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Current Use and Perspectives of Molecular Assessment in Breast Cancer
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Current Use and Perspectives of Molecular Assessment in Breast Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 12131

Special Issue Editors

Dr. Patrizia Vici

E-Mail Website
Guest Editor
IRCCS Regina Elena National Cancer Institute, Roma, Italy
Interests: breast neoplasms; mammary cancer; breast cancer molecular assessement; breast cancer molecular diagnostics
Dr. Maddalena Barba

E-Mail Website
Guest Editor
Medical Oncology Division2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
Interests: breast neoplasms; mammary cancer; breast cancer molecular assessment; breast cancer molecular diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

In the last few decades, the role of molecular assessment techniques in breast cancer has deeply changed.

The goals achieved and fields of application have now become virtually unlimited.

Prognosis definition deserves a mention, along with the potential held in informing decision-making processes and treatment administration across different breast cancer settings.

Within such an interesting frame, a specific focus will be on the following subtopics: 

  1. Early disease;
  2. Locally advanced/metastatic disease;
  3. Molecular assessment combined with groundbreaking techniques in the discovery/validation phase of breast cancer prognostic/predictive biomarkers;
  4. The bridging role of molecular assessment between the preclinical and clinical setting.

We welcome submissions of original research papers and reviews on this topic of interest, with a highlight on molecular research and findings.

Dr. Patrizia Vici
Dr. Maddalena Barba
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

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Research

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15 pages, 6951 KiB  
Article
Identification of a Gene Panel Predictive of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy Employing Transcriptomic and Functional Validation
by Radhakrishnan Vishnubalaji, Hikmat Abdel-Razeq, Salahddin Gehani, Omar M. E. Albagha and Nehad M. Alajez
Int. J. Mol. Sci. 2022, 23(18), 10901; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810901 - 17 Sep 2022
Cited by 9 | Viewed by 2262
Abstract
Triple-negative breast cancer (TNBC) patients exhibiting pathological complete response (pCR) have better clinical outcomes compared to those with residual disease (RD). Therefore, robust biomarkers that can predict pCR may help with triage and resource prioritization in patients with TNBC. Herein, we identified a [...] Read more.
Triple-negative breast cancer (TNBC) patients exhibiting pathological complete response (pCR) have better clinical outcomes compared to those with residual disease (RD). Therefore, robust biomarkers that can predict pCR may help with triage and resource prioritization in patients with TNBC. Herein, we identified a gene panel predictive of RD and pCR in TNBC from the discovery (n = 90) treatment-naive tumor transcriptomic data. Eight RD-derived genes were identified as TNBC-essential genes, which were highly predicative of overall survival (OS) and relapse-free survival (RFS) in an additional cohort of basal breast cancer (n = 442). Mechanistically, targeted depletion of the eight genes reduced the proliferation potential of TNBC cell models, while most remarkable effects were for combined SLC39A7, TIMM13, BANF1, and MVD knockdown in conjunction with doxorubicin. Orthogonal partial least squares-discriminant analysis (OPLS-DA) and receiver operating characteristic curve (ROC) analyses revealed significant predictive power for the identified gene panels with an area under the curve (AUC) of 0.75 for the validation cohort (n = 50) to discriminate RD from pCR. Protein–Protein Interaction (PPI) network analysis of the pCR-derived gene signature identified an 87-immune gene signature highly predictive of pCR, which correlated with better OS, RFS, and distant-metastasis-free survival (DMFS) in an independent cohort of basal and, to a lesser extent, HER2+ breast cancer. Our data have identified gene signatures predicative of RD and pCR in TNBC with potential clinical implications. Full article
(This article belongs to the Special Issue Current Use and Perspectives of Molecular Assessment in Breast Cancer)
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16 pages, 7633 KiB  
Article
Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
by Marta Dratwa, Barbara Wysoczanska, Wioletta Brankiewicz, Martyna Stachowicz-Suhs, Joanna Wietrzyk, Rafał Matkowski, Marcin Ekiert, Jolanta Szelachowska, Adam Maciejczyk, Mariusz Szajewski, Maciej Baginski and Katarzyna Bogunia-Kubik
Int. J. Mol. Sci. 2022, 23(9), 5164; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095164 - 05 May 2022
Cited by 9 | Viewed by 2174
Abstract
The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC [...] Read more.
The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness. Full article
(This article belongs to the Special Issue Current Use and Perspectives of Molecular Assessment in Breast Cancer)
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11 pages, 2959 KiB  
Article
Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib, Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment
by Michele Iuliani, Sonia Simonetti, Giulia Ribelli, Andrea Napolitano, Umile Giuseppe Longo, Bruno Vincenzi, Paolo Orsaria, Vincenzo Denaro, Giuseppe Tonini, Daniele Santini and Francesco Pantano
Int. J. Mol. Sci. 2022, 23(5), 2477; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052477 - 24 Feb 2022
Cited by 6 | Viewed by 2595
Abstract
The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the [...] Read more.
The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice. Full article
(This article belongs to the Special Issue Current Use and Perspectives of Molecular Assessment in Breast Cancer)
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Review

