Zhu, Yehui
(2020)
Musculoskeletal Symptoms with Endocrine Therapy for Breast Cancer: Trajectory and Predictors.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Musculoskeletal symptoms (including arthralgias, myalgia, and muscle stiffness) are experienced by up to 85% of women undergoing aromatase inhibitor (AI) therapy for breast cancer, and are the number one contributor to the high treatment discontinuation rate. The purpose of this dissertation study was to examine the trajectories of musculoskeletal symptoms and related factors during the first 18 months of AI therapy for breast cancer. This is an ancillary study to a parent study, the Anastrozole Use in Menopausal Women (AIM). The AIM study provided data on pain, musculoskeletal symptoms, and candidate phenotypic factors for two cohorts of women (n=380) (cohort 1: women with early stage breast cancer who receive anastrozole; cohort 2: age- and education-matched women without cancer) at baseline (before initiation of AI therapy for breast cancer cohort), 6, 12, and 18 months after baseline. Based on the bio-banked DNA provided by a subgroup of participants (n=243), we genotyped 46 single nucleotide polymorphisms (SNPs) among the 25 candidate genes which were selected from a biological pathway analysis. Our results showed that a significant proportion of women experienced mild or moderate pain and musculoskeletal symptoms in a persistent or linearly increasing manner over the first 18 months of AI therapy. A profile of protective and risk factors across one or more phenotypes was identified. The protective phenotypic factors included older age, receipt of chemotherapy, older first menstrual period age, married/partnered, having an administrative level of occupation (vs unskilled/unemployed), having regular periods for most of one’s life, greater numbers of pregnancies, and having a history of tubal ligation. The phenotypic risk factors included receipt of AI therapy, greater anxiety, pain severity, depressive symptoms, fatigue at baseline, and having a history of arthritis, hysterectomy, or menopausal symptoms. A profile of protective and risk polymorphisms was identified. Variations in CYP19A1 (rs1008805) and NOS3 (rs1799983) were associated across phenotypes. The protective polymorphisms included BDNF rs6265, COMT rs4633 and rs887200, CXCL8 rs4073, ESR2 rs2772163, IL1B rs16944, RANKL rs1054016, VDR rs4516035 and rs731236. The risk polymorphisms included CYP19A1 rs1008805, CYP3A4 rs35599367, COMT rs165774, NOS3 rs1799983, OPG rs2073618, OPRM1 rs1799971, and TCL1A rs7158782 and rs7159713.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
20 February 2020 |
| Date Type: |
Publication |
| Defense Date: |
13 December 2019 |
| Approval Date: |
20 February 2020 |
| Submission Date: |
17 February 2020 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
133 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Nursing > Nursing |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
breast neoplasms, musculoskeletal pain, aromatase inhibitors, trajectory, predictor, gene |
| Date Deposited: |
20 Feb 2020 18:20 |
| Last Modified: |
20 Feb 2021 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38253 |
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