A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)
I. To validate previously identified associations between 10 specific single nucleotide
polymorphisms (single nucleotide polymorphisms [SNPs]) and discontinuation of treatment with
aromatase inhibitors (AIs) due to the development of musculoskeletal symptoms (MSS) among
women with breast cancer.
I. To determine whether other SNPs in cytochrome P450 enzymes (CYP),
glucuronosyltransferases (UGT), Vitamin D, serotonin and other receptors are associated with
discontinuation of treatment due to the development of severe aromatase inhibitor-associated
musculoskeletal symptoms (AIMSS).
II. To determine whether other SNPs in CYP, UGT, Vitamin D, serotonin and other receptors
are associated with the development of other potential complications of AI therapy.
III. To develop a gene signature that can identify patients at risk for developing severe
anastrozole-related AIMSS and other potential complications of AI therapy.
IV. To determine the epidemiology and predictors of severe AIMSS and of AI discontinuation.
V. To describe patient reported outcomes for minority patients with breast cancer treated
VI. To assess the utility of the Patient Reported Outcomes Management Information System
(PROMIS) system to collect patient reported outcomes in a cooperative group study, and
validate the PROMIS Physical Function 20a form in patients with AIMSS.
VII. To develop a model that incorporates patient ratings of treatment burden, fear of
recurrence and adherence behaviors to describe patient decisions to continue or discontinue
VIII. To collect serum samples for future testing for biomarkers of AIMSS.
Patients receive anastrozole orally (PO) once daily (QD) for 12 months.
After the completion of study treatment, patients are followed up for 12 months.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Discontinuation of treatment following development of AIMSS determined by scores on the Health Assessment Questionnaire (HAQ) instrument
Logistic regression will be used to test the association between having a minor allele and the log odds of discontinuation of treatment, adjusting for covariates. A Bonferroni adjustment will be used to account for the simultaneous testing of 10 SNPs; a one-sided p-value of 0.0025 will be considered statistically significant.
Up to 1 year
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
|Veterans Adminstration New Jersey Health Care System||East Orange, New Jersey 07018-1095|
|Eastern Cooperative Oncology Group||Boston, Massachusetts 02215|