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21 pages, 181343 KiB

Open AccessArticle

Improved Breast Cancer Classification through Combining Transfer Learning and Attention Mechanism

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Asadulla Ashurov

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Samia Allaoua Chelloug

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Alexey Tselykh

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Mohammed Saleh Ali Muthanna

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Ammar Muthanna

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Mehdhar S. A. M. Al-Gaashani

Life 2023, 13(9), 1945; https://doi.org/10.3390/life13091945 - 21 Sep 2023

Viewed by 647

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

Open AccessArticle

The Role of Diffusion-Weighted Imaging Based on Maximum-Intensity Projection in Young Patients with Marked Background Parenchymal Enhancement on Contrast-Enhanced Breast MRI

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Life 2023, 13(8), 1744; https://doi.org/10.3390/life13081744 - 14 Aug 2023

Viewed by 541

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

Open AccessArticle

Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer

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Life 2023, 13(4), 998; https://doi.org/10.3390/life13040998 - 12 Apr 2023

Viewed by 1401

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

Open AccessArticle

Clinicopathological Characteristics and Prognostic Profiles of Breast Carcinoma with Neuroendocrine Features

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Life 2023, 13(2), 532; https://doi.org/10.3390/life13020532 - 15 Feb 2023

Cited by 1 | Viewed by 853

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

Open AccessArticle

In Silico Analysis of Publicly Available Transcriptomic Data for the Identification of Triple-Negative Breast Cancer-Specific Biomarkers

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Life 2023, 13(2), 422; https://doi.org/10.3390/life13020422 - 02 Feb 2023

Cited by 2 | Viewed by 1770

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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11 pages, 1390 KiB

Open AccessArticle

Biomarker Alteration after Neoadjuvant Endocrine Therapy or Chemotherapy in Estrogen Receptor-Positive Breast Cancer

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Life 2023, 13(1), 74; https://doi.org/10.3390/life13010074 - 27 Dec 2022

Cited by 2 | Viewed by 1628

Abstract

In estrogen receptor (ER)-positive breast cancer, changes in biomarker expression after neoadjuvant therapy indicate the therapeutic response and are prognostic. However, there is limited information about the biomarker alteration caused by neoadjuvant endocrine therapy in ER-positive and human epidermal growth factor receptor 2 [...] Read more.

In estrogen receptor (ER)-positive breast cancer, changes in biomarker expression after neoadjuvant therapy indicate the therapeutic response and are prognostic. However, there is limited information about the biomarker alteration caused by neoadjuvant endocrine therapy in ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We recruited ER-positive/HER2-negative breast cancer patients who received neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET), or sequential neoadjuvant endocrine-chemotherapy (NECT) at Peking University Cancer Hospital from 2015 to 2021. A total of 579 patients had paired immunohistochemistry information in both diagnostic biopsy samples and post-neoadjuvant therapy surgical samples. Through a paired comparison of the immunohistochemical information in pre-treatment and post-treatment samples, we found that progesterone receptor (PR) expression reductions were more frequent than ER expression reductions (70.8% vs. 35.2%) after neoadjuvant therapy. The percentage of patients who had a decreased Ki-67 index in the post-operative samples was similar in the three groups (79.8% vs. 79.7% vs. 78.4%). Moreover, PR losses caused by NET were related to low baseline PR expression (p = 0.001), while we did not find a significant association between PR losses and Ki-67 reductions (p = 0.428) or ER losses (p = 0.274). All three types of neoadjuvant therapies caused a reduction in ER, PR, and Ki-67 expression. In conclusion, we found that PR loss after NET was only significantly related to low baseline PR expression, and there is no significant difference in the extent of prognostic factor change including Ki-67 and ER between the PR loss and non-loss groups. 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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12 pages, 9597 KiB

Open AccessReview

Progress and Challenges of Immunotherapy Predictive Biomarkers for Triple Negative Breast Cancer in the Era of Single-Cell Multi-Omics

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Jiangnan Yu

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Zhikun Guo

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Lei Wang

Life 2023, 13(5), 1189; https://doi.org/10.3390/life13051189 - 16 May 2023

Cited by 3 | Viewed by 2007

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

Open AccessSystematic Review

Adverse Events of PD-1 or PD-L1 Inhibitors in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

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Life 2022, 12(12), 1990; https://doi.org/10.3390/life12121990 - 28 Nov 2022

Cited by 2 | Viewed by 1582

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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