Advances in Breast Cancer Research and Treatment

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (29 December 2023) | Viewed by 20156

Special Issue Editors

Peking University People's Hospital, Beijing, China
Interests: breast cancer; bioinformatics; oncology

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Guest Editor
Peking University Cancer Hospital, Beijing, China
Interests: biophysics; single molecular assay; evolutionary genetics; molecular biology; genetics
International Cancer Center, Shenzhen University, Shenzhen, China
Interests: immuno-oncology

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Guest Editor
Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, 10124 Torino, Italy
Interests: autophagy; lysosomes; lysosomal cell death; apoptosis; anticancer drug resistance; breast cancer; hepatocellular carcinoma; protein turnover; molecular determinants of protein instability

Special Issue Information

Dear Colleagues,

Breast cancer is the most frequent malignancy worldwide. Recent developments in both clinical research and basic research have promoted our understanding and management of breast cancer.

This Special Issue on “Advances in Breast Cancer Research and Treatment” focuses on recent developments in clinical and basic research of breast cancer. We are pleased to invite you to submit research papers, reviews, communications, etc. for this Special Issue.

Research topics include, but are not limited to, biomarker identification, clinical pharmacology, histological and molecular subtypes, cancer genetics, medical imaging, progress in surgical and radiotherapy, and targeted therapy. Translational research and basic research are also welcome.

We look forward to receiving your contributions.

Dr. Taobo Hu
Dr. Mengping Long
Dr. Lei Wang
Dr. Riccardo Autelli
Guest Editors

Manuscript Submission Information

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Keywords

  • breast cancer
  • clinical pharmacology
  • translational research
  • cancer biomarker
  • targeted therapy
  • medical imaging
  • surgery

Published Papers (11 papers)

