A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11.

Autor:	Stearns V; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine, Baltimore, Maryland., Jegede OA; Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, Massachusetts., Chang VT; Veterans Administration New Jersey Health Care System, East Orange, New Jersey.; Rutgers New Jersey Medical School, Newark, New Jersey., Skaar TC; Indiana University School of Medicine, Indianapolis, Indiana., Berenberg JL; University of Hawaii Cancer Center, Honolulu, Hawaii., Nand R; Columbia Saint Mary's Hospital, Milwaukee, Wisconsin., Shafqat A; Heartland Cancer Research NCORP-Missouri Baptist Medical Center, Saint Louis, Missouri., Jacobs NL; Minnesota Oncology Hematology, Minneapolis, Minnesota., Luginbuhl W; Abramson Cancer Center at Chester County Hospital, West Chester, Pennsylvania., Gilman P; Main Line Oncology Hematology Associates, Wynnewood, Pennsylvania., Benson AB 3rd; Northwestern Medicine, Chicago, Illinois., Goodman JR; Saint Joseph Mercy Oakland, Pontiac, Michigan., Buchschacher GL Jr; Kaiser Permanente NCORP, Southern California Kaiser Permanente, Los Angeles, California., Henry NL; University of Michigan Rogel Cancer Center, Ann Arbor, Michigan., Loprinzi CL; Mayo Clinic, Rochester, Minnesota., Flynn PJ; Abbott Northwestern Hospital, Woodbury, Minnesota., Mitchell EP; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Fisch MJ; University of Texas MD Anderson Cancer Center, Houston, Texas., Sparano JA; Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, New York., Wagner LI; Wake Forest School of Medicine, Winston Salem, North Carolina.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jul 01; Vol. 30 (13), pp. 2709-2718.
DOI:	10.1158/1078-0432.CCR-23-2137
Abstrakt:	Purpose: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. Patients and Methods: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). Results: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. Conclusions: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu