Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. [Review]
Citation: Lancet. 384(9938):164-72, 2014 Jul 12.PMID: 24529560Form of publication: Journal ArticleMedline article type(s): Journal Article | Meta-Analysis | Research Support, U.S. Gov't, P.H.S. | ReviewSubject headings: *Breast Neoplasms/pa [Pathology] | *Carcinoma, Ductal, Breast/pa [Pathology] | Adult | Antibodies, Monoclonal, Humanized/ad [Administration & Dosage] | Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] | Breast Neoplasms/th [Therapy] | Carcinoma, Ductal, Breast/th [Therapy] | Chemotherapy, Adjuvant | Disease-Free Survival | Female | Humans | Middle Aged | Neoplasms, Hormone-Dependent/pa [Pathology] | Neoplasms, Hormone-Dependent/th [Therapy] | Preoperative Care/mt [Methods] | Randomized Controlled Trials as Topic | Treatment OutcomeYear: 2014Local holdings: Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1983 - 2007ISSN:- 0140-6736
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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Journal Article | MedStar Authors Catalog | Article | 24529560 | Available | 24529560 |
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1983 - 2007
BACKGROUND: Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS.
FINDINGS: We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 044, 95% CI 039-051; ypT0/is ypN0: 048, 043-054) and OS (036, 030-044; 036, 031-042) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 060, 95% CI 055-066; OS 051, 045-058). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 024, 95% CI 018-033; OS: 016, 011-025) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 015, 009-027; OS: 008, 003, 022). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=003, 95% CI 000-025) and OS (R(2)=024, 000-070).
FUNDING: US Food and Drug Administration. Copyright 2014 Elsevier Ltd. All rights reserved.
INTERPRETATION: Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS.
METHODS: We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response--ypT0 ypN0, ypT0/is ypN0, and ypT0/is--for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS.
English