Systemic Therapies for HER2-Positive Advanced Breast Cancer
Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, sig...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/1/23 |
| _version_ | 1797359051321901056 |
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| author | Vasileios Angelis Alicia F. C. Okines |
| author_facet | Vasileios Angelis Alicia F. C. Okines |
| author_sort | Vasileios Angelis |
| collection | DOAJ |
| description | Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, significant advances in our understanding of the underlying molecular mechanisms of HER2-driven oncogenesis have translated into pharmaceutical advances, with the developing of increasingly sophisticated therapies directed against HER2. These include novel, more potent selective HER2 tyrosine kinase inhibitors (TKIs); new anti-HER2 antibody-drug conjugates; and dual epitope targeting antibodies, with more advanced pharmacological properties and higher affinity. With the introduction of adjuvant T-DM1 for incomplete responders to neoadjuvant therapy, fewer patients are relapsing, but for those who do relapse, disease that may be resistant to standard first- and second-line therapies requires new approaches. Furthermore, the risk of CNS relapse has not been abrogated by current (neo)adjuvant strategies; therefore, current research efforts are being directed towards this challenging site of metastatic disease. In this article, we review the currently available clinical data informing the effective management of HER2-positive breast cancer beyond standard first-line therapy with pertuzumab, trastuzumab, and taxanes, and the management of relapse in patients who have already been exposed to both these agents and T-DM1 for early breast cancer (EBC). We additionally discuss novel anti-HER2 targeted agents and combinations in clinical trials, which may be integrated into standard treatment paradigms in the future. |
| first_indexed | 2024-03-08T15:10:06Z |
| format | Article |
| id | doaj.art-1a8bac0e005545358aaf7a8e77732002 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T15:10:06Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1a8bac0e005545358aaf7a8e777320022024-01-10T14:52:20ZengMDPI AGCancers2072-66942023-12-011612310.3390/cancers16010023Systemic Therapies for HER2-Positive Advanced Breast CancerVasileios Angelis0Alicia F. C. Okines1Department of Medicine, Royal Marsden NHS Foundation Trust, Fulham Road, Chelsea, London SW3 6JJ, UKDepartment of Medicine, Royal Marsden NHS Foundation Trust, Fulham Road, Chelsea, London SW3 6JJ, UKDespite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, significant advances in our understanding of the underlying molecular mechanisms of HER2-driven oncogenesis have translated into pharmaceutical advances, with the developing of increasingly sophisticated therapies directed against HER2. These include novel, more potent selective HER2 tyrosine kinase inhibitors (TKIs); new anti-HER2 antibody-drug conjugates; and dual epitope targeting antibodies, with more advanced pharmacological properties and higher affinity. With the introduction of adjuvant T-DM1 for incomplete responders to neoadjuvant therapy, fewer patients are relapsing, but for those who do relapse, disease that may be resistant to standard first- and second-line therapies requires new approaches. Furthermore, the risk of CNS relapse has not been abrogated by current (neo)adjuvant strategies; therefore, current research efforts are being directed towards this challenging site of metastatic disease. In this article, we review the currently available clinical data informing the effective management of HER2-positive breast cancer beyond standard first-line therapy with pertuzumab, trastuzumab, and taxanes, and the management of relapse in patients who have already been exposed to both these agents and T-DM1 for early breast cancer (EBC). We additionally discuss novel anti-HER2 targeted agents and combinations in clinical trials, which may be integrated into standard treatment paradigms in the future.https://www.mdpi.com/2072-6694/16/1/23advanced breast cancerantibody-drug conjugatescentral nervous systemHER2-positiveresistancetyrosine kinase inhibitors |
| spellingShingle | Vasileios Angelis Alicia F. C. Okines Systemic Therapies for HER2-Positive Advanced Breast Cancer Cancers advanced breast cancer antibody-drug conjugates central nervous system HER2-positive resistance tyrosine kinase inhibitors |
| title | Systemic Therapies for HER2-Positive Advanced Breast Cancer |
| title_full | Systemic Therapies for HER2-Positive Advanced Breast Cancer |
| title_fullStr | Systemic Therapies for HER2-Positive Advanced Breast Cancer |
| title_full_unstemmed | Systemic Therapies for HER2-Positive Advanced Breast Cancer |
| title_short | Systemic Therapies for HER2-Positive Advanced Breast Cancer |
| title_sort | systemic therapies for her2 positive advanced breast cancer |
| topic | advanced breast cancer antibody-drug conjugates central nervous system HER2-positive resistance tyrosine kinase inhibitors |
| url | https://www.mdpi.com/2072-6694/16/1/23 |
| work_keys_str_mv | AT vasileiosangelis systemictherapiesforher2positiveadvancedbreastcancer AT aliciafcokines systemictherapiesforher2positiveadvancedbreastcancer |