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16 pages, 933 KiB  
Review
Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration
by Eriseld Krasniqi, Frauke Goeman, Claudio Pulito, Alina Catalina Palcau, Ludovica Ciuffreda, Francesca Sofia Di Lisa, Lorena Filomeno, Maddalena Barba, Laura Pizzuti, Federico Cappuzzo, Giuseppe Sanguineti, Marcello Maugeri-Saccà, Gennaro Ciliberto, Maurizio Fanciulli, Giovanni Blandino and Patrizia Vici
Int. J. Mol. Sci. 2022, 23(23), 14534; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314534 - 22 Nov 2022
Cited by 3 | Viewed by 2573
Abstract
New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, [...] Read more.
New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, approximately 10% of tumors show primary resistance, whereas acquired resistance appears to be an almost ubiquitous occurrence, leading to treatment failure. The identification of differentially expressed genes or genomic mutational signatures able to predict sensitivity or resistance to CDK4/6 inhibitors is critical for medical decision making and for avoiding or counteracting primary or acquired resistance against CDK4/6 inhibitors. In this review, we summarize the main mechanisms of resistance to CDK4/6 inhibitors, focusing on those associated with potentially relevant biomarkers that could predict patients’ response/resistance to treatment. Recent advances in biomarker identification are discussed, including the potential use of liquid biopsy for BC management and the role of multiple microRNAs as molecular predictors of cancer cell sensitivity and resistance to CDK4/6 inhibitors. Full article
(This article belongs to the Special Issue Current Use and Perspectives of Molecular Assessment in Breast Cancer)
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11 pages, 438 KiB  
Review
Role of Intrinsic Subtype Analysis with PAM50 in Hormone Receptors Positive HER2 Negative Metastatic Breast Cancer: A Systematic Review
by Fabio Canino, Federico Piacentini, Claudia Omarini, Angela Toss, Monica Barbolini, Patrizia Vici, Massimo Dominici and Luca Moscetti
Int. J. Mol. Sci. 2022, 23(13), 7079; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137079 - 25 Jun 2022
Cited by 4 | Viewed by 1937
Abstract
Endocrine therapy (ET), associated with CDK 4/6 inhibitors, represents the first choice of treatment for HR+/HER2- metastatic breast cancer (mBC). Primary or secondary endocrine resistance could develop; however validated biomarkers capable of predicting such a conditions are not available. Several studies have shown [...] Read more.
Endocrine therapy (ET), associated with CDK 4/6 inhibitors, represents the first choice of treatment for HR+/HER2- metastatic breast cancer (mBC). Primary or secondary endocrine resistance could develop; however validated biomarkers capable of predicting such a conditions are not available. Several studies have shown that HR+/HER2- mBC comprises five intrinsic subtypes. The purpose of this systematic review was to analyze the potential correlations between intrinsic subtype, efficacy of treatment, and patient outcome. Five papers that analyzed the intrinsic subtype with PAM50 assay in patients (pts) with HR+/HER2- mBC treated with ET (alone or in combination) within seven phase III clinical trials (EGF30008, BOLERO-2, PALOMA-2,3, MONALEESA-2,3,7) were identified. Non-luminal subtypes are more frequent in endocrine-resistant pts and in metastatic sites (vs. primary tumors), have less benefit from ET, and worse prognosis. Among these, HER2-enriched subtypes are similar to HER2+ tumors and benefit from the addition of anti-HER2 agents (lapatinib) and, for less clear reasons, of ribociclib (unconfirmed data for palbociclib and everolimus). Basal-like subtypes are similar to triple-negative tumors, making them more sensitive to chemotherapy. The intrinsic subtype is also not static but can vary over time with the evolution of the disease. Currently, the intrinsic subtype does not play a decisive role in the choice of treatment in clinical practice, but has potential prognostic and predictive value that should be further investigated. Full article
(This article belongs to the Special Issue Current Use and Perspectives of Molecular Assessment in Breast Cancer)
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