Association of baseline ROR1 and ROR2 gene expression with clinical outcomes in the I-SPY2 neoadjuvant breast cancer trial.

Autor: Parker BA; Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA. baparker@health.ucsd.edu., Shatsky RA; Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA., Schwab RB; Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA., Wallace AM; Department of Surgery and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA., Wolf DM; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA., Hirst GL; Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Brown-Swigart L; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA., Esserman LJ; Department of Surgery, University of California San Francisco, San Francisco, CA, USA., van 't Veer LJ; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA., Ghia EM; Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.; Center for Novel Therapeutics, University of California San Diego, La Jolla, CA, USA., Yau C; Department of Surgery, University of California San Francisco, San Francisco, CA, USA., Kipps TJ; Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.; Center for Novel Therapeutics, University of California San Diego, La Jolla, CA, USA.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2023 Jun; Vol. 199 (2), pp. 281-291. Date of Electronic Publication: 2023 Apr 08.
DOI: 10.1007/s10549-023-06914-2
Abstrakt: Purpose: ROR1 and ROR2 are Type 1 tyrosine kinase-like orphan receptors for Wnt5a that are associated with breast cancer progression. Experimental agents targeting ROR1 and ROR2 are in clinical trials. This study evaluated whether expression levels of ROR1 or ROR2 correlated with one another or with clinical outcomes.
Methods: We interrogated the clinical significance of high-level gene expression of ROR1 and/or ROR2 in the annotated transcriptome dataset from 989 patients with high-risk early breast cancer enrolled in one of nine completed/graduated/experimental and control arms in the neoadjuvant I-SPY2 clinical trial (NCT01042379).
Results: High ROR1 or high ROR2 was associated with breast cancer subtypes. High ROR1 was more prevalent among hormone receptor-negative and human epidermal growth factor receptor 2-negative (HR-HER2-) tumors and high ROR2 was less prevalent in this subtype. Although not associated with pathologic complete response, high ROR1 or high ROR2 each was associated with event-free survival (EFS) in distinct subtypes. High ROR1 associated with a worse EFS in HR + HER2- patients with high post-treatment residual cancer burden (RCB-II/III) (HR 1.41, 95% CI = 1.11-1.80) but not in patients with minimal post-treatment disease (RCB-0/I) (HR 1.85, 95% CI = 0.74-4.61). High ROR2 associated with an increased risk of relapse in patients with HER2 + disease and RCB-0/I (HR 3.46, 95% CI = 1.33-9.020) but not RCB-II/III (HR 1.07, 95% CI = 0.69-1.64).
Conclusion: High ROR1 or high ROR2 distinctly identified subsets of breast cancer patients with adverse outcomes. Further studies are warranted to determine if high ROR1 or high ROR2 may identify high-risk populations for studies of targeted therapies.
(© 2023. The Author(s).)
Databáze: MEDLINE
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