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Identification of New Molecular Subgroups in Breast Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 5950

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Dipartimento di Patologia Umana Dell’adulto e Dell’età Evolutiva Gaetano Barresi, Divisione di Anatomia Patologica, Università Degli Studi di Messina, 98125 Messina, Italy
Interests: autophagy; molecular biology; pathology; innate immunity; gastritis; Helicobacter pylori; neutrophils; mast cell
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Special Issue Information

Dear Colleagues,

Molecular testing is assuming an increasingly central role in neoplastic breast pathology, where it can guide adequate treatment approaches by providing valuable diagnostic information and aiding physicians in the clinical management. In fact, breast cancer is a complex disease with significant molecular heterogeneity, and various molecular subgroups have been identified in recent years. Several studies based on gene expression profiles have contributed to the identification of such molecularly distinct entities, and specific single-nucleotide variants have been detected in different cancer subtypes. These findings contribute to a better understanding of breast cancer's molecular heterogeneity and may have implications for prognosis and targeted therapies. Furthermore, advances in high-throughput genomic profiling have resulted in the development of a genome-driven integrated classification of breast cancer, which refines the existing classification systems and sheds light on the underlying biology and potential molecular drivers. Overall, the discovery of new molecular subgroups in breast cancer may lead to better personalized treatment strategies by increasing our understanding of the disease. Therefore, this Special Issue's goal is to explore all areas of research based on the molecular characterization of breast cancer, including the identification of new molecular subgroups that can improve breast cancer classification and treatment. It will include original research, review articles, and short communications on molecular mechanisms implicated in breast cancer pathology and their potential therapeutic implications.

Dr. Vincenzo Fiorentino
Prof. Dr. Giovanni Tuccari
Guest Editors

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Keywords

  • breast cancer
  • molecular subgroups
  • gene expression profiles
  • molecular tests
  • targeted agents

Published Papers (3 papers)

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Research

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14 pages, 880 KiB  
Article
The Predictive Role of Serum Lipid Levels, p53 and ki-67, According to Molecular Subtypes in Breast Cancer: A Randomized Clinical Study
by Ionut Flaviu Faur, Amadeus Dobrescu, Ioana Adelina Clim, Paul Pasca, Catalin Prodan-Barbulescu, Cristi Tarta, Andreea-Adriana Neamtu, Dan Brebu, Carmen Neamtu, Mihai Rosu, Ciprian Duta, Andreea Clim, Gabriel Lazar and Bogdan Totolici
Int. J. Mol. Sci. 2024, 25(7), 3911; https://doi.org/10.3390/ijms25073911 - 31 Mar 2024
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Abstract
Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a [...] Read more.
Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) (p < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume (p = 0.002) and increased level of HDL (p = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS. Full article
(This article belongs to the Special Issue Identification of New Molecular Subgroups in Breast Cancer)
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15 pages, 2018 KiB  
Article
The Interaction of the Endocannabinoid Anandamide and Paracannabinoid Lysophosphatidylinositol during Cell Death Induction in Human Breast Cancer Cells
by Mikhail G. Akimov, Natalia M. Gretskaya, Evgenia I. Gorbacheva, Nisreen Khadour, Valeria S. Chernavskaya, Galina D. Sherstyanykh, Tatiana F. Kovaleko, Elena V. Fomina-Ageeva and Vladimir V. Bezuglov
Int. J. Mol. Sci. 2024, 25(4), 2271; https://doi.org/10.3390/ijms25042271 - 14 Feb 2024
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Abstract
Endocannabinoid anandamide (AEA) and paracannabinoid lysophosphatidylinositol (LPI) play a significant role in cancer cell proliferation regulation. While anandamide inhibits the proliferation of cancer cells, LPI is known as a cancer stimulant. Despite the known endocannabinoid receptor crosstalk and simultaneous presence in the cancer [...] Read more.
Endocannabinoid anandamide (AEA) and paracannabinoid lysophosphatidylinositol (LPI) play a significant role in cancer cell proliferation regulation. While anandamide inhibits the proliferation of cancer cells, LPI is known as a cancer stimulant. Despite the known endocannabinoid receptor crosstalk and simultaneous presence in the cancer microenvironment of both molecules, their combined activity has never been studied. We evaluated the effect of LPI on the AEA activity in six human breast cancer cell lines of different carcinogenicity (MCF-10A, MCF-7, BT-474, BT-20, SK-BR-3, MDA-MB-231) using resazurin and LDH tests after a 72 h incubation. AEA exerted both anti-proliferative and cytotoxic activity with EC50 in the range from 31 to 80 µM. LPI did not significantly affect the cell viability. Depending on the cell line, the response to the LPI–AEA combination varied from a decrease in AEA cytotoxicity to an increase in it. Based on the inhibitor analysis of the endocannabinoid receptor panel, we showed that for the former effect, an active GPR18 receptor was required and for the latter, an active CB2 receptor. The data obtained for the first time are important for the understanding the manner by which endocannabinoid receptor ligands acting simultaneously can modulate cancer growth at different stages. Full article
(This article belongs to the Special Issue Identification of New Molecular Subgroups in Breast Cancer)
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Review

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14 pages, 729 KiB  
Review
Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes
by Mariausilia Franchina, Cristina Pizzimenti, Vincenzo Fiorentino, Maurizio Martini, Giuseppina Rosaria Rita Ricciardi, Nicola Silvestris, Antonio Ieni and Giovanni Tuccari
Int. J. Mol. Sci. 2023, 24(16), 12795; https://doi.org/10.3390/ijms241612795 - 14 Aug 2023
Cited by 1 | Viewed by 3002
Abstract
HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed [...] Read more.
HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed to exactly distinguish HER2-low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody–drug conjugates (ADCs) in treating these groups of tumors. In particular, trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC, has been recently approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06 trial, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally, we hope that new guidelines may help to codify HER2-low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment. Full article
(This article belongs to the Special Issue Identification of New Molecular Subgroups in Breast Cancer)
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