{"doi":"10.1016/j.clbc.2025.06.004","title":"Sequential Therapy With HER2 Tyrosine Kinase Inhibitors in Patients With HER2-Positive Metastatic Breast Cancer","abstract":"Purpose HER2-targeted tyrosine kinase inhibitors (TKIs) tucatinib, lapatinib and neratinib are standard agents for treatments of HER2-positive (HER2+) metastatic breast cancer. Due to their penetration through the blood-brain barrier, these agents are especially beneficial for patients with brain metastases. To date, limited data exists on the sequential use of different HER2-targeted TKIs, and it is unknown if reusing the same TKI as a part of different treatment regimens provides clinical benefits. Methods We performed a retrospective single institution study (IRB 23-2337) and identified N=105 patients with HER2+ metastatic breast cancer and a TKI regimen of at least 1 month. We then performed a manual abstraction to identify patients who had at least 2 TKI regimens (N=24) and estimated time on treatment (median and range in months). Best responses to TKI treatments were evaluated by MD review. Patients were censored at the time of the last follow up when the end of treatment data were not available. Results In our patient cohort, 14 of 24 patients (58%) stayed on the second or third TKI regimen for greater than 6 months, and 10 of 24 patients (42%) were on the subsequent TKI regimen(s) for longer than the first one. Time on a non-TKI regimen between the first and second TKI was not associated with the duration of benefit from the second TKI. Conclusion Our data support using different HER2-targeted TKI regimens in sequence, offering additional effective treatment options for patients with HER2+ metastatic breast cancer, including patients with brain metastases. Micro-abstract HER2-targeted tyrosine kinase inhibitors (TKIs) are standard treatment for HER2+ metastatic breast cancer. To date, limited data exist on the sequential use of HER2-targeted TKIs, and it is unknown if reusing the same TKI as a part of different treatment regimens provides clinical benefits. Here we present comprehensive single institution real-world data showing persistence of clinical benefit for repeated and sequential use of HER2-targeted TKIs. These results support using different HER2-targeted TKI regimens in sequence, offering additional effective treatment options for patients with HER2+ metastatic breast cancer, including patients with brain metastases.","journal":"Clinical Breast Cancer","year":2025,"id":539586,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1086673,"name":"Hannah Parris","orcid":"0009-0008-6815-7908","position":1,"is_corresponding":false},{"id":141103,"name":"Long Liu","orcid":"0000-0002-9679-9130","position":2,"is_corresponding":false},{"id":1426631,"name":"Stephanie Giangiuli","orcid":"0000-0001-6966-8023","position":3,"is_corresponding":false},{"id":455482,"name":"Dexiang Gao","orcid":"0000-0003-3920-7060","position":4,"is_corresponding":false},{"id":260393,"name":"Jennifer R. Diamond","orcid":"0000-0002-0703-2772","position":5,"is_corresponding":false},{"id":1427130,"name":"Radhika Acharya-Leon","orcid":null,"position":6,"is_corresponding":false},{"id":234998,"name":"Peter Kabos","orcid":"0000-0003-1500-471X","position":7,"is_corresponding":false},{"id":441767,"name":"Virginia F. Borges","orcid":"0000-0003-1158-7524","position":8,"is_corresponding":false},{"id":754472,"name":"Elena Shagisultanova","orcid":"0000-0003-1389-1116","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:52:30.048313Z","pmid":"40610321","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}