scholarly journals The use of multi-omics data and approaches in breast cancer immunotherapy: a review

2020 ◽  
Vol 16 (27) ◽  
pp. 2101-2119
Author(s):  
Ka Lun Leung ◽  
Devika Verma ◽  
Younus Jamal Azam ◽  
Emyr Bakker
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Clinical Trial Design ◽  
Immune Checkpoint Blockade ◽  
Omics Data ◽  
Treatment Side Effects ◽  
The Usa ◽  
Type Data ◽  
Target Cancer

Breast cancer is projected to be the most common cancer in women in 2020 in the USA. Despite high remission rates treatment side effects remain an issue, hence the interest in novel approaches such as immunotherapies which aim to utilize patients’ immune systems to target cancer cells. This review summarizes the basics of breast cancer including staging and treatment options, followed by a discussion on immunotherapy, including immune checkpoint blockade. After this, examples of the role of omics-type data and computational biology/bioinformatics in breast cancer are explored. Ultimately, there are several promising areas to investigate such as the prediction of neoantigens and the use of multi-omics data to direct research, with noted appropriate in clinical trial design in terms of end points.

scholarly journals Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3357
Author(s):  
Hongmei Zheng ◽  
Sumit Siddharth ◽  
Sheetal Parida ◽  
Xinhong Wu ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Combined Treatment ◽  
High Mobility ◽  
Sphingosine 1 Phosphate ◽  
Molecular Patterns

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

scholarly journals Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 957 ◽  
Author(s):  
Milica Nedeljković ◽  
Ana Damjanović
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Chemotherapy Resistance ◽  
Standard Of Care ◽  
Drug Efflux ◽  
Molecular Signatures ◽  
Chemotherapy Treatment ◽  
Multiple Signaling

Triple-negative (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options. Chemotherapy remains the standard of care for TNBC treatment, but unfortunately, patients frequently develop resistance. Accordingly, in recent years, tremendous effort has been made into elucidating the mechanisms of TNBC chemoresistance with the goal of identifying new molecular targets. It has become evident that the development of TNBC chemoresistance is multifaceted and based on the elaborate interplay of the tumor microenvironment, drug efflux, cancer stem cells, and bulk tumor cells. Alterations of multiple signaling pathways govern these interactions. Moreover, TNBC’s high heterogeneity, highlighted in the existence of several molecular signatures, presents a significant obstacle to successful treatment. In the present, in-depth review, we explore the contribution of key mechanisms to TNBC chemoresistance as well as emerging strategies to overcome them. We discuss novel anti-tumor agents that target the components of these mechanisms and pay special attention to their current clinical development while emphasizing the challenges still ahead of successful TNBC management. The evidence presented in this review outlines the role of crucial pathways in TNBC survival following chemotherapy treatment and highlights the importance of using combinatorial drug strategies and incorporating biomarkers in clinical studies.

Diagnosis of Metastatic Breast Cancer—A Case Report Using Molecular Cancer Classification

2011 ◽  
Vol 07 (02) ◽  
pp. 116
Author(s):  
Yogesh Gandhi ◽  
Sunil Gandhi ◽  
◽  
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Effective Treatment ◽  
Cancer Diagnosis ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Complete Response ◽  
Molecular Profiling ◽  
History Of

An accurate cancer diagnosis is critical as it can direct the use of site-directed, and potentially more effective, treatment options for specific types of cancer. A differential or uncertain diagnosis could prevent cancer patients from receiving optimal treatment, thus affecting their overall prognosis. Advances in molecular technology have led to the development of molecular cancer classifiers that can direct or confirm the diagnosis of metastatic cancers which would otherwise be considered uncertain or unknown. This case report describes the role of molecular diagnostics in the evaluation of a patient with a large pancreatic mass and a history of breast cancer. Results from a 92-gene molecular profiling assay (CancerTYPE ID®) predicted that this new mass was breast cancer. This diagnosis allowed for effective treatment and complete response in this patient.

Impact of treatment line on outcomes with salvage ipilimumab + nivolumab in metastatic renal cell carcinoma (mRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17092-e17092
Author(s):  
Ritesh Kotecha ◽  
Chung-Han Lee ◽  
Andrea Knezevic ◽  
Neil J. Shah ◽  
Maria Isabel Carlo ◽  
...  
Keyword(s):  
Treatment Options ◽  
Immune Checkpoint Blockade ◽  
Clinical Progression ◽  
Start Time ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Time To Treatment Failure ◽  
Treatment Sequencing ◽  
Line Setting

e17092 Background: With the approval of ipilimumab plus nivolumab (I+N) and other immune checkpoint blockade (ICB) based combinations in the first-line setting, the role of I+N for salvage is of high interest for treatment sequencing, yet data is limited. Methods: We conducted a retrospective review of mRCC patients (pts) treated with I+N in the second-line (2L) and beyond settings at MSKCC between 2013-2019. Pt demographics, treatment history and toxicity were compiled. IMDC-risk status was calculated at I+N therapy start. Time to treatment failure (TTF) was defined as earliest date of clinical progression, therapy change or death, and overall survival (OS) was estimated by Kaplan-Meier method. Results: 36 pts received I+N in the 2+L setting, including 31/36 with clear-cell histology. Evaluable IMDC-risk at I+N start was favorable in 1/35 and intermediate-poor in 34/35 pts. The most common 1L therapies were anti-VEGF (22/36) and VEGF + ICB (6/36). 11/36 pts had ICB treatment exposure prior to I+N therapy. I+N therapy in the 2L, 3L and 4L was in 21/36, 8/36 and 7/36 pts, respectively, and 7/36 pts continue I+N at data cut-off. 8/36 pts discontinued I+N due to toxicity, 20/36 pts discontinued therapy due to disease progression, and 1 pt discontinued per pt preference. Cohort median OS was 14.8 months (95%CI: 4.2-44). Overall median TTF was 5.0 months (95%CI: 2.9-14.4), and TTF per 2L, 3L and 4+L was 8.3, 8.9 and 2.5 months, respectively. The number of patients who completed all 4 I+N induction cycles in the 2L, 3L, and 4+L was 11/21 (52%), 5/8 (63%), and 1/7 (14%). The number of patients who subsequently received nivolumab maintenance therapy after induction was 16/21 (76%) in the 2L, 1/8 (13%) in the 3L, and 0/7 (0%) in 4+L. Conclusions: With emerging treatment options for mRCC, this study reveals activity and safety for I+N in 2+L settings. In this limited cohort, completion of induction ipilimumab and use of maintenance nivolumab decline in later-line settings, suggesting limitations as salvage therapy. [Table: see text]

scholarly journals An overview of immune checkpoint inhibitors in breast cancer

2020 ◽  
Vol 1 (6) ◽  
Author(s):  
Federica Miglietta ◽  
Maria Silvia Cona ◽  
Maria Vittoria Dieci ◽  
Valentina Guarneri ◽  
Nicla La Verde
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Novel Treatment ◽  
Near Future ◽  
Triple Negative Subtype

Although breast cancer is not traditionally considered an immunogenic type of tumor, the combination of immunotherapy and chemotherapy has recently emerged as a novel treatment option in triple-negative subtype in the advanced setting and other similar combinations of immune checkpoint inhibitors with chemotherapy are expected to become part of the neoadjuvant management in the near future. In addition, encouraging results have been observed with the combination of immune checkpoint blockade with diverse biological agents, including anti-HER2 agents, CDK 4/6 inhibitors, PARP-inhibitors. The present review summarized the available evidence coming from clinical trials on the role of immune checkpoint inhibitors in the management of breast cancer, both in advanced and early setting.

Breast cancer: understanding etiology, addressing molecular signaling pathways, identifying therapeutic targets and strategizing the treatment

2021 ◽  
Vol 12 (3) ◽  
pp. 1757-1769
Author(s):  
Preeti Tanaji Mane ◽  
Sangram Prakash Patil ◽  
Balaji Sopanrao Wakure ◽  
Pravin Shridhar Wakte
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Treatment Options ◽  
Current Treatment ◽  
Vital Role ◽  
Molecular Signaling ◽  
Breast Tumorigenesis ◽  
Non Coding Rnas ◽  
Cycle Regulation

Breast cancer has messed the life of a greater number of women being the most common cancer affecting them worldwide. A number of risk factors contribute the breast malignancy, however, genetic drift is accountable the most. Depending on the cell origin, invasiveness and receptors involved, breast cancer is classified into various subtypes. The accurate diagnosis of breast cancer is important as it defines the prognosis and directs the type of treatment required. A number of major signaling pathways involved in breast tumorigenesis and its development include estrogen receptors (ERs), HER2, Wnt/β-catenin, Notch, Hedgehog (Hh), PI3K and mTOR pathway. Furthermore, certain enzymes like Cyclin dependent kinases and breast tumor kinases also play a vital role in cell cycle regulation and therefore, in the development of breast neoplasms. Recent studies have also enlightened the role of non-coding RNAs in breast cancer development. This review discusses various aspects of breast cancer such as its etiology, subtypes, various signaling pathways involved, targets projected by these pathways and the current treatment options based on a few of these targets. Also, the role of different genes, enzymes and non-coding RNAs related to breast tumorigenesis and development is discussed.

The application of immune checkpoint blockade in breast cancer and the emerging role of nanoparticle

2021 ◽  
Author(s):  
Elham Masoumi ◽  
Sahar Tahaghoghi-Hajghorbani ◽  
Leila Jafarzadeh ◽  
Mohammad-Javad Sanaei ◽  
Atieh Pourbagheri-Sigaroodi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

scholarly journals Clinical Theragnostic Relationship between Drug-Resistance Specific miRNA Expressions, Chemotherapeutic Resistance, and Sensitivity in Breast Cancer: A Systematic Review and Meta-Analysis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1250 ◽  
Author(s):  
Jayaraj ◽  
Nayagam ◽  
Kar ◽  
Sathyakumar ◽  
Mohammed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Drug Targets ◽  
Meta Analysis ◽  
Treatment Options ◽  
Rank Correlation ◽  
P Value ◽  
Bibliographic Search ◽  
Trim And Fill

Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran’s Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger’s bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508–1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.

Trial in progress: Phase I/II study of radiation therapy followed by intrathecal trastuzumab/pertuzumab in the management of HER2+ breast leptomeningeal disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS1099-TPS1099
Author(s):  
Kamran A. Ahmed ◽  
Youngchul Kim ◽  
Michelle DeJesus ◽  
Priya Kumthekar ◽  
Nicole Olivia Williams ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Phase I ◽  
Systemic Disease ◽  
Symptomatic Relief ◽  
Treatment Options ◽  
Leptomeningeal Disease ◽  
Breast Cancer Patients ◽  
Open Label

TPS1099 Background: HER2+ breast cancer patients with leptomeningeal disease (LMD) represent a poor prognosis population with a high unmet clinical need. Although a multitude of treatment options are available for the management of systemic disease, once metastases travel to the leptomeninges, patients have a lack of treatment options aside from traditional local approaches. Data from a phase I/II study reveals intrathecal (IT) trastuzumab to be well tolerated with improved overall survival (OS) compared to historical controls in HER2+ breast LMD. Radiotherapy can improve the flow of IT therapy through the cerebrospinal fluid (CSF) and provide symptomatic relief. The monoclonal antibody pertuzumab is used in conjunction with trastuzumab in the management of metastatic and localized HER2+ breast cancer. Given the role of radiotherapy in the management of LMD along with the role of pertuzumab in the management of HER2+ breast cancer, there is a strong clinical rationale to combine radiotherapy with IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. Methods: The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of radiation therapy followed by IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. HER2+ LMD patients identified by magnetic resonance imaging (MRI) and/or CSF cytology, ≥ 18, with a life expectancy > 8 weeks are eligible. Treatment is initiated with radiotherapy, whole brain radiotherapy and/or focal brain/spine radiation followed by IT trastuzumab/pertuzumab. Safety and feasibility will be monitored by a modified toxicity probability interval-2 (mTPI-2) design. Dose reductions of IT trastuzumab will not be allowed. Once the maximum tolerated dose of IT pertuzumab is determined, the phase II portion of the study will commence to determine OS. Secondary objectives involve defining the CSF pharmacokinetics of IT trastuzumab/pertuzumab, evaluating the response rate (leptomeningeal and parenchymal), and progression free survival (leptomeningeal and parenchymal) following IT trastuzumab/pertuzumab. In the phase 2 portion, a single-arm two-stage trial is designed using the Restricted-Kwak-and-Jung’s Method. The primary endpoint is one-year OS. An interim analysis will be performed after 20 patients are enrolled. This study is open with 1 patient enrolled at the time of submission. Clinical trial information: NCT04588545 .

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