Dataset Information

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

ABSTRACT: BACKGROUND:Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer. METHODS:This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group. RESULTS:Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients. CONCLUSIONS:Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.

SUBMITTER: Yoo JJ

PROVIDER: S-EPMC7392315 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

Yoo Jeong-Ju JJ Lim Yong Seok YS Kim Min Sung MS Lee Bora B Kim Bo-Yeon BY Kim Zisun Z Lee Ji Eun JE Lee Min Hee MH Kim Sang Gyune SG Kim Young Seok YS

PloS one 20200730 7

<h4>Background</h4>Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer.<h4>Methods</h4>This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 c ...[more]

PMID: 32730287

Similar Datasets

Project description:Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients.From an original observational study comprising 817 breast cancer patients, 99 women with operable breast cancer were retrospectively included in the present study. This cohort of patients were adjuvantly treated with tamoxifen, had provided serum samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3 years after the primary treatment commenced. The median follow-up time from this entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive, intermediate, and poor metabolizers). Tamoxifen and nine metabolites were quantified in serum (n?=?86) and compared with CYP2D6 phenotype groups and outcome.Breast cancer patients with low concentrations of Z-4-hydroxy-tamoxifen (Z-4OHtam; ??3.26 nM) had a breast cancer-specific survival (BCSS) of 60% compared to 84% in patients with Z-4OHtam concentrations?>?3.26 nM (p?=?0.020, log-rank hazard ratio (HR)?=?3.56, 95% confidence interval (CI)?=?1.14-11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels???9.00 nM BCSS was 57% compared to 84% for patients with concentrations?>?9.00 nM (p?=?0.029, HR?=?3.73, 95% CI?=?1.05-13.22). Low concentrations of Z-4OHtam and Z-endoxifen were associated with poorer survival also after adjusting for clinically relevant variables (HR?=?4.27, 95% CI?=?1.35-13.58, and HR?=?3.70, 95% CI?=?1.03-13.25, respectively). Overall survival analysis showed similar survival differences for both active metabolites. The Antiestrogen Activity Score showed comparable effects, but did not improve the prognostic information.Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00 nM, respectively, showed an adverse outcome. Our results suggest that direct measurement of active tamoxifen metabolite concentrations could be of clinical value. Validation in larger study cohorts is warranted.

Project description:PurposeTo determine the associations between ethnicity, age at diagnosis, obesity, multimorbidity, and odds of experiencing breast cancer (BC) treatment-related side effects among long-term Hispanic and non-Hispanic white (NHW) survivors from New Mexico and explore differences by tamoxifen use.MethodsLifestyle and clinical information including self-reported tamoxifen use and presence of treatment- related side effects were collected at follow-up interviews (12-15 years) for 194 BC survivors. Multivariable logistic regression models were used to examine associations between predictors and odds of experiencing side effects overall and by tamoxifen use.ResultsWomen ranged in age at diagnosis (30-74, M = 49.3, SD = 9.37), most were NHW (65.4%) and had in-situ or localized BC (63.4%). Less than half reportedly used tamoxifen (44.3%), of which 59.3% reported using > 5 years. Overall, survivors who were overweight/obese at follow-up were 5.42 times more likely to experience treatment-related pain (95% CI 1.40-21.0) compared to normal weight survivors. Survivors with multimorbidity, compared to survivors without, were more likely to report treatment-related sexual health issues (aOR 6.90, 95% CI 1.43-33.2) and poorer mental health (aOR 4.51, 95% CI 1.06-19.1). The statistical interactions between ethnicity and overweight/obese with tamoxifen use were significant (p-interaction < 0.05) for treatment-related sexual health issues.ConclusionOur results demonstrate that survivors with overweightness/obesity or multimorbidity may be more likely to experience BC treatment-related side effects. Tamoxifen use modifies associations between ethnicity, being overweight/obese, and sexual health issues following treatment. The likelihood of experiencing treatment-related side effects were more favorable for those on tamoxifen or those who had used tamoxifen for longer durations. These findings highlight the importance of fostering side effect awareness and applying appropriate interventions to assist with disease management throughout BC survivorship care.

Project description:BackgroundFour previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation.MethodsIn the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928.FindingsBetween April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8).InterpretationThese results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention.FundingCancer Research UK (UK) and the National Health and Medical Research Council (Australia).

Dataset Information

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

Publications

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets