title: Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance.
abstract: OBJECTIVE
  Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity.
  
  
  METHODS
  Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05).
  
  
  RESULTS
  Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002).
  
  
  CONCLUSIONS
  Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.
authors.affiliation: State Department of Internal Medicine, Hippokration Hospital, Athens, Greece. ielefs@acn.gr
authors.forename: Ioannis S
authors.initials: IS
authors.lastname: Elefsiniotis
authors.forename: Konstantinos D
authors.initials: KD
authors.lastname: Pantazis
authors.forename: Anastasios
authors.initials: A
authors.lastname: Ilias
authors.forename: Loukas
authors.initials: L
authors.lastname: Pallis
authors.forename: Anargiros
authors.initials: A
authors.lastname: Mariolis
authors.forename: Irene
authors.initials: I
authors.lastname: Glynou
authors.forename: Helen
authors.initials: H
authors.lastname: Kada
authors.forename: Antonios
authors.initials: A
authors.lastname: Moulakakis
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005234:Fatty Liver / Q000139:chemically induced*; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000150:complications*; D005951:Glucose Tolerance Test; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D013629:Tamoxifen / Q000009:adverse effects*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen