Adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer Journal Article
| Authors: | Metzger Filho, O.; Ballman, K.; Campbell, J.; Liu, M.; Ligibel, J.; Watson, M.; Chen, E.; Du, L.; Stover, D.; Carey, L.; Partridge, A.; Kirshner, J.; Muss, H.; Hudis, C.; Winer, E. P.; Norton, L.; Fraser Symmans, W. |
| Article Title: | Adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer |
| Abstract: | PURPOSEIn light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.METHODSIn all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-Term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers.RESULTSDose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P =.0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not.CONCLUSIONAt 12-year follow-up, C9741 confirmed the sustained long-Term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status. © 2025 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; human tissue; aged; disease-free survival; middle aged; primary tumor; major clinical study; overall survival; mortality; dose response; disease free survival; chemotherapy, adjuvant; outcome assessment; follow up; antineoplastic agent; cell proliferation; metabolism; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; cohort analysis; pathology; dose-response relationship, drug; breast neoplasms; tumor marker; rna; tumor burden; multicenter study; adjuvant chemotherapy; breast tumor; clinical evaluation; receptors, estrogen; phase 3 clinical trial; estrogen receptor; progesterone receptor; drug therapy; predictive value; cancer prognosis; long term survival; endocrine function; dose densification; humans; prognosis; human; female; article; hormone receptor positive breast cancer; biomarkers, tumor |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 10 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-04-01 |
| Start Page: | 1229 |
| End Page: | 1239 |
| Language: | English |
| DOI: | 10.1200/jco-24-01875 |
| PUBMED: | 39746162 |
| PROVIDER: | scopus |
| PMCID: | PMC11954676 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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