Publications

Detailed Information

Genomic Profiling of Premenopausal HR+ and HER2-Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib

Cited 19 time in Web of Science Cited 15 time in Scopus
Authors

Bardia, Aditya; Su, Fei; Solovieff, Nadia; Im, Seock-Ah; Sohn, Joohyuk; Lee, Keun Seok; Campos-Gomez, Saul; Jung, Kyung Hae; Colleoni, Marco; Villanueva Vazquez, Rafael; Franke, Fabio; Hurvitz, Sara; Harbeck, Nadia; Chow, Louis; Taran, Tetiana; Lorenc, Karen Rodriguez; Babbar, Naveen; Tripathy, Debu; Lu, Yen-Shen

Issue Date
2021-08
Publisher
American Society of Clinical Oncology
Citation
JCO Precision Oncology, Vol.5, pp.1408-1420
Abstract
PURPOSE This analysis evaluated the genomic landscape of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and the association of genetic alterations with response to ribociclib in the phase III MONALEESA-7 trial. METHODS Premenopausal patients were randomly assigned 1:1 to receive endocrine therapy plus ribociclib or placebo. Plasma collected at baseline was sequenced using targeted next-generation sequencing for approximately 600 relevant cancer genes. The association of circulating tumor DNA alterations with progression-free survival (PFS) was evaluated to identify biomarkers of response and resistance to ribociclib. RESULTS Baseline circulating tumor DNA was sequenced in 565 patients; 489 had evidence of >= 1 alteration. The most frequent alterations included PIK3CA (28%), TP53 (19%), CCND1 (10%), MYC (8%), GATA3 (8%), receptor tyrosine kinases (17%), and the Chr8p11.23 locus (12%). A treatment benefit of ribociclib was seen with wild-type (hazard ratio [HR] 0.45 [95% CI, 0.33 to 0.62]) and altered (HR 0.57 [95% CI, 0.36 to 0.9]) PIK3CA. Overall, patients with altered CCND1 had shorter PFS regardless of treatment, suggesting CCND1 as a potential prognostic biomarker. Benefit with ribociclib was seen in patients with altered (HR 0.21 [95% CI, 0.08 to 0.54]) or wild-type (HR 0.52 [95% CI, 0.39 to 0.68]) CCND1, but greater benefit was observed with altered, suggesting predictive potential of CCND1. Alterations in TP53, MYC, Chr8p11.23 locus, and receptor tyrosine kinases were associated with worse PFS, but ribociclib benefit was independent of alteration status. CONCLUSION In this study-to our knowledge, the first large study of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer-multiple genomic alterations were associated with poor outcome. A PFS benefit of ribociclib was observed regardless of gene alteration status, although in this exploratory analysis, a magnitude of benefits varied by alteration.
ISSN
2473-4284
URI
https://hdl.handle.net/10371/177118
DOI
https://doi.org/10.1200/PO.20.00445
Files in This Item:
There are no files associated with this item.
Appears in Collections:

Related Researcher

  • College of Medicine
  • Department of Medicine
Research Area Clinical Medicine

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share