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Breast Cancer Res Treat (2010) 121:789791 DOI 10.1007/s10549-009-0576-x
BRIEF REPORT
Severe prolonged cholestatic hepatitis caused by exemestane
Ting Bao John Fetting Laura Mumford
Jane Zorzi Karineh Shahverdi Stacie Jeter
Frank Herlong Vered Stearns Linda Lee
Received: 30 September 2009 / Accepted: 2 October 2009 / Published online: 16 October 2009 Springer Science+Business Media, LLC. 2009
Aromatase inhibitors (AIs) are used as rst-line adjuvant hormonal therapy in postmenopausal women with hormone receptor-positive breast cancer, either as monotherapy or sequential therapy after tamoxifen [16]. Unlike tamoxifen, the former gold standard adjuvant hormonal therapy, AIs cause musculoskeletal symptoms, osteoporosis, and bone fractures [16]. Although AIs such as letrozole and anastrozole also cause liver enzyme elevation unrelated to liver metastasis in 35% patients,1,2 severe hepatotoxicity has rarely been associated with AIs. We report a case of severe prolonged cholestatic hepatitis caused by exemestane.
Case report
A 47-year-old postmenopausal white, non-Hispanic woman with no signicant past medical history was diagnosed with stage I (T1a, N0, M0) breast cancer. The tumor was a 4 mm, ER positive, PR weakly positive, HER2 negative, Ki67 1%, grade I inltrating ductal carcinoma for which she underwent lumpectomy with sentinel lymph node biopsy. She had no known drug allergies and was taking only naproxen 550 mg orally, about thrice a week due to sports-related wrist discomfort. She consumed no alcohol
and did not use any nutritional or dietary supplements. Given a strong family history of breast cancer and conrmed postmenopausal status, the patient was enrolled in a clinical trial in which women were randomized to the AI exemestane or letrozole to assess pharmacogenetics endpoints. She was randomized to and initiated exemestane 25 mg daily. Her baseline laboratory parameters, including cell counts and chemistry panel, were all within normal limits.
Three weeks after initiating exemestane, the patient reported fatigue, jaundice, and pruritis, associated with elevated total bilirubin, aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) (Table 1). Hepatitis serologic tests, including hepatitis A IgM, hepatitis B surface antigen, hepatitis B core IgM, and hepatitis C antibody, were negative. Autoanti-bodies associated with autoimmune hepatitis, including antimitochondrial antibody (AMA) and antinuclear antibody (ANA), were also negative. Exemestane was discontinued.
Three weeks following exemestane discontinuation, the serum total bilirubin was 16.2 mg/dl with stabilization of...