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Research

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21 pages, 181343 KiB  
Article
Improved Breast Cancer Classification through Combining Transfer Learning and Attention Mechanism
by Asadulla Ashurov, Samia Allaoua Chelloug, Alexey Tselykh, Mohammed Saleh Ali Muthanna, Ammar Muthanna and Mehdhar S. A. M. Al-Gaashani
Life 2023, 13(9), 1945; https://doi.org/10.3390/life13091945 - 21 Sep 2023
Cited by 4 | Viewed by 1726
Abstract
Breast cancer, a leading cause of female mortality worldwide, poses a significant health challenge. Recent advancements in deep learning techniques have revolutionized breast cancer pathology by enabling accurate image classification. Various imaging methods, such as mammography, CT, MRI, ultrasound, and biopsies, aid in [...] Read more.
Breast cancer, a leading cause of female mortality worldwide, poses a significant health challenge. Recent advancements in deep learning techniques have revolutionized breast cancer pathology by enabling accurate image classification. Various imaging methods, such as mammography, CT, MRI, ultrasound, and biopsies, aid in breast cancer detection. Computer-assisted pathological image classification is of paramount importance for breast cancer diagnosis. This study introduces a novel approach to breast cancer histopathological image classification. It leverages modified pre-trained CNN models and attention mechanisms to enhance model interpretability and robustness, emphasizing localized features and enabling accurate discrimination of complex cases. Our method involves transfer learning with deep CNN models—Xception, VGG16, ResNet50, MobileNet, and DenseNet121—augmented with the convolutional block attention module (CBAM). The pre-trained models are finetuned, and the two CBAM models are incorporated at the end of the pre-trained models. The models are compared to state-of-the-art breast cancer diagnosis approaches and tested for accuracy, precision, recall, and F1 score. The confusion matrices are used to evaluate and visualize the results of the compared models. They help in assessing the models’ performance. The test accuracy rates for the attention mechanism (AM) using the Xception model on the “BreakHis” breast cancer dataset are encouraging at 99.2% and 99.5%. The test accuracy for DenseNet121 with AMs is 99.6%. The proposed approaches also performed better than previous approaches examined in the related studies. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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15 pages, 8429 KiB  
Article
The Role of Diffusion-Weighted Imaging Based on Maximum-Intensity Projection in Young Patients with Marked Background Parenchymal Enhancement on Contrast-Enhanced Breast MRI
by Ga-Eun Park, Bong-Joo Kang, Sung-hun Kim and Na-Young Jung
Life 2023, 13(8), 1744; https://doi.org/10.3390/life13081744 - 14 Aug 2023
Viewed by 857
Abstract
Diffusion-weighted imaging (DWI) utilizing maximum-intensity projection (MIP) was suggested as a cost-effective alternative tool without the risk of gadolinium-based contrast agents. The purpose of this study was to investigate whether DWI MIPs played a supportive role in young (≤60) patients with marked background [...] Read more.
Diffusion-weighted imaging (DWI) utilizing maximum-intensity projection (MIP) was suggested as a cost-effective alternative tool without the risk of gadolinium-based contrast agents. The purpose of this study was to investigate whether DWI MIPs played a supportive role in young (≤60) patients with marked background parenchymal enhancement (BPE) on contrast-enhanced MRI (CE-MRI). The research included 1303 patients with varying degrees of BPE, and correlations between BPE on CE-MRI, the background diffusion signal (BDS) on DWI, and clinical parameters were analyzed. Lesion detection scores were compared between CE-MRI and DWI, with DWI showing higher scores. Among the 186 lesions in 181 patients with marked BPE on CE-MRI, the main lesion on MIPs of CE-MRI was partially or completely seen in 88.7% of cases, while it was not seen in 11.3% of cases. On the other hand, the main lesion on MIPs of DWI was seen in 91.4% of cases, with only 8.6% of cases showing no visibility. DWI achieved higher scores for lesion detection compared to CE-MRI. The presence of a marked BDS was significantly associated with a lower likelihood of a higher DWI score (p < 0.001), and non-mass lesions were associated with a decreased likelihood of a higher DWI score compared with mass lesions (p = 0.196). In conclusion, the inclusion of MIPs of DWI in the preoperative evaluation of breast cancer patients, particularly young women with marked BPE, proved highly beneficial in improving the overall diagnostic process. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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15 pages, 5631 KiB  
Article
Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer
by Jingjin Zhu, Ningning Min, Wenye Gong, Yizhu Chen and Xiru Li
Life 2023, 13(4), 998; https://doi.org/10.3390/life13040998 - 12 Apr 2023
Cited by 1 | Viewed by 2005
Abstract
The relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore [...] Read more.
The relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore the potential co-pathogenesis and prognostic linkage of these two diseases. We used GEO, TCGA, STRING, ssGSEA, and Rstudio to investigate the common differentially expressed genes (DEGs), conduct functional and signaling pathway enrichment analyses, and determine prognostic value between TNBC and NAFLD. GO and KEGG enrichment analyses of the common DEGs showed that they were enriched in leukocyte aggregation, migration and adhesion, apoptosis regulation, and the PPAR signaling pathway. Fourteen candidate hub genes most likely to mediate NAFLD and TNBC occurrence were identified and validation results in a new cohort showed that ITGB2, RAC2, ITGAM, and CYBA were upregulated in both diseases. A univariate Cox analysis suggested that high expression levels of ITGB2, RAC2, ITGAM, and CXCL10 were associated with a good prognosis in TNBC. Immune infiltration analysis of TNBC samples showed that NCF2, ICAM1, and CXCL10 were significantly associated with activated CD8 T cells and activated CD4 T cells. NCF2, CXCL10, and CYBB were correlated with regulatory T cells and myeloid-derived suppressor cells. This study demonstrated that the redox reactions regulated by the NADPH oxidase (NOX) subunit genes and the transport and activation of immune cells regulated by integrins may play a central role in the co-occurrence trend of NAFLD and TNBC. Additionally, ITGB2, RAC2, and ITGAM were upregulated in both diseases and were prognostic protective factors of TNBC; they may be potential therapeutic targets for treatment of TNBC patients with NAFLD, but further experimental studies are still needed. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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15 pages, 2462 KiB  
Article
Clinicopathological Characteristics and Prognostic Profiles of Breast Carcinoma with Neuroendocrine Features
by Yue Qiu, Yongjing Dai, Li Zhu, Xiaopeng Hao, Liping Zhang, Baoshi Bao, Yuhui Chen and Jiandong Wang
Life 2023, 13(2), 532; https://doi.org/10.3390/life13020532 - 15 Feb 2023
Cited by 1 | Viewed by 1112
Abstract
Background: Breast carcinoma with neuroendocrine features includes neuroendocrine neoplasm of the breast and invasive breast cancer with neuroendocrine differentiation. This study aimed to investigate the clinicopathological features and prognosis of this disease according to the fifth edition of the World Health Organization classification [...] Read more.
Background: Breast carcinoma with neuroendocrine features includes neuroendocrine neoplasm of the breast and invasive breast cancer with neuroendocrine differentiation. This study aimed to investigate the clinicopathological features and prognosis of this disease according to the fifth edition of the World Health Organization classification of breast tumors. Materials and Methods: A total of 87 patients with breast carcinoma with neuroendocrine features treated in the First Medical Center, Chinese PLA General Hospital from January 2001 to January 2022 were retrospectively enrolled in this study. Results: More than half of the patients were postmenopausal patients, especially those with neuroendocrine neoplasm (62.96%). There were more patients with human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, and most of them were Luminal B type (71.26%). The multivariate analysis showed that diabetes and stage IV disease were related to the progression-free survival of breast carcinoma with neuroendocrine features patients (p = 0.004 and p < 0.001, respectively). Conclusion: Breast carcinoma with neuroendocrine features tended to be human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, most of them were Luminal B type, and the related factors of progression-free survival were diabetes and stage IV disease. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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18 pages, 3888 KiB  
Article
In Silico Analysis of Publicly Available Transcriptomic Data for the Identification of Triple-Negative Breast Cancer-Specific Biomarkers
by Rachid Kaddoura, Fatma Alqutami, Mohamed Asbaita and Mahmood Hachim
Life 2023, 13(2), 422; https://doi.org/10.3390/life13020422 - 02 Feb 2023
Cited by 2 | Viewed by 2332
Abstract
Background: Breast cancer is the most common type of cancer among women and is classified into multiple subtypes. Triple-negative breast cancer (TNBC) is the most aggressive subtype, with high mortality rates and limited treatment options such as chemotherapy and radiation. Due to the [...] Read more.
Background: Breast cancer is the most common type of cancer among women and is classified into multiple subtypes. Triple-negative breast cancer (TNBC) is the most aggressive subtype, with high mortality rates and limited treatment options such as chemotherapy and radiation. Due to the heterogeneity and complexity of TNBC, there is a lack of reliable biomarkers that can be used to aid in the early diagnosis and prognosis of TNBC in a non-invasive screening method. Aim: This study aims to use in silico methods to identify potential biomarkers for TNBC screening and diagnosis, as well as potential therapeutic markers. Methods: Publicly available transcriptomic data of breast cancer patients published in the NCBI’s GEO database were used in this analysis. Data were analyzed with the online tool GEO2R to identify differentially expressed genes (DEGs). Genes that were differentially expressed in more than 50% of the datasets were selected for further analysis. Metascape, Kaplan-Meier plotter, cBioPortal, and the online tool TIMER were used for functional pathway analysis to identify the biological role and functional pathways associated with these genes. Breast Cancer Gene-Expression Miner v4.7 was used to validify the obtained results in a larger cohort of datasets. Results: A total of 34 genes were identified as differentially expressed in more than half of the datasets. The DEG GATA3 had the highest degree of regulation, and it plays a role in regulating other genes. The estrogen-dependent pathway was the most enriched pathway, involving four crucial genes, including GATA3. The gene FOXA1 was consistently down-regulated in TNBC in all datasets. Conclusions: The shortlisted 34 DEGs will aid clinicians in diagnosing TNBC more accurately as well as developing targeted therapies to improve patient prognosis. In vitro and in vivo studies are further recommended to validate the results of the current study. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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Review

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11 pages, 243 KiB  
Review
Patients’ Perceptions and Attitudes to the Use of Artificial Intelligence in Breast Cancer Diagnosis: A Narrative Review
by Filippo Pesapane, Emilia Giambersio, Benedetta Capetti, Dario Monzani, Roberto Grasso, Luca Nicosia, Anna Rotili, Adriana Sorce, Lorenza Meneghetti, Serena Carriero, Sonia Santicchia, Gianpaolo Carrafiello, Gabriella Pravettoni and Enrico Cassano
Life 2024, 14(4), 454; https://doi.org/10.3390/life14040454 - 29 Mar 2024
Viewed by 703
Abstract
Breast cancer remains the most prevalent cancer among women worldwide, necessitating advancements in diagnostic methods. The integration of artificial intelligence (AI) into mammography has shown promise in enhancing diagnostic accuracy. However, understanding patient perspectives, particularly considering the psychological impact of breast cancer diagnoses, [...] Read more.
Breast cancer remains the most prevalent cancer among women worldwide, necessitating advancements in diagnostic methods. The integration of artificial intelligence (AI) into mammography has shown promise in enhancing diagnostic accuracy. However, understanding patient perspectives, particularly considering the psychological impact of breast cancer diagnoses, is crucial. This narrative review synthesizes literature from 2000 to 2023 to examine breast cancer patients’ attitudes towards AI in breast imaging, focusing on trust, acceptance, and demographic influences on these views. Methodologically, we employed a systematic literature search across databases such as PubMed, Embase, Medline, and Scopus, selecting studies that provided insights into patients’ perceptions of AI in diagnostics. Our review included a sample of seven key studies after rigorous screening, reflecting varied patient trust and acceptance levels towards AI. Overall, we found a clear preference among patients for AI to augment rather than replace the diagnostic process, emphasizing the necessity of radiologists’ expertise in conjunction with AI to enhance decision-making accuracy. This paper highlights the importance of aligning AI implementation in clinical settings with patient needs and expectations, emphasizing the need for human interaction in healthcare. Our findings advocate for a model where AI augments the diagnostic process, underlining the necessity for educational efforts to mitigate concerns and enhance patient trust in AI-enhanced diagnostics. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
19 pages, 375 KiB  
Review
Breast Cancer Exposomics
by Anca-Narcisa Neagu, Taniya Jayaweera, Lilian Corrice, Kaya Johnson and Costel C. Darie
Life 2024, 14(3), 402; https://doi.org/10.3390/life14030402 - 18 Mar 2024
Viewed by 1181
Abstract
We are exposed to a mixture of environmental man-made and natural xenobiotics. We experience a wide spectrum of environmental exposure in our lifetime, including the effects of xenobiotics on gametogenesis and gametes that undergo fertilization as the starting point of individual development and, [...] Read more.
We are exposed to a mixture of environmental man-made and natural xenobiotics. We experience a wide spectrum of environmental exposure in our lifetime, including the effects of xenobiotics on gametogenesis and gametes that undergo fertilization as the starting point of individual development and, moreover, in utero exposure, which can itself cause the first somatic or germline mutation necessary for breast cancer (BC) initiation. Most xenobiotics are metabolized or/and bioaccumulate and biomagnify in our tissues and cells, including breast tissues, so the xenobiotic metabolism plays an important role in BC initiation and progression. Many considerations necessitate a more valuable explanation regarding the molecular mechanisms of action of xenobiotics which act as genotoxic and epigenetic carcinogens. Thus, exposomics and the exposome concept are based on the diversity and range of exposures to physical factors, synthetic chemicals, dietary components, and psychosocial stressors, as well as their associated biologic processes and molecular pathways. Existing evidence for BC risk (BCR) suggests that food-borne chemical carcinogens, air pollution, ionizing radiation, and socioeconomic status are closely related to breast carcinogenesis. The aim of this review was to depict the dynamics and kinetics of several xenobiotics involved in BC development, emphasizing the role of new omics fields related to BC exposomics, such as environmental toxicogenomics, epigenomics and interactomics, metagenomics, nutrigenomics, nutriproteomics, and nutrimiRomics. We are mainly focused on food and nutrition, as well as endocrine-disrupting chemicals (EDCs), involved in BC development. Overall, cell and tissue accumulation and xenobiotic metabolism or biotransformation can lead to modifications in breast tissue composition and breast cell morphology, DNA damage and genomic instability, epimutations, RNA-mediated and extracellular vesicle effects, aberrant blood methylation, stimulation of epithelial–mesenchymal transition (EMT), disruption of cell–cell junctions, reorganization of the actin cytoskeleton, metabolic reprogramming, and overexpression of mesenchymal genes. Moreover, the metabolism of xenobiotics into BC cells impacts almost all known carcinogenic pathways. Conversely, in our food, there are many bioactive compounds with anti-cancer potential, exerting pro-apoptotic roles, inhibiting cell cycle progression and proliferation, migration, invasion, DNA damage, and cell stress conditions. We can conclude that exposomics has a high potential to demonstrate how environmental exposure to xenobiotics acts as a double-edged sword, promoting or suppressing tumorigenesis in BC. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
16 pages, 1845 KiB  
Review
Breast Reconstruction following Mastectomy for Breast Cancer or Prophylactic Mastectomy: Therapeutic Options and Results
by Laurentiu Simion, Ina Petrescu, Elena Chitoran, Vlad Rotaru, Ciprian Cirimbei, Sinziana-Octavia Ionescu, Daniela-Cristina Stefan, Dan Luca, Dana Lucia Stanculeanu, Adelina Silvana Gheorghe, Horia Doran and Ioana Mihaela Dogaru
Life 2024, 14(1), 138; https://doi.org/10.3390/life14010138 - 18 Jan 2024
Viewed by 1300
Abstract
(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in [...] Read more.
(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in age-standardized breast cancer mortality and have also witnessed a reduction in the medium age at diagnosis, which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we have seen a marked trend toward mastectomies in breast-conserving surgery-eligible patients. Prophylactic mastectomies have also registered an upward trend. This trend together with new uses for breast reconstruction like chest feminization in transgender patients has increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results, and their safety profiles when used during the integrated treatment plan of the oncologic patient. (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures; summarized the findings; and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers, and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the “gold standard”, but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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26 pages, 3132 KiB  
Review
Molecular, Cellular, and Technical Aspects of Breast Cancer Cell Lines as a Foundational Tool in Cancer Research
by Brittany L. Witt and Trygve O. Tollefsbol
Life 2023, 13(12), 2311; https://doi.org/10.3390/life13122311 - 08 Dec 2023
Cited by 2 | Viewed by 2159
Abstract
Breast cancer comprises about 30% of all new female cancers each year and is the most common malignant cancer in women in the United States. Breast cancer cell lines have been harnessed for many years as a foundation for in vitro analytic studies [...] Read more.
Breast cancer comprises about 30% of all new female cancers each year and is the most common malignant cancer in women in the United States. Breast cancer cell lines have been harnessed for many years as a foundation for in vitro analytic studies to understand the use of cancer prevention and therapy. There has yet to be a compilation of works to analyze the pitfalls, novel discoveries, and essential techniques for breast cancer cell line studies in a scientific context. In this article, we review the history of breast cancer cell lines and their origins, as well as analyze the molecular pathways that pharmaceutical drugs apply to breast cancer cell lines in vitro and in vivo. Controversies regarding the origins of certain breast cancer cell lines, the benefits of utilizing Patient-Derived Xenograft (PDX) versus Cell-Derived Xenograft (CDX), and 2D versus 3D cell culturing techniques will be analyzed. Novel outcomes from epigenetic discovery with dietary compound usage are also discussed. This review is intended to create a foundational tool that will aid investigators when choosing a breast cancer cell line to use in multiple expanding areas such as epigenetic discovery, xenograft experimentation, and cancer prevention, among other areas. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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12 pages, 9597 KiB  
Review
Progress and Challenges of Immunotherapy Predictive Biomarkers for Triple Negative Breast Cancer in the Era of Single-Cell Multi-Omics
by Jiangnan Yu, Zhikun Guo and Lei Wang
Life 2023, 13(5), 1189; https://doi.org/10.3390/life13051189 - 16 May 2023
Cited by 5 | Viewed by 3113
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with a poor prognosis. Despite conventional treatments, including surgery, radiation, and chemotherapy, the overall response rate to PD-1/PD-L1 immune checkpoint inhibitors remains low, with limited predictive significance from current biomarkers such [...] Read more.
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with a poor prognosis. Despite conventional treatments, including surgery, radiation, and chemotherapy, the overall response rate to PD-1/PD-L1 immune checkpoint inhibitors remains low, with limited predictive significance from current biomarkers such as PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and tumor mutational burden (TMB). To address this challenge, recent advancements in single-cell sequencing techniques have enabled deeper exploration of the highly complex and heterogeneous TNBC tumor microenvironment at the single-cell level, revealing promising TNBC predictive biomarkers for immune checkpoint inhibitors. In this review, we discuss the background, motivation, methodology, results, findings, and conclusion of multi-omics analyses that have led to the identification of these emerging biomarkers. Our review suggests that single-cell multi-omics analysis holds great promise for the identification of more effective biomarkers and personalized treatment strategies for TNBC patients. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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Other

