Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2709-2718 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 30 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jul 1 2024 |
Funding
This study was coordinated by the ECOG-ACRIN Cancer Research Group (Peter J. O\u2019Dwyer, MD, and Mitchell D. Schnall, MD, PhD, group co-chairs) and supported by the NCI of the NIH under award numbers UG1CA189828, UG1CA233196, UG1CA233277, UG1CA233320, UG1CA233178, UG1CA233160, UG1CA232760, UG1CA233341, UG1CA233329, U10CA180821, UG1CA189821, UG1CA189830, U10CA180888, UG1CA189863, and UG1CA189971. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This study was also supported in part by the Susan G. Komen Foundation. We thank the study participants, investigators, and research teams. We acknowledge the contributions of Dr. Judy Manola and the late Dr. David A. Flockhart to the initial design and concept of this trial. We acknowledge the contributions of Alan P. Lyss from the Heartland Cancer Research NCORP to patient recruitment and helpful comments. We thank Judy Murray (Johns Hopkins); Pamela Jane Raper, PhD (Wake Forest); Elizabeth Jeter, PhD; and Elijah Patten (Northwestern) for their assistance. The authors acknowledge Dr. Edith Mitchell\u2019s substantial contributions throughout the study design and analysis and were sad to hear of her unexpected passing during the final revisions of the manuscript.
ASJC Scopus subject areas
- General Medicine
