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Hormone replacement therapy and breast cancer survival: a systematic review and meta-analysis of observational studies

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Abstract

Previous studies on the association between hormone replacement therapy (HRT) and breast cancer survival have yielded mixed results. We aimed to perform a meta-analysis to assess the association with all available studies. Relevant studies were identified by searching PubMed and EMBASE to April 2017. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. The dose–response relationship was assessed by random-effects meta-analysis and dose–response meta-regression models. Forty cohort studies and two case–control studies involving 1,756,833 participants were included. The results showed that prediagnosis HRT use was associated with decreased risk of dying from breast cancer (HR = 0.88, 95% CI 0.81–0.97) or any cause (HR = 0.79, 95% CI 0.69–0.90). Postdiagnosis HRT use also showed a beneficial effect on breast cancer survival. In the subgroup analyses, we found that patients who were current users at diagnosis or who received combined hormone therapy before diagnosis seemed to show more benefit from HRT use. In dose–response analysis, we observed a linear relationship between prediagnosis HRT and breast cancer-specific mortality and a 1-year increment in duration of exposure to HRT conferred an HR of 0.99 (95% CI 0.98–1.00) for death from breast cancer. In conclusion, the average effect of HRT use seems not harmful to breast cancer survival. Nevertheless, this effect of HRT use is needed for further assessment.

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  1. Xinnian Yu and Siying Zhou: equal contributors.

Authors and Affiliations

  1. Department of Internal Medicine, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China

    Xinnian Yu

  2. Department of Internal Medicine, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, China

    Xinnian Yu

  3. The First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing, 210023, China

    Siying Zhou

  4. Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, China

    Jinyan Wang, Qian Zhang, Junchen Hou, Lingping Zhu & Yunjie He

  5. Center of Clinical Laboratory Science, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China

    Jianhua Zhao & Shanliang Zhong

  6. Center of Clinical Laboratory Science, Nanjing Medical University Affiliated Cancer Hospital, Baiziting 42, Nanjing, 210009, China

    Jianhua Zhao & Shanliang Zhong

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This study was funded by the National Natural Science Foundation of China (81602551).

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12282_2017_789_MOESM1_ESM.tif

Funnel plot of studies on hormone replacement therapy before diagnosis and all-cause mortality of breast cancer patients. The solid line in the center is the natural logarithm of pooled relative risk, and two oblique dotted lines are pseudo 95% CIs. Closed circles indicate the estimates of each individual study. Open circles indicate the estimates of the potential missing studies according to the trim-and-fill method. (TIFF 173 kb)

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Yu, X., Zhou, S., Wang, J. et al. Hormone replacement therapy and breast cancer survival: a systematic review and meta-analysis of observational studies. Breast Cancer 24, 643–657 (2017). https://doi.org/10.1007/s12282-017-0789-5

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