Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan
Breast cancer (BC) is the leading cause of cancer-related mortality among women. The backbone of first-line treatment in HR+/HER2+ BC is dual anti-HER2 blockade combined with taxane chemotherapy. Although this regimen exhibits high rates of response and disease control in both HR+ and HR− cohorts, s...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1484750/full |
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| author | Ünal Metin Tokat Ashkan Adibi Ashkan Adibi Esranur Aydın Şevval Nur Bilgiç Eylül Özgü Onur Tutar Mutlu Demiray |
| author_facet | Ünal Metin Tokat Ashkan Adibi Ashkan Adibi Esranur Aydın Şevval Nur Bilgiç Eylül Özgü Onur Tutar Mutlu Demiray |
| author_sort | Ünal Metin Tokat |
| collection | DOAJ |
| description | Breast cancer (BC) is the leading cause of cancer-related mortality among women. The backbone of first-line treatment in HR+/HER2+ BC is dual anti-HER2 blockade combined with taxane chemotherapy. Although this regimen exhibits high rates of response and disease control in both HR+ and HR− cohorts, some patients could have intrinsic or develop acquired resistance to trastuzumab and/or pertuzumab. Here, we achieved a near-complete response in HR+ HER2-amplified and overexpressing metastatic BC twice through molecular tumor board (MTB) discussions: initially, with trastuzumab deruxtecan (T-DXd) when HER2 IHC was positive, and, then, with neratinib plus fulvestrant plus paclitaxel when IHC was negative. Our case presents GATA3 and NOTCH2 mutations, MCL1 and CKS1B amplifications, as well as ERBB3/KRAS overexpression and ER signaling as potential new mechanisms of resistance to T-DXd. Furthermore, we demonstrated that triplet combination could induce a remarkable response in the T-DXd–refractory setting, which could be explored in future clinical trials in HR+ and HER2-activated (by RNA or protein overexpression, amplification, and mutation) patients. Our case also highlights the importance of the MTBs to dynamically and reactively manage the course of disease and treatment on a per-patient basis. |
| format | Article |
| id | doaj-art-6af26a460ffe43a382c2101e7ed95639 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-6af26a460ffe43a382c2101e7ed956392025-01-27T09:29:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.14847501484750Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecanÜnal Metin Tokat0Ashkan Adibi1Ashkan Adibi2Esranur Aydın3Şevval Nur Bilgiç4Eylül Özgü5Onur Tutar6Mutlu Demiray7Precision Oncology Center, Medicana Health Group, Istanbul, TürkiyePrecision Oncology Center, Medicana Health Group, Istanbul, TürkiyeDivision of Cancer Genetics, Department of Basic Oncology, Institute of Oncology, Istanbul University, Istanbul, TürkiyePrecision Oncology Center, Medicana Health Group, Istanbul, TürkiyePrecision Oncology Center, Medicana Health Group, Istanbul, TürkiyePrecision Oncology Center, Medicana Health Group, Istanbul, TürkiyeDepartment of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, TürkiyePrecision Oncology Center, Medicana Health Group, Istanbul, TürkiyeBreast cancer (BC) is the leading cause of cancer-related mortality among women. The backbone of first-line treatment in HR+/HER2+ BC is dual anti-HER2 blockade combined with taxane chemotherapy. Although this regimen exhibits high rates of response and disease control in both HR+ and HR− cohorts, some patients could have intrinsic or develop acquired resistance to trastuzumab and/or pertuzumab. Here, we achieved a near-complete response in HR+ HER2-amplified and overexpressing metastatic BC twice through molecular tumor board (MTB) discussions: initially, with trastuzumab deruxtecan (T-DXd) when HER2 IHC was positive, and, then, with neratinib plus fulvestrant plus paclitaxel when IHC was negative. Our case presents GATA3 and NOTCH2 mutations, MCL1 and CKS1B amplifications, as well as ERBB3/KRAS overexpression and ER signaling as potential new mechanisms of resistance to T-DXd. Furthermore, we demonstrated that triplet combination could induce a remarkable response in the T-DXd–refractory setting, which could be explored in future clinical trials in HR+ and HER2-activated (by RNA or protein overexpression, amplification, and mutation) patients. Our case also highlights the importance of the MTBs to dynamically and reactively manage the course of disease and treatment on a per-patient basis.https://www.frontiersin.org/articles/10.3389/fonc.2024.1484750/fullbreast cancerprecision oncologycancer genomicsHER2 antibody-drug conjugates (HER2 ADC)trastuzumab deruxtecanneratinib |
| spellingShingle | Ünal Metin Tokat Ashkan Adibi Ashkan Adibi Esranur Aydın Şevval Nur Bilgiç Eylül Özgü Onur Tutar Mutlu Demiray Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan Frontiers in Oncology breast cancer precision oncology cancer genomics HER2 antibody-drug conjugates (HER2 ADC) trastuzumab deruxtecan neratinib |
| title | Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan |
| title_full | Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan |
| title_fullStr | Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan |
| title_full_unstemmed | Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan |
| title_short | Case report: Near-complete response to neratinib-based treatment in HR-positive HER2-amplified metastatic breast cancer refractory to trastuzumab deruxtecan |
| title_sort | case report near complete response to neratinib based treatment in hr positive her2 amplified metastatic breast cancer refractory to trastuzumab deruxtecan |
| topic | breast cancer precision oncology cancer genomics HER2 antibody-drug conjugates (HER2 ADC) trastuzumab deruxtecan neratinib |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1484750/full |
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