Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma - PubMed (original) (raw)

. 2017 Nov;15(11):1791-1799.

doi: 10.1016/j.cgh.2017.05.036. Epub 2017 Jun 1.

Gehan Botrus 2, Reham Abdel-Wahab 3, Robert A Wolff 2, Donghui Li 2, David Tweardy 4, Alexandria T Phan 5, Ernest Hawk 6, Milind Javle 2, Ju-Seog Lee 7, Harrys A Torres 8, Asif Rashid 9, Renato Lenzi 2, Hesham M Hassabo 2, Yasmin Abaza 2, Ahmed S Shalaby 2, Sahin Lacin 10, Jeffrey Morris 11, Yehuda Z Patt 12, Christopher I Amos 13, Saira A Khaderi 14, John A Goss 14, Prasun K Jalal 15, Ahmed O Kaseb 2

Affiliations

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

Manal M Hassan et al. Clin Gastroenterol Hepatol. 2017 Nov.

Abstract

Background & aims: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC.

Methods: We performed a case-control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC.

Results: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32-0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20-0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67-11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88-79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40-0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7-41.3 months) and 24.1 months for nonusers (95% CI, 19.02-29.30 months; P = .008).

Conclusion: In a case-control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.

Keywords: liver tumor; mortality; reduction; risk factor.

Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

The authors disclose no conflicts of interest.

Figures

Figure 1

Figure 1

Predicted mean age (years) at HCC onset and duration of estrogen use by linear regression; for example, the predicted mean ages at HCC onset at 6 years, 16 years, and 31 years of estrogen exposure were

Figure 2

Figure 2

(A) Median OS (95%CI) by estrogen use. (B) Univariate HRs (95% CI) of HCC prognostic factors. (C) Multivariate AHRs (95% CI) of estrogen use (.55, .40–.77) after adjusting for significant confounding factors of survival including race, hysterectomy, oophorectomy, multi-nodular tumor, cirrhosis, extra-hepatic metastasis, >50% liver involvement, AFP, vascular invasion, TNM staging, and treatment type.

Figure 2

Figure 2

(A) Median OS (95%CI) by estrogen use. (B) Univariate HRs (95% CI) of HCC prognostic factors. (C) Multivariate AHRs (95% CI) of estrogen use (.55, .40–.77) after adjusting for significant confounding factors of survival including race, hysterectomy, oophorectomy, multi-nodular tumor, cirrhosis, extra-hepatic metastasis, >50% liver involvement, AFP, vascular invasion, TNM staging, and treatment type.

Figure 2

Figure 2

(A) Median OS (95%CI) by estrogen use. (B) Univariate HRs (95% CI) of HCC prognostic factors. (C) Multivariate AHRs (95% CI) of estrogen use (.55, .40–.77) after adjusting for significant confounding factors of survival including race, hysterectomy, oophorectomy, multi-nodular tumor, cirrhosis, extra-hepatic metastasis, >50% liver involvement, AFP, vascular invasion, TNM staging, and treatment type.

References

    1. The Global Burden of Cancer 2013. JAMA Oncol. 2015 - PMC - PubMed
    1. Kew MC. Epidemiology of hepatocellular carcinoma in sub-Saharan Africa. Ann Hepatol. 2013;12:173–182. - PubMed
    1. El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004;127:S27–S34. - PubMed
    1. White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012. Gastroenterology. 152:812–820. - PMC - PubMed
    1. Hassan MM, Spitz MR, Thomas MB, El-Deeb AS, Glover KY, Nguyen NT, Chan W, Kaseb A, Curley SA, Vauthey JN, Ellis LM, Abdalla E, Lozano RD, Patt YZ, Brown TD, Abbruzzese JL, Li D. Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case-control study. Int J Cancer. 2008;123:1883–1891. - PMC - PubMed

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