Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors Journal Article


Authors: Romero, S. A. D.; Su, H. I.; Satagopan, J.; Li, Q. S.; Seluzicki, C. M.; Dries, A.; DeMichele, A. M.; Mao, J. J.
Article Title: Clinical and genetic risk factors for aromatase inhibitor-associated arthralgia in breast cancer survivors
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). 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. 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). 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. © 2019 Elsevier Ltd
Keywords: adult; major clinical study; single nucleotide polymorphism; genetics; gene; breast cancer; inflammation; aromatase inhibitor; estrogen; risk factors; cancer survivor; arthralgia; adjuvant chemotherapy; cross-sectional study; genetic risk; menopause; postmenopause; caucasian; postmenopausal; breast neoplasm; college; human; female; priority journal; article; hsd17b2 gene
Journal Title: Breast
Volume: 49
ISSN: 0960-9776
Publisher: Elsevier Inc.  
Date Published: 2020-02-01
Start Page: 48
End Page: 54
Language: English
DOI: 10.1016/j.breast.2019.10.008
PUBMED: 31678641
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
Altmetric Score
MSK Authors
  1. Jun J Mao
    87 Mao
  2. Sally Ann Dominick Romero
    14 Romero
  3. Qing Susan Li
    25 Li