Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes

Abstract

Anastrozole is a selective non-steroidal aromatase inhibitor that blocks the conversion of androgens to estrogens in peripheral tissues. It is used as adjuvant therapy for early-stage hormone-sensitive breast cancer in postmenopausal women. Significant side effects of anastrozole include osteoporosis and increased levels of cholesterol. To date, seven case reports on anastrozole hepatotoxicity have been published. We report the case of an 81-year-old woman with a history of breast cancer, arterial hypertension, type 2 diabetes mellitus, hyperlipidemia, and chronic renal insufficiency. Four days after switching hormone therapy from tamoxifen to anastrozole, icterus developed along with a significant increase in liver enzymes (measured in the blood). The patient was admitted to hospital, where a differential diagnosis of jaundice was made and anastrozole was withdrawn. Subsequently, hepatic functions quickly normalized. The observed liver injury was attributed to anastrozole since other possible causes of jaundice were excluded. However, concomitant pharmacotherapy could have contributed to the development of jaundice and hepatotoxicity, after switching from tamoxifen to anastrozole since several the patient’s medications were capable of inhibiting hepatobiliary transport of bilirubin, bile acids, and metabolized drugs through inhibition of ATP-binding cassette proteins. Telmisartan, tamoxifen, and metformin all block bile salt efflux pumps. The efflux function of multidrug resistance protein 2 is known to be reduced by telmisartan and tamoxifen and breast cancer resistance protein is known to be inhibited by telmisartan and amlodipine. Moreover, the activity of P-glycoprotein transporters are known to be decreased by telmisartan, amlodipine, gliquidone, as well as the previously administered tamoxifen. Finally, the role of genetic polymorphisms of cytochrome P450 enzymes and/or drug transporters cannot be ruled out since the patient was not tested for polymorphisms.

Drug‐induced liver injury as assessed by the updated Roussel Uclaf Causality Assessment Method following mild COVID‐19 in a patient under anastrozole therapy—A case report

“…Anastrozole-induced hepatotoxicity is a rare event and if it manifests, it does so within the first few months of starting this medication. [3][4][5][6] Therefore, DILI caused by toxic or immunological mechanisms is usually not expected to appear with a latency of 15 years of medical drug consumption. No changes in our patient's habits or diet have occurred and no new dietary supplements or herbal drugs have been introduced.…”

“…Anastrozole‐induced hepatotoxicity is a rare event and if it manifests, it does so within the first few months of starting this medication 3–6 . Therefore, DILI caused by toxic or immunological mechanisms is usually not expected to appear with a latency of 15 years of medical drug consumption.…”

“…The major side effects include osteoporosis, hypercholesterolemia, and musculoskeletal events, such as arthralgia and myalgia 2 . Other adverse events are rare, including symptoms of acne, masculinization, and drug‐induced liver injury (DILI), with the latter reported in a few cases only 3–6 …”

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

“…Publication details of new iDILI cases by known drugs were informative. Such cases now present RUCAM-based causality associated with individual causality gradings and a selection of implicated drugs listed in alphabetical order [ 3 ]: amlodipine (RUCAM score 6, probable causality grading) [ 13 ], anastrozole (score 6, probable) [ 14 ], atorvastatin (score 9, highly probable) [ 15 ], atovaquone (score 9, highly probable) [ 16 ], candesartan (score 8, probable) [ 17 ], ciprofloxacin (score 11, highly probable) [ 18 ], fenofibrate (score 10, highly probable) [ 19 ], flucloxacillin (score 8, probable) [ 20 ], gemcitabine (score 10, highly probable) [ 21 ], infliximab (score 10, highly probable) [ 22 ], metamizole (median score 7, probable) [ 23 ], and teriflunomide (score 8, probable) [ 24 ]. Probable and highly probable RUCAM-based causality gradings commonly reflect complete case data sets by early prospective collection of the required clinical and laboratory data [ 3 ] in line with previous recommendations [ 6 ].…”

Association of Hypertension and Breast Cancer: Antihypertensive Drugs as an Effective Adjunctive in Breast Cancer Therapy

“…Researchers have examined that the prevalence of hypertension and female breast cancer is on the rise with age and consider postmenopausal estrogen withdrawal as one of the possible reasons for this escalation. 30 , 31 It has also been proposed that as BC and HTN share common pathophysiology pathways mediated by fatty tissue, it is the factor that may lead to chronic inflammation and BC onset. 32 Another possible justification of this association lies in the role of HTN in inhibiting the inflammation and increasing the apoptosis, which may lead to the development of BC in breast tissues 33 ?…”