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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Tuesday, June 21, 2022
For patients with breast cancer receiving treatment with anthracyclines and/or anti-HER2 therapy, the UACA locus may serve as a genetic predictor of patient outcomes, according to a transethnic meta–genome-wide association study published in npj Breast Cancer. The UACA locus may pave the way for establishing novel treatment strategies for this patient population, explained Lawrence H. Kushi, ScD, of the Kaiser Permanente Northern California, Oakland, and colleagues.
“It is amazing that we started an agnostic search across the genome for genetic markers associated with breast cancer outcomes and identified UACA as a promising gene predictive of treatment outcomes for two commonly used agents for breast cancer,” commented coauthor Song Yao, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, in an institutional press release.
From 2006 to 2013, a total of 3,973 patients with breast cancer were recruited from the Pathways Study. Saliva and blood specimens were collected within 2 months of pathology-confirmed diagnosis. Genetic analysis was then performed on these specimens.
The study authors identified an association between the UACA locus and overall survival in patients taking Par-4 dependent chemotherapies. UACA is a known regulator of the tumor suppressor Par-4.
In addition, a meta-analysis was performed across four independent prospective breast cancer cohorts; all confirmed the association between the UACA locus and overall survival (combined hazard ratio = 1.84). The extent of this association was evaluated with a transcriptome-wide association study, which demonstrated that increased levels of UACA were associated with worse overall survival for patients.
“We anticipate that the knowledge of the UACA genotypes or expression level would help physicians identify patients who are most likely to benefit from anthracyclines and HER2-targeted therapy and provide complementary or alternative treatment to those who are not,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
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