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Aromatase Inhibitors and Newly Developed Nonalcoholic Fatty Liver Disease in Postmenopausal Patients with Early Breast Cancer: A Propensity Score-Matched Cohort Study

 Jung Il Lee  ;  Jung‐Hwan Yu  ;  Sung Gwe Anh  ;  Hyun Woong Lee  ;  Joon Jeong  ;  Kwan Sik Lee 
 ONCOLOGIST, Vol.24(8) : e653-e661, 2019 
Journal Title
Issue Date
Aromatase inhibitors ; Breast cancer ; Estrogen ; Menopause ; Nonalcoholic fatty liver disease
BACKGROUND: Unlike tamoxifen, the relationship between aromatase inhibitor use in postmenopausal patients with breast cancer and nonalcoholic fatty liver disease (NAFLD) has not been delineated.

MATERIALS AND METHODS: A retrospective analysis of 253 patients with early breast cancer without baseline NAFLD and treated with nonsteroidal aromatase inhibitors was performed. Among them, 220 patients were matched for sex, age, and menstruation status with healthy patients, and the prevalence of NAFLD was compared. NAFLD was determined by hepatic steatosis index in the absence of other known liver diseases. The presence of significant liver fibrosis in patients with NAFLD was determined noninvasively by AST-platelet ratio index, FIB-4 score, and NAFLD fibrosis score (NFS).

RESULTS: Postmenopausal patients with breast cancer undergoing treatment with aromatase inhibitors had higher prevalence of NAFLD independent of body mass index (BMI) and underlying diabetes mellitus (DM). Although the aromatase inhibitor group showed higher fibrotic burden by NFS, independent of BMI and DM, the proportion of advanced fibrosis did not show statistically significant differences between AI-treated patients and the healthy patients. Those with abnormal baseline fasting glucose levels are suggested to have increased risk of NAFLD development after aromatase inhibitor treatment. In addition, patients with NAFLD developed after aromatase inhibitor use had significantly lower disease-free survival than those without NAFLD, although there was no significant difference in overall survival.

CONCLUSION: Results of this study suggest that inhibition of estrogen synthesis in postmenopausal women undergoing treatment with aromatase inhibitors could increase the risk of NAFLD, which might have some influence on the prognosis of patients with breast cancer.

IMPLICATIONS FOR PRACTICE: Unlike tamoxifen, the role of aromatase inhibitor treatment use in postmenopausal patients with breast cancer in development of fatty liver is not well known. In this propensity-matched cohort study, postmenopausal patients with breast cancer treated with aromatase inhibitors had increased risk of nonalcoholic fatty liver disease compared with healthy women after menopause, independent of obesity and diabetes mellitus. The results show possible adverse influence of the newly developed fatty liver on breast cancer disease-free survival and suggest a necessity for further validation. Fatty liver may need to be considered as an adverse event for aromatase inhibitor treatment.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Sung Gwe(안성귀) ORCID logo https://orcid.org/0000-0002-8778-9686
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Lee, Jung Il(이정일) ORCID logo https://orcid.org/0000-0002-0142-1398
Lee, Hyun Woong(이현웅) ORCID logo https://orcid.org/0000-0002-6958-3035
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
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