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Comprehensive Genomic Profiling for Metastatic Breast Cancer: Current Status and...
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Comprehensive Genomic Profiling for Metastatic Breast Cancer: Current Status and Future Perspectives

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

Deadline for manuscript submissions: 30 September 2024 | Viewed by 2457

Special Issue Editors

Dr. Hiroshi Tada

E-Mail Website
Guest Editor
Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan
Interests: breast cancer; genomics; transcriptomics
Dr. Hiroko Masuda

E-Mail Website
Guest Editor
Department of Breast Surgical Oncology, School of Medicine, Showa University, Tokyo 142-8666, Japan
Interests: breast cancer; TNBC; mRNA analysis; drug development; clinical trials

Special Issue Information

Dear Colleagues,

Over the past 20 years, advances in genomic analysis of breast cancer have allowed for the constant evolution of clinically relevant subtypes, from immunohistochemically defined groups to molecular profiles. Advanced comprehensive genomic profiling and multiple targeted therapeutics promoted research on molecular tumor characteristics and led to the development of a new approach for metastatic breast cancer (mBC). Broad implementation of comprehensive genomic profiling across an institution is feasible. During this period, the number of genotype selection trials for breast cancer has steadily increased.

While several independent studies suggest better outcomes for the use of molecularly targeted agents compared to conventional therapies, others did not improve outcomes. These conflicting results highlight one of the major problems in precision oncology: the accurate practical interpretation of biomarkers for patient selection.

There are still new opportunities for the improvement of precision medicine for mBC, as evidence supporting this approach is still missing. This is because effectively implementing such precision medicine is not easy and requires solutions that consider technical issues, inter- and intra-tumor diversity, and spatial and temporal evolution.

In addition, a better understanding of the role of genomic alterations and proteins in key signaling pathways in breast cancer progression is needed for more effective treatment.

This Special Issue focuses on the role of comprehensive genomic profiling in mBC, including both translational and clinical aspects of understanding them to find a potential strategy for breast cancer.

In this Special Issue, original research articles and reviews are welcome.

We look forward to your contributions.

Dr. Hiroshi Tada
Dr. Hiroko Masuda
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. 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

  • breast cancer
  • comprehensive genomic profiling
  • molecular matched therapy
  • mBC
  • signaling pathways

Published Papers (2 papers)

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Research

16 pages, 2403 KiB  
Article
Homologous Recombination Repair Gene Alterations Are Associated with Tumor Mutational Burden and Survival of Immunotherapy
by Mamoru Ito, Makoto Kubo, Hitomi Kawaji, Yoshiki Otsubo, Kanako Kurata, Hikaru Abutani, Mikita Suyama, Yoshinao Oda, Tomoharu Yoshizumi, Masafumi Nakamura and Eishi Baba
Cancers 2023, 15(23), 5608; https://doi.org/10.3390/cancers15235608 - 27 Nov 2023
Viewed by 846
Abstract
Background: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons. Methods: In an observational clinical study [...] Read more.
Background: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons. Methods: In an observational clinical study of FoundationOne® CDx, potential biomarkers were explored and the cause of testing failure was investigated. A total of 220 cancer patients were enrolled in the study during the period from 2018 to 2019 at Kyushu University Hospital. Results: The primary tumor sites of the 220 cases were breast (115), colon (29), stomach (19), and pancreas (20). The present dataset suggested that homologous recombination repair (HRR) gene alterations were positively associated with tumor mutational burden-high (TMB-high) (p = 0.0099). A public dataset confirmed that patients with HRR gene alterations had a higher TMB and showed significantly longer survival of immunotherapy. In the present study, 18 cases failed sequencing. A lower percentage of tumor cell nuclei was the most common reason for testing failures (p = 0.037). Cases that received neoadjuvant chemotherapy before sampling tended to fail testing. Conclusions: HRR gene alterations can be a potential biomarker predicting TMB-high and a good response to immunotherapy. For successful sequencing, samples with lower percentages of tumor cell nuclei and previous neoadjuvant chemotherapy should be avoided. Full article
(This article belongs to the Special Issue Comprehensive Genomic Profiling for Metastatic Breast Cancer: Current Status and Future Perspectives)
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12 pages, 2295 KiB  
Article
Concordance of Targeted Sequencing from Circulating Tumor DNA and Paired Tumor Tissue for Early Breast Cancer
by Chi-Cheng Huang, Yi-Fang Tsai, Chun-Yu Liu, Pei-Ju Lien, Yen-Shu Lin, Ta-Chung Chao, Chin-Jung Feng, Yen-Jen Chen, Jiun-I Lai, Han-Fang Cheng, Bo-Fang Chen, Chih-Yi Hsu, Jen-Hwey Chiu and Ling-Ming Tseng
Cancers 2023, 15(18), 4475; https://doi.org/10.3390/cancers15184475 - 08 Sep 2023
Viewed by 1201
Abstract
In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The [...] Read more.
In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The liquid biopsy detection rate was 39% (all-stage breast cancers, n = 612). Among 246 early-stage patients assayed for both ctDNA and matched tumor, the cfDNA assay detected 73 (29.6%) and the comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (χ2 test, p = 0.001). In total, 67 (25.6%) cases tested positive on both platforms, while the cfDNA and comprehensive assays detected an additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while the PIK3CA (39.4%), AKT1 (45.9%), and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers, considering that the concordance rate between tumor and liquid biopsy was only one-quarter. Full article
(This article belongs to the Special Issue Comprehensive Genomic Profiling for Metastatic Breast Cancer: Current Status and Future Perspectives)
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