A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)
Overview
- Phase
- N/A
- Intervention
- anastrozole
- Conditions
- Estrogen Receptor-positive Breast Cancer
- Sponsor
- ECOG-ACRIN Cancer Research Group
- Enrollment
- 1046
- Locations
- 2
- Primary Endpoint
- Associations Between Pre-specified Single Nucleotide Polymorphisms (SNPs) and Discontinuation of Treatment With Aromatase Inhibitor (AI) Due to the Development of Musculoskeletal Symptoms (MSS)
- Status
- Active, Not Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
E1Z11 is a study to determine whether certain genetic information can predict which breast cancer patients will discontinue treatment with aromatase inhibitors (AIs) due to the development of musculoskeletal symptoms (MSS). Women with stage I-III breast cancer who are prescribed the aromatase inhibitor anastrozole as treatment may join.
Detailed Description
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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 with AIs. 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 anastrozole. VIII. To collect serum samples for future testing for biomarkers of AIMSS. OUTLINE: Patients receive anastrozole orally (PO) once daily (QD) for 12 months. After the completion of study treatment, patients are followed up for 12 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be post-menopausal; post-menopausal will be defined as women meeting any of the following criteria:
- •\>= 60 years of age; or
- •\< 60 years of age and amenorrheic for \>= 12 months prior to day 1 if uterus/ovaries are intact; or
- •\< 60 years of age, and the last menstrual period 6-12 months prior to day 1, if intact uterus/ovaries and meets biochemical criteria for menopause (follicle-stimulating hormone \[FSH\] and estradiol within institutional standard for postmenopausal status); or
- •\< 60 years of age, without a uterus, and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or
- •\< 60 years of age and history of bilateral oophorectomy; surgery must have been completed at least 4 weeks prior to day 1; or
- •Prior radiation castration with amenorrhea for at least 6 months
- •Patients must have estrogen and/or progesterone receptor positive histologically confirmed stage I-III adenocarcinoma of the breast
- •Patients must have completed recommended local therapy and adjuvant chemotherapy for breast cancer
- •Plan to treat with anastrozole for at least 12 months
Exclusion Criteria
- •Prior AI therapy with exemestane, letrozole, or anastrozole as adjuvant therapy or for prevention of breast cancer; prior tamoxifen as adjuvant therapy or for prevention is allowed
- •Patients must not be currently taking (or have taken in the past 6 months) ongoing, daily analgesic medication for active, chronic conditions (i.e., rheumatoid arthritis, carpal tunnel syndrome, tenosynovitis, systemic lupus erythematosus, gout, fibromyalgia, or severe osteoarthritis involving the hands, wrists, hips, knees, feet or ankles); (note: patients taking daily low dose aspirin are allowed to participate in this trial)
- •Prior history of deep vein thrombosis (DVT) or pulmonary embolism in the past 5 years
Arms & Interventions
Supportive care (anastrozole)
Patients receive anastrozole PO QD for 12 months.
Intervention: anastrozole
Outcomes
Primary Outcomes
Associations Between Pre-specified Single Nucleotide Polymorphisms (SNPs) and Discontinuation of Treatment With Aromatase Inhibitor (AI) Due to the Development of Musculoskeletal Symptoms (MSS)
Time Frame: Assessed at baseline and 3, 6, 9, 12 months
Patients were classified into two groups based on whether or not they discontinued treatment due to MSS within 12 months. The 10 SNPs evaluated include ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). The associations between SNPs and discontinuation of treatment due to AIMSS are presented by odds ratios (ORs). An OR of 1 suggests no association, while an OR \> 1 indicates a greater chance of treatment discontinuation in the one group compared to the reference group, and an OR \< 1 suggests a lower chance.
Secondary Outcomes
- Associations Between Development of Other Potential Complications of AI Therapy and Other SNPs in CYP, UGT, Vitamin D, Serotonin and Other Receptors(Assessed at baseline, and 3, 6, 9, 12 months)
- Associations Between Other SNPs in CYP, UGT, Vitamin D, Serotonin and Other Receptors and Discontinuation of Treatment Due to the Development of Severe AIMSS(Assessed at baseline and 3, 6, 9, 12 months)
- The Distribution of the Development of AIMSS by Genotype of the rs2296972 SNP(Assessed at baseline, and 3, 6, 9, 12 months)
- The Distribution of Development of AIMSS by Race(Assessed at baseline, and 3, 6, 9, 12 months)
- Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at Baseline for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).(Assessed at baseline)
- Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 3 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).(Assessed at 3 months)
- Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 6 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).(Assessed at 6 months)
- Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 9 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).(Assessed at 9 months)
- Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 12 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).(Assessed at 12 months)
- 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 Anastrozole(Assessed at baseline, diagnosis of AIMSS, discontinuation of treatment due to AIMSS, one month after treatment discontinuation due to AIMSS, and 3, 6, 9, 12 months)