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Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors.
- Source :
-
Breast (Edinburgh, Scotland) [Breast] 2020 Feb; Vol. 49, pp. 48-54. Date of Electronic Publication: 2019 Oct 22. - Publication Year :
- 2020
-
Abstract
- Background: Arthralgia is a common and debilitating toxicity of aromatase inhibitors (AI) that leads to premature drug discontinuation. We sought to evaluate the clinical and genetic risk factors associated with AI-associated arthralgia (AIAA).<br />Methods: We performed a cross-sectional study among postmenopausal women with stage 0-III breast cancer who were prescribed a third-generation AI for adjuvant therapy. The primary outcome was patient-reported AIAA occurrence. We extracted and assayed germline DNA for single nucleotide polymorphisms (SNPs) of genes implicated in estrogen and inflammation pathways. Multivariable logistic regression models examined the association between demographic, clinical, and genetic factors and AIAA. Analyses were restricted to White participants.<br />Results: Among 1049 White participants, 543 (52%) reported AIAA. In multivariable analyses, women who had a college education [Adjusted Odds Ratio (AOR) 1.49, 95% Confidence Interval (CI) 1.00-2.20], had a more recent transition into menopause (<10 years) (5-10 years AOR 1.55, 95% CI 1.09-2.22; <5 years AOR 1.78, 95% CI 1.18-2.67), were within one year of starting AIs (AOR 1.61, 95% CI 1.08-2.40), and those who received chemotherapy (AOR 1.38, 95% CI 1.02-1.88) were significantly more likely to report AIAA. Additionally, SNP rs11648233 (HSD17B2) was significantly associated with higher odds of AIAA (AOR 2.21, 95% CI 1.55-3.16).<br />Conclusions: Time since menopause and start of AIs, prior chemotherapy, and SNP rs11648233 within the HSD17B2 gene in the estrogen pathway were significantly associated with patient-reported AIAA. These findings suggest that clinical and genetic factors involved in estrogen withdrawal increase the risk of AIAA in postmenopausal breast cancer survivors.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Aromatase Inhibitors therapeutic use
Arthralgia diagnosis
Arthralgia genetics
Breast Neoplasms genetics
Cross-Sectional Studies
Estradiol Dehydrogenases genetics
Female
Genetic Markers
Humans
Logistic Models
Middle Aged
Polymorphism, Single Nucleotide
Postmenopause
Risk Factors
Aromatase Inhibitors adverse effects
Arthralgia chemically induced
Breast Neoplasms drug therapy
Genetic Predisposition to Disease
Subjects
Details
- Language :
- English
- ISSN :
- 1532-3080
- Volume :
- 49
- Database :
- MEDLINE
- Journal :
- Breast (Edinburgh, Scotland)
- Publication Type :
- Academic Journal
- Accession number :
- 31678641
- Full Text :
- https://doi.org/10.1016/j.breast.2019.10.008