Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments

Medical Sciences, Journal Year: 2020, Volume and Issue: 8(1), P. 18 - 18

Published: March 23, 2020

Breast cancer is the most commonly occurring in women. There were over two-million new cases world 2018. It second leading cause of death from western countries. At molecular level, breast a heterogeneous disease, which characterized by high genomic instability evidenced somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The caused defects DNA damage repair, transcription, replication, telomere maintenance mitotic segregation. According to features, cancers are subdivided subtypes, according activation hormone receptors (estrogen receptor progesterone receptor), human epidermal growth factors 2 (HER2), or BRCA mutations. In-depth analyses features primary metastatic have shown great heterogeneity genetic alterations their clonal evolution during disease development. These studies contributed identify repertoire numerous disease-causing genes that altered through different mutational processes. While early-stage curable about 70% patients, advanced largely incurable. However, develop therapeutic approaches targeting HER2, CDK4/6, PI3K, involving poly(ADP-ribose) polymerase inhibitors for mutation carriers immunotherapy.

Language: Английский

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Polygenic risk scores and breast cancer risk prediction

The Breast, Journal Year: 2023, Volume and Issue: 67, P. 71 - 77

Published: Jan. 10, 2023

Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have the potential to improve screening prevention strategies. PRS combine from Single nucleotide polymorphisms (SNPs) associated with in Genome Wide Association Studies (GWAS) explain over 30% heritability. When incorporated into models, more personalised assessment derived PRS, help identify women at higher development enables implementation stratified approaches. This review describes role including their clinical application. We also examined within well-established models which incorporate known classic factors discuss interaction these capacity predict subtypes. Before can be implemented on population-wide scale, there several challenges that must addressed. Perhaps most pressing is use non-White European origin, where been shown attenuated both discrimination calibration. progress developing applying non-white populations. represent significant advance further will undoubtedly enhance personalisation.

Language: Английский

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From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

Frontiers in Veterinary Science, Journal Year: 2021, Volume and Issue: 8

Published: Feb. 17, 2021

Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. cancer (CMC) represents 50% of CMTs, and besides surgery, which is elective treatment, additional targeted non-targeted therapies could offer benefits terms survival to these patients. Also, CMC considered a good spontaneous intermediate animal model for research human breast (HBC), therefore, study new treatments promising field comparative oncology. Dogs with have comparable disease, an immune system, much shorter life span, allows achievement results relatively short time. Besides conventional chemotherapy, innovative large niche opportunities. In this article, comprehensive review current adjuvant conducted gather available information evaluate perspectives. Firstly, updates provided on clinical–pathological approach use therapies, delve later into precision against therapeutic targets such as hormone receptors, tyrosine kinase p 53 tumor suppressor gene, cyclooxygenases, signaling pathways involved epithelial–mesenchymal transition, immunotherapy different approaches. A comparison investigations HBC also carried out. last years, increasing number basic studies agents cell lines mouse xenografts outstanding. As main conclusion review, lack effort bring vitro applied clinical emerges. There great need well-planned prospective randomized trials dogs obtain valid both species, humans dogs, therapies. Following One Health concept, veterinary oncology will join forces take advantage economic technological resources that invested research, together innumerable advantages model.

Language: Английский

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Oncogenic and Tumor Suppressive Components of the Cell Cycle in Breast Cancer Progression and Prognosis

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(4), P. 569 - 569

Published: April 17, 2021

Cancer, a disease of inappropriate cell proliferation, is strongly interconnected with the cycle. All cancers consist an abnormal accumulation neoplastic cells, which are propagated toward uncontrolled division and proliferation in response to mitogenic signals. Mitogenic stimuli include genetic epigenetic changes cycle regulatory genes other regulate This suggests that multiple, distinct pathways alterations lead cancer development. Products both oncogenes (including cyclin-dependent kinase (CDKs) cyclins) tumor suppressor inhibitors) machinery promote or suppress progression, respectively. The identification cyclins CDKs help explain understand molecular mechanisms machinery. During breast tumorigenesis, A, B, C, D1, E; (CDKs); CDK-inhibitor proteins p16, p21, p27, p53 known play significant roles control tightly regulated normal epithelial cells. Following stimuli, these components deregulated, promotes transformation Multiple studies implicate types components—oncogenic cyclins, along tumor-suppressing inhibitors—in initiation progression. Numerous clinical have confirmed there prognostic significance for screening described components, regarding patient outcomes their responses therapy. aim this review article summarize oncogenic tumor-suppressive progression prognosis.

