{"doi":"10.1093/jncics/pkaf022","title":"Revisiting surrogacy of pathological complete response for long-term survival in triple-negative breast cancer","abstract":"BACKGROUND: Pathological complete response has been used as a primary endpoint in neoadjuvant trials in early stage triple-negative breast cancer, and the Food and Drug Administration accepted pathological complete response as a surrogate endpoint for long-term survival outcomes in high-risk early stage breast cancer for new drug approval. However, there is insufficient trial-level data to robustly support pathological complete response as a surrogate for long-term survival in triple-negative breast cancer. METHODS: A systematic literature review was performed to identify randomized clinical trials of neoadjuvant systemic therapy for patients with clinical stage I-III triple-negative breast cancer. Data of odds ratios (ORs) for pathological complete response and hazard ratios (HRs) for event-free survival and overall survival were extracted. Disease-free survival was used as an alternative when event-free survival data were unavailable. A linear regression model on a logarithmic scale, coefficient of difference, and 95% confidential interval (CI) were calculated to assess the trial-level association between odds ratio for pathological complete response and hazard ratio for overall survival and event-free survival. RESULTS: Eight trials with 2342 patients were included. Three trials tested immune checkpoint inhibitors. Coefficient of difference (R2) was 0.2 for hazard ratio of event-free survival (95% CI = 0.17 to 0.22, P = .27), and R2 for hazard ratio of overall survival was 0.19 (95% CI = 0.17 to 0.22, P = .33). CONCLUSIONS: There is no strong evidence to support using pathological complete response as a surrogate marker for event-free survival or overall survival in early stage triple-negative breast cancer at the trial level. Because of the necessity of minimizing drug approval delay with reliable long-term outcome, further studies of surrogate markers in early stage triple-negative breast cancer are warranted.","journal":"JNCI Cancer Spectrum","year":2025,"id":531139,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"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":858656,"name":"Zao Zhang","orcid":"0000-0003-3552-8078","position":1,"is_corresponding":false},{"id":872717,"name":"Ryota Sato","orcid":"0000-0001-8806-2852","position":2,"is_corresponding":false},{"id":242501,"name":"Stanley Lipkowitz","orcid":"0000-0002-6103-2255","position":3,"is_corresponding":false},{"id":1178513,"name":"Takeo Fujii","orcid":"0000-0003-3747-2688","position":4,"is_corresponding":false},{"id":1411026,"name":"Toru Yoshino","orcid":"0000-0003-1586-2706","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39992221","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":[]}