| Title: |
Tumor Intrinsic Subtypes and Gene Expression Signatures in Early-Stage ERBB2/HER2-Positive Breast Cancer: A Pooled Analysis of CALGB 40601, NeoALTTO, and NSABP B-41 Trials. |
| Authors: |
Fernandez-Martinez, A; Rediti, M; Tang, G; Pascual, T; Hoadley, KA; Venet, D; Rashid, NU; Spears, PA; Islam, MN; El-Abed, S; Bliss, J; Lambertini, M; Di Cosimo, S; Huobe, J; Goerlitz, D; Hu, R; Lucas, PC; Swain, SM; Sotiriou, C; Perou, CM; Carey, LA |
| Contributors: |
Bliss, Judith |
| Publisher Information: |
AMER MEDICAL ASSOC |
| Publication Year: |
2024 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Adult; Aged; Female; Humans; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Tumor; Breast Neoplasms; Gene Expression Profiling; Lapatinib; Neoadjuvant Therapy; Neoplasm Staging; Receptor; ErbB-2; Retrospective Studies; Transcriptome; Trastuzumab |
| Subject Geographic: |
United States |
| Description: |
IMPORTANCE: Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2-positive early breast cancer (EBC). OBJECTIVE: To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.5 years. Gene expression profiling by RNA sequencing was obtained from 758 samples, and intrinsic subtypes and 618 gene expression signatures were calculated. Data analyses were performed from June 1, 2020, to January 1, 2023. MAIN OUTCOMES AND MEASURES: The association of clinical variables and gene expression biomarkers with pCR and EFS were studied by logistic regression and Cox analyses. RESULTS: In the pooled analysis, of 758 women, median age was 49 years, 12% were Asian, 6% Black, and 75% were White. Overall, pCR results were associated with EFS in the ERBB2-enriched (hazard ratio [HR], 0.45; 95% CI, 0.29-0.70; P < .001) and basal-like (HR, 0.19; 95% CI, 0.04-0.86; P = .03) subtypes but not in luminal A or B tumors. Dual trastuzumab plus lapatinib blockade over trastuzumab alone had a trend toward EFS benefit in the intention-to-treat population; however, in the ERBB2-enriched subtype there was a significant and independent EFS benefit of trastuzumab plus lapatinib vs trastuzumab alone (HR, 0.47; 95% CI, 0.27-0.83; P = .009). Overall, 275 of 618 gene expression signatures (44.5%) were significantly associated with pCR and 9 of 618 (1.5%) with EFS. The ERBB2/HER2 amplicon and multiple immune signatures were significantly associated with pCR. Luminal-related signatures were associated with lower pCR rates but better EFS, especially among patients with residual disease and ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print; 611; application/pdf |
| Language: |
English |
| ISSN: |
2374-2445; 2374-2437 |
| Relation: |
2816978; JAMA Oncology, 2024, 10 (5), pp. 603 - 611; https://repository.icr.ac.uk/handle/internal/6327 |
| DOI: |
10.1001/jamaoncol.2023.7304 |
| Availability: |
https://doi.org/10.1001/jamaoncol.2023.7304; https://repository.icr.ac.uk/handle/internal/6327 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.C3673126 |
| Database: |
BASE |