High Serum Estradiol Reduces Acute Hepatotoxicity Risk Induced by Epirubicin Plus Cyclophosphamide Chemotherapy in Premenopausal Women with Breast Cancer

Abstract

Aim: We evaluated whether acute drug-induced liver injury (DILI) caused by adjuvant chemotherapy with epirubicin plus cyclophosphamide for early breast cancer was associated with estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH).Methods: Reproductive hormone test results of breast cancer patients were collected in the first chemotherapy cycle. E2, LH, and FSH levels were loge-transformed to normally distributed variables and were assessed using Student’s t-test to determine significant differences between the case and control groups. Hormone levels were classified according to the interquartile range and analyzed by logistic regression to determine their association with DILI caused by chemotherapy.Results: Among the 915 enrolled patients (DILI group: 204; control group: 711), menopausal status, along with serum E2, LH, and FSH levels, did not substantially differ between case and control groups. However, in the premenopause subgroup (n = 483), we found a significant difference in the E2 level between the case and control groups (p = 0.001). After adjusting for age and body mass index, premenopausal patients with 152–2,813 pg/mL E2 showed a lower risk of chemotherapy-induced DILI than patients with ≤20 pg/mL E2 (odds ratio: 0.394; 95% confidence interval: 0.207–0.748). The linear trend χ2 test revealed that E2 levels in premenopausal patients with breast cancer were inversely associated with the development of DILI.Conclusion: High serum E2 levels are associated with a reduced DILI risk in premenopausal patients with breast cancer undergoing epirubicin plus cyclophosphamide adjuvant chemotherapy.

A computable biomedical knowledge system: Toward rapidly building candidate‐directed acyclic graphs

“…This may result in a reduced therapeutic efficacy of cyclophosphamide. Estradiol has the ability to improve liver function by promoting the production of anti‐inflammatory cytokines 20,21 . Figure 6 illustrates the bidirectional interaction between estradiol and cyclophosphamide.…”

Protective Effect of Scent Leaves (Ocimum Gratissimum) and Pawpaw Seeds (Carica Papaya) Aqueous Extract on Carbon Tetrachloride (CCl4) Administered in Male Albino Wistar Rats

“…Estradiol is essential for modulating libido, erectile function, and spermatogenesis (Schulster et al, 2016) while testosterone is the male sex hormone that is made in the testicles and its levels are important to normal male sexual development and functions. Also, studies have reported that estradiol level is linked with liver injury as high estradiol level reduces hepatotoxicity (Akene 2021;Huang et al, 2021). Exposure to CCl 4 has also been reported to induce liver and kidney damage in rats group showed focal tubular necrosis, vascular stenosis and heavy interstitial infiltrates of inflammatory cells in histopathology study (Dong et al, 2016, Okerulu et al, 2018Ehimigbai,and Imariebe 2022).…”

Estradiol Levels and Chemotherapy in Breast Cancer Patients: A Prospective Clinical Study

“…The mechanism may be related to the activation of proteins, enzymes, or oncogenes involved in nucleic acid synthesis induced by these hormones, thereby promoting the growth of cancer cells. However, in the study from Huang et al, it was found that high serum E2 levels were associated with reduced risk of drug-induced liver injury (DILI) in premenopausal breast cancer patients who underwent epirubicin regimen chemotherapy with cyclophosphamide adjuvant chemotherapy [ 16 , 17 ].…”