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13 pages, 1966 KiB  
Systematic Review
Adverse Events of PD-1 or PD-L1 Inhibitors in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis
by Yixi Zhang, Jingyuan Wang, Taobo Hu, Huina Wang, Mengping Long and Baosheng Liang
Life 2022, 12(12), 1990; https://doi.org/10.3390/life12121990 - 28 Nov 2022
Cited by 7 | Viewed by 1965
Abstract
(1) Background: This study aimed to develop a comprehensive understanding of the treatment-related adverse events when using PD-1 or PD-L1 inhibitors in triple-negative breast cancer (TNBC). (2) Methods: We conducted a meta-analysis of Phase II/III randomized clinical trials. Studies were searched for using [...] Read more.
(1) Background: This study aimed to develop a comprehensive understanding of the treatment-related adverse events when using PD-1 or PD-L1 inhibitors in triple-negative breast cancer (TNBC). (2) Methods: We conducted a meta-analysis of Phase II/III randomized clinical trials. Studies were searched for using PubMed, Embase, and Cochrane Library from 1 March 1980 till 30 June 2022. Data on adverse events were mainly extracted from ClinicalTrials.gov and published articles. A generalized linear mixed model with the logit transformation was employed to obtain the overall incidence of adverse events across all studies. For serious adverse events with low incidences, the Peto method was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) in the PD-1 or PD-L1 inhibitors groups compared to the control groups. (3) Results: Nine studies were included in the meta-analysis, including a total of 2941 TNBC patients treated with PD-1 or PD-L1 inhibitors (including atezolizumab, pembrolizumab and durvalumab) and 2339 patients in the control groups. Chemotherapy alone was the control group in all studies. The average incidences of all serious immune-related adverse events of interest (hypothyroidism, hyperthyroidism, pneumonitis, pruritus, rash) were less than 1%, except for adrenal insufficiency (1.70%, 95%CI: 0.50–5.61%) in the PD-1 or PD-L1 groups. PD-1 or PD-L1 inhibitors significantly increased the risk of serious pneumonitis (OR = 2.52, 95%CI: 1.02–6.26), hypothyroidism (OR = 5.92, 95%CI: 1.22–28.86), alanine aminotransferase (ALT) elevation (OR = 1.66, 95%CI: 1.12–2.45), and adrenal insufficiency (OR = 18.81, 95%CI: 3.42–103.40). For non-serious adverse events, the patients treated with PD-1 or PD-L1 inhibitors had higher risk of aspartate aminotransferase (AST) elevation (OR =1.26, 95%CI: 1.02–1.57), hypothyroidism (OR = 3.63, 95%CI: 2.92–4.51), pruritus (OR = 1.84, 95%CI: 1.30–2.59), rash (OR = 1.29, 95%CI: 1.08–1.55), and fever (OR = 1.77, 95%CI: 1.13–2.77), compared with chemotherapy alone. (4) Conclusions: The incidence of serious immune-related adverse events in PD-1 or PD-L1 inhibitors groups is low but significantly higher than in chemotherapy groups. When using PD-1 or PD-L1 inhibitors for the treatment of TNBC, serious pneumonitis, hypothyroidism, ALT elevation, and adrenal insufficiency should be considered. Non-serious adverse events, such as AST elevation, rash, and fever, should also be taken into consideration. Full article
(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)
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