Language: Английский

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Development and testing of a random forest-based machine learning model for predicting events among breast cancer patients with a poor response to neoadjuvant chemotherapy

European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)

Published: Sept. 30, 2023

Breast cancer (BC) is the most common malignant tumor around world. Timely detection of progression after treatment could improve survival outcome patients. This study aimed to develop machine learning models predict events (defined as either (1) first relapse locally, regionally, or distantly; (2) a diagnosis secondary tumor; (3) death because any reason.) in BC patients post-treatment.The with response stable disease (SD) and progressive (PD) neoadjuvant chemotherapy (NAC) were selected. The clinicopathological features data recorded 1 year 5 years, respectively. Patients randomly divided into training set test ratio 8:2. A random forest (RF) logistic regression established both 1-year cohort 5-year cohort. performance was compared between two models. validated using from Surveillance, Epidemiology, End Results (SEER) database.A total 315 included. In cohort, 197 while 87 set. specificity, sensitivity, AUC 0.800, 0.833, 0.810 RF model. And 0.520, 0.653 regression. 132 33 0.882, 0.750, 0.829 0.688, 0.752 external validation set, model, 0.765, 0.812, 0.779. Of logistics 0.376, 0.619.The model has good predicting among SD PD post-NAC. It may be beneficial patients, assisting detecting recurrence.

Language: Английский

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Clinicopathological and epidemiological significance of breast cancer subtype reclassification based on p53 immunohistochemical expression

npj Breast Cancer, Journal Year: 2019, Volume and Issue: 5(1)

Published: July 25, 2019

Abstract TP53 mutations are common in breast cancer and typically associated with more aggressive tumor characteristics, but little is known about the clinicopathological epidemiological relevance of p53 protein expression, a mutation surrogate, subtypes. In this study 7226 Chinese women invasive cancer, we defined subtypes using immunohistochemical (IHC) measures hormone receptors HER2 conjunction histologic grade. expression status was then used to further stratify into p53-positive p53-negative. Odds ratios (ORs) 95% confidence intervals (CIs) case-only logistic regression analyses were examine heterogeneity across different The frequency varied by subtype, being lowest luminal A-like highest triple-negative HER2-enriched ( P -value < 0.01). B-like/HER2-negative subtypes, positivity early-onset tumors, high grade, proliferative index, basal marker (CK5/6 EGFR) expression. Further, compared A-like/p53-negative patients, A-like/p53-positive patients likely be parous [adjusted OR vs. nulliparous = 2.67 (1.60, 4.51); 0.01] have breastfed ever never 1.38 (1.03, 1.85); 0.03]. not examined clinical risk factors other Overall, these findings suggest that which readily available many settings, can identify phenotypes distinct implications.

Language: Английский

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Risk factors for breast cancer subtypes by race and ethnicity: a scoping review

JNCI Journal of the National Cancer Institute, Journal Year: 2024, Volume and Issue: 116(12), P. 1992 - 2002

Published: July 16, 2024

Breast cancer consists of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated.

Language: Английский

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Endocrine resistance and breast cancer plasticity are controlled by CoREST

Nature Structural & Molecular Biology, Journal Year: 2022, Volume and Issue: 29(11), P. 1122 - 1135

Published: Nov. 1, 2022

Language: Английский

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Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations

Human Genomics, Journal Year: 2023, Volume and Issue: 17(1)

Published: Jan. 6, 2023

Germline mutations of breast cancer susceptibility gene BRCA1 and BRCA2 (gBRCA1/2) are associated with elevated risk in young women Asia. proteins contribute to genomic stability through homologous recombination (HR)-mediated double-strand DNA break repair cooperation other HR-related proteins. In this study, we analyzed the targeted sequencing data Korean patients gBRCA1/2 investigate alterations genes their clinical implications.

Language: Английский

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The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13165 - 13165

Published: Dec. 7, 2024

Breast cancer is a significant health challenge worldwide and the most frequently diagnosed among women globally. This review provides comprehensive overview of breast biology, genomics, microbial dysbiosis, focusing on its various subtypes racial differences. primarily classified into carcinomas sarcomas, with constituting cases. Epidemiology risk factors are important for public intervention. Staging grading, based TNM Nottingham grading systems, respectively, crucial to determining clinical outcome treatment decisions. Histopathological include in situ invasive carcinomas, such as ductal carcinoma (IDC) lobular (ILC). The explores molecular subtypes, including Luminal A, B, Basal-like (Triple Negative), HER2-enriched, delves cancer's histological progression patterns. Recent research findings related nuclear mitochondrial genetic alterations, epigenetic reprogramming, role microbiome dysbiosis differences also reported. an update current diagnostics modalities.

Language: Английский

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