Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting
Purpose: We aimed to characterize genomic alterations with potential prognostic or predictive significance in patients with metastatic triple-negative breast cancer (mTNBC) treated with chemotherapy in a real-world setting. Patients and methods: Next-generation sequencing with FoundationOne® CDx was...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Breast |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977625000037 |
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| author | Erik Olsson Henrik Lindman Evangelos Digkas Viktoria Thurfjell Haidar Mir Ali Ute Krüger Anna-Karin Wennstig Marie Sundqvist Antonios Valachis |
| author_facet | Erik Olsson Henrik Lindman Evangelos Digkas Viktoria Thurfjell Haidar Mir Ali Ute Krüger Anna-Karin Wennstig Marie Sundqvist Antonios Valachis |
| author_sort | Erik Olsson |
| collection | DOAJ |
| description | Purpose: We aimed to characterize genomic alterations with potential prognostic or predictive significance in patients with metastatic triple-negative breast cancer (mTNBC) treated with chemotherapy in a real-world setting. Patients and methods: Next-generation sequencing with FoundationOne® CDx was conducted primarily on primary tumor tissue from 112 consecutive patients with mTNBC. Genomic alterations were subdivided into canonical oncogenic pathways and noted for their involvement in homologous recombination deficiency (HRD). Altered genes and pathways were correlated with overall survival (OS) and evaluated regarding their association with real-world progression-free survival (rwPFS) in patients treated with different chemotherapy agents. Occurrence of alterations were compared between patients with exceptional response and rapid progression to chemotherapy. Results: After exclusion due to insufficient tumor tissue or clinical data, material from 97 patients was analyzed. The most frequently altered genes were TP53 (82 %), RAD21 (25 %) and PIK3CA (23 %). Altogether, 26 % of patients had an alteration leading to HRD. None of the analyzed alterations were associated with OS. Variants leading to HRD were associated with a prolonged rwPFS in patients treated with platinum-based chemotherapy in the first line setting (hazard ratio [HR], 0.31 [95 % CI: 0.12–0.84]). Exceptional responders more often exhibited alterations in the MYC and RAS/RTK pathways compared to rapid progressors. Conclusions: Patients with tumor alterations in HRD-related genes seem to define subgroups that respond favorably to platinum-based chemotherapy. Further research into the genomic landscape of tumors from patients with rapid progression or exceptional response to different treatment strategies can provide insights into mechanisms of resistance and identify predictive biomarkers. |
| format | Article |
| id | doaj-art-c6c8b2a81f9e4ad18a3b8fc701b73bbe |
| institution | Kabale University |
| issn | 1532-3080 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj-art-c6c8b2a81f9e4ad18a3b8fc701b73bbe2025-02-12T05:30:38ZengElsevierBreast1532-30802025-02-0179103874Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world settingErik Olsson0Henrik Lindman1Evangelos Digkas2Viktoria Thurfjell3Haidar Mir Ali4Ute Krüger5Anna-Karin Wennstig6Marie Sundqvist7Antonios Valachis8Department of Oncology, Uppsala University Hospital, Sweden; Corresponding author. Onkologmottagningen, Akademiska sjukhuset Ingång 101, våning 2, 75185, Uppsala, Sweden.Department of Oncology, Uppsala University Hospital, SwedenDepartment of Oncology, Uppsala University Hospital, SwedenDepartment of Clinical Pathology, Uppsala University Hospital, SwedenDepartment of Surgery, Kalmar Hospital, SwedenDepartment of Clinical Pathology, Kalmar Hospital, SwedenDepartment of Oncology, Sundsvall Hospital, SwedenDepartment of Surgery, Kalmar Hospital, SwedenDepartment of Surgery, Kalmar Hospital, Sweden; Department of Clinical Pathology, Kalmar Hospital, Sweden; Department of Oncology, Örebro University Hospital, SwedenPurpose: We aimed to characterize genomic alterations with potential prognostic or predictive significance in patients with metastatic triple-negative breast cancer (mTNBC) treated with chemotherapy in a real-world setting. Patients and methods: Next-generation sequencing with FoundationOne® CDx was conducted primarily on primary tumor tissue from 112 consecutive patients with mTNBC. Genomic alterations were subdivided into canonical oncogenic pathways and noted for their involvement in homologous recombination deficiency (HRD). Altered genes and pathways were correlated with overall survival (OS) and evaluated regarding their association with real-world progression-free survival (rwPFS) in patients treated with different chemotherapy agents. Occurrence of alterations were compared between patients with exceptional response and rapid progression to chemotherapy. Results: After exclusion due to insufficient tumor tissue or clinical data, material from 97 patients was analyzed. The most frequently altered genes were TP53 (82 %), RAD21 (25 %) and PIK3CA (23 %). Altogether, 26 % of patients had an alteration leading to HRD. None of the analyzed alterations were associated with OS. Variants leading to HRD were associated with a prolonged rwPFS in patients treated with platinum-based chemotherapy in the first line setting (hazard ratio [HR], 0.31 [95 % CI: 0.12–0.84]). Exceptional responders more often exhibited alterations in the MYC and RAS/RTK pathways compared to rapid progressors. Conclusions: Patients with tumor alterations in HRD-related genes seem to define subgroups that respond favorably to platinum-based chemotherapy. Further research into the genomic landscape of tumors from patients with rapid progression or exceptional response to different treatment strategies can provide insights into mechanisms of resistance and identify predictive biomarkers.http://www.sciencedirect.com/science/article/pii/S0960977625000037 |
| spellingShingle | Erik Olsson Henrik Lindman Evangelos Digkas Viktoria Thurfjell Haidar Mir Ali Ute Krüger Anna-Karin Wennstig Marie Sundqvist Antonios Valachis Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting Breast |
| title | Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting |
| title_full | Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting |
| title_fullStr | Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting |
| title_full_unstemmed | Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting |
| title_short | Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting |
| title_sort | genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple negative breast cancer treated in a real world setting |
| url | http://www.sciencedirect.com/science/article/pii/S0960977625000037 |
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