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Cancers
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Biomarkers in HER2 Positive Breast Cancer
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Biomarkers in HER2 Positive Breast Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (20 November 2022) | Viewed by 7281

Special Issue Editor

Prof. Dr. Christian Singer

E-Mail Website
Guest Editor
Department of Obstretrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
Interests: breast cancer; translational research; clinical trials; hereditary breast and ovarian cancer; gynecological oncology; chemotherapy; targeted therapy; BRCA1; BRCA2

Special Issue Information

Dear Colleagues,

Breast cancer is the most common female malignancy in the industrialized world, and approximately 20% of women diagnosed with early breast cancer present with tumors that are characterized by HER2/neu amplification. While the associated Her-2/neu receptor overexpression results in a high risk of relapse and poor prognosis, it also defines a target for antibody therapies and small molecules that interfere with HER2-associated signal transduction. HER2-directed therapies have profoundly improved long-term outcome, but they are also burdened by side effects. Currently available biomarkers such as immunohistochemistry and fluorescence in situ hybridization (FISH) permit identifying patients who do not benefit from HER2-targeted; however, only a proportion of patients considered to be candidates for targeted treatment actually respond.

Consequently, over the last few years, a number of biomarkers have been evaluated for their potential to predict response to trastuzumab-based therapies. These include markers of Her-2/neu activation, but components of Her-2/neu-induced downstream signaling pathways that are crucial for the growth inhibitory effects of trastuzumab Co-amplification of other parameters have also been identified as potentially useful predictors of treatment response, and their use in the clinical setting is currently being evaluated.

For this Special Issue of Cancers, we will welcome manuscripts describing novel data, methods, collaborative initiatives, editorials, and reviews related to the topic of HER2 biomarkers that contribute to improving therapies for HER2 positive breast cancer.

Prof. Dr. Christian Singer
Guest Editor

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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.

Keywords

  • HER2

  • breast cancer
  • biomarker
  • trastuzumab
  • tyrosin-kinase inhibitor
  • response prediction

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Published Papers (2 papers)

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Research

30 pages, 3153 KiB  
Article
Potential Impact of PI3K-AKT Signaling Pathway Genes, KLF-14, MDM4, miRNAs 27a, miRNA-196a Genetic Alterations in the Predisposition and Progression of Breast Cancer Patients
by Othman R. Alzahrani, Rashid Mir, Hanan E. Alatwi, Yousef M. Hawsawi, Amnah A. Alharbi, Abdulrahman H. Alessa, Elham Saleh Albalawi, Imadeldin Elfaki, Yousef Alalawi, Laila Moharam and Sabah H. El-Ghaiesh
Cancers 2023, 15(4), 1281; https://doi.org/10.3390/cancers15041281 - 17 Feb 2023
Cited by 9 | Viewed by 3322
Abstract
Genome-wide association studies have reported link between SNPs and risk of breast cancer. This study investigated the association of the selected gene variants by predicting them as possible target genes. Molecular technique advances with the availability of whole-exome sequencing (WES), now offer opportunities [...] Read more.
Genome-wide association studies have reported link between SNPs and risk of breast cancer. This study investigated the association of the selected gene variants by predicting them as possible target genes. Molecular technique advances with the availability of whole-exome sequencing (WES), now offer opportunities for simultaneous investigations of many genes. The experimental protocol for PI3K, AKT-1, KLF-14, MDM4, miRNAs 27a, and miR-196a genotyping was done by ARMS-PCR and sanger sequencing. The novel and known gene variants were studied by Whole-exome sequencing using Illumina NovaSeq 6000 platform. This case control study reports significant association between BC patients, healthy controls with the polymorphic variants of PI3K C > T, AKT-1 G > A KLF 14 C > T, MDM4 A > G, miR-27a A > G, miR-196a-2 C > T genes (p < 0.05). MDM4 A > G genotypes were strongly associated with BC predisposition with OR 2.08 & 2.15, p < 0.05) in codominant and dominant models respectively. MDM4 A allele show the same effective (OR1.76, p < 0.05) whereas it remains protective in recessive model for BC risk. AKT1G > A genotypes were strongly associated with the BC susceptibility in all genetic models whereas PI3K C > T genotypes were associated with breast cancer predisposition in recessive model OR 6.96. Polymorphic variants of KLF-14 A > G, MDM4G > A, MiR-27aA >G, miR-196a-C > T were strongly associated with stage, tamoxifen treatment. Risk variants have been reported by whole exome sequencing in our BC patients. It was concluded that a strong association between the PI3K-AKT signaling pathway gene variants with the breast cancer susceptibility and progression. Similarly, KLF 14-AA, MDM4-GA, miR27a-GG and miR-196a-CT gene variants were associated with the higher risk probability of BC and were strongly correlated with staging of the BC patients. This study also reported Low, novel, and intermediate-genetic-risk variants of PI3K, AKT-1, MDM4G & KLF-14 by utilizing whole-exome sequencing. These variants should be further investigated in larger cohorts’ studies. Full article
(This article belongs to the Special Issue Biomarkers in HER2 Positive Breast Cancer)
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22 pages, 2736 KiB  
Article
STARD3: A New Biomarker in HER2-Positive Breast Cancer
by Massimo Lodi, Laetitia Voilquin, Fabien Alpy, Sébastien Molière, Nathalie Reix, Carole Mathelin, Marie-Pierrette Chenard and Catherine-Laure Tomasetto
Cancers 2023, 15(2), 362; https://doi.org/10.3390/cancers15020362 - 5 Jan 2023
Cited by 10 | Viewed by 3085
Abstract
Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are [...] Read more.
Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are co-expressed. The STARD3 gene belongs to the HER2 amplicon, and its role as a predictive marker was never addressed. The objective of this study was to investigate the predictive value of STARD3 protein expression on NST pathological response in HER2-positive breast cancer. In addition, we studied the prognostic value of this marker. Methods. We conducted a retrospective study between 2007 and 2020 on 112 patients with non-metastatic HER2-positive breast cancer treated by NST and then by surgery. We developed an immunohistochemistry assay for STARD3 expression and subcellular localization and determined a score for STARD3-positivity. As STARD3 is an endosomal protein, its expression was considered positive if the intracellular signal pattern was granular. Results: In this series, pCR was achieved in half of the patients. STARD3 was positive in 86.6% of cases and was significantly associated with pCR in univariate analysis (p = 0.013) and after adjustment on other known pathological parameters (p = 0.044). Performances on pCR prediction showed high sensitivity (96%) and negative predictive value (87%), while specificity was 23% and positive predictive value was 56%. Overall, specific, relapse-free, and distant metastasis-free survivals were similar among STARD3 positive and negative groups, independently of other prognosis factors. Conclusion: NST is an opportunity for HER2-positive cancers. In this series of over a hundred HER2-positive and non-metastatic patients, a STARD3-negative score was associated with the absence of pathological complete response. This study suggests that determining STARD3 overexpression status on initial biopsies of HER2-positive tumors is an added value for the management of a subset of patients with high probability of no pathological response. Full article
(This article belongs to the Special Issue Biomarkers in HER2 Positive Breast Cancer)
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