth Factor Receptor 1 (EGFR), and Ki67 proliferation index. P-gp and BCRP positive cases were, respectively, 52% and 74.5%, with a significantly higher expression of BCRP than P-gp. Five immunophenotypes were defined in 37 out of 50 CMCs: 9 (24.3%) Luminal A, 5 (13.5%) Luminal B, 9 (24.3%) HER2 overexpressing, 9 (24.3%) Triple-negative basal-like, and 5 (13.5%) Triple-negative non-basal-like. In all CMCs at least one marker was expressed. Follow-up data were available for 25 animals. The average cancer-specific survival was 739 ± 444 days. A number of CMCs bear a high expression of P-gp and BCRP but no significant association was found between their expression and the immunophenotypes, Ki67 index, the histological grade, and tumor-related death.

scholarly journals Trastuzumab administration during pregnancy: un update

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Angeliki Andrikopoulou ◽  
Kleoniki Apostolidou ◽  
Spyridoula Chatzinikolaou ◽  
Garyfalia Bletsa ◽  
Eleni Zografos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
First Trimester ◽  
Systemic Review ◽  
Third Trimester ◽  
Her2 Positive ◽  
Exact Test ◽  
Metastatic Setting ◽  
Epidermal Growth

Abstract Background Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. Methods Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines. Results A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. Conclusions Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.

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