Gene linked to survival after anthracyclines, anti-HER2 therapies for breast cancer
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Genetic variants of the UACA gene, a critical regulator of tumor suppressor Par-4, appeared associated with OS among patients who received anthracyclines and HER2-targeted therapy, according to a study published in NPJ Breast Cancer.
Rationale and methods
“Hundreds of genetic variations have been linked to breast cancer risk, but to date, very few have been robustly linked to survival outcomes after a breast cancer diagnosis,” Qianqian Zhu, PhD, associate professor of oncology in the department of biostatistics and bioinformatics and co-director of the biostatistics and statistical genomics resource at Roswell Park Comprehensive Cancer Center, told Healio.
Researchers conducted a trans-ethnic meta genome-wide association study of OS among 3,973 patients with breast cancer included in the Pathways Study.
Key findings
Results showed an association of a locus spanning the UACA gene with OS among patients receiving Par-4-dependent chemotherapies at a level of genome-wide significance (P = 1.27 × 109). Researchers confirmed the findings in a meta-analysis across four independent prospective breast cancer cohorts (combined HR = 1.84; P = 1.28 × 1011).
Moreover, results of a transcriptome-wide association study showed a significant association of higher UACA gene expression with worse OS (P = 4.68 × 107).
“These observations are biologically plausible, and we replicated the observations in a study of women with breast cancer in Shanghai,” Zhu said.
Implications
If the findings are further replicated in other breast cancer studies, a genetic test to identify variants in the UACA gene can support the goal of precision oncology to tailor treatments for those who would benefit most, Zhu said.
“Such a test would enable clinicians to personalize treatment plans by determining which patients will best respond to anthracycline or HER2-targeted therapy before treatment begins,” Zhu added. “These findings also highlight the potential of targeting both the UACA gene and the Par-4 pathway as new approaches to improving outcomes of patients with breast cancer.”
Zhu and colleagues plan to replicate the findings in additional cohorts of patients with breast cancer that have genetic information and treatment details.
“We are also looking into the biology behind our findings to learn more about the Par-4 pathway and how it interacts with these treatments,” she said.
References:
Researchers identify gene that predicts breast cancer patients’ treatment outcomes (press release). https://www.roswellpark.org/newsroom/202203-researchers-identify-gene-predicts-breast-cancer-patients-treatment-outcomes. Published March 23, 2022. Accessed May 18, 2022.
Zhu Q, et al. NPJ Breast Cancer. 2022;doi:10.1038/s41523-022-00401-5.
For more information:
Qianqian Zhu, PhD, can be reached at Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY 14203; email:qianqian.zhu@roswellpark.org.
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