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Effect of estradiol as a continuous variable on breast cancer survival by menopausal status: a cohort study in China

Abstract

High levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We evaluated the effect of E2 concentration on survival endpoints among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints. 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR 1.79, 95% CI 1.17–2.75, P = 0.008) and OS in post-menopausal women (HR 1.35, 95% CI 1.04–1.74, P = 0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation (“L-shaped” and “U-shaped”, respectively) with E2 levels. However, there was a linear relationship in post-menopausal women. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a “U-shaped” relationship with OS and PFS in pre-menopausal women. Pre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BMI:

Body mass index

CI:

Confidence intervals

E2:

Estradiol

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor-2

HIS:

Hospital information system

HR:

Hazard ratios

IHC:

Immunohistochemistry

OS:

Overall survival

PFS:

Progression-free survival

PR:

Progesterone receptor

TBCCC:

Tianjin Breast Cancer Cases Cohort

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Funding

This study was supported by the National Key Research and Development Program of China (Grant No. 2018YFC1315600), and National Natural Science Foundation of China (Grant Nos. 81974439, 81974488).

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Authors and Affiliations

Authors

Contributions

JL and CL designed the study, did the statistical analysis and drafted the manuscript. FS reviewed and revised the manuscript. All authors made contribution to the establishment of TBCCC and approved the final version.

Corresponding authors

Correspondence to Fengju Song or Kexin Chen.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The investigators in TBCCC obtained informed consent from each breast cancer patient and participants or their guardians. The current study was in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments and it was approved by the research ethics board of the Tianjin Medical University Cancer Institute and Hospital.

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Li, J., Li, C., Feng, Z. et al. Effect of estradiol as a continuous variable on breast cancer survival by menopausal status: a cohort study in China. Breast Cancer Res Treat 194, 103–111 (2022). https://doi.org/10.1007/s10549-022-06593-5

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  • DOI: https://doi.org/10.1007/s10549-022-06593-5

Keywords

  • Breast cancer
  • Estradiol
  • Survival
  • Menopause status
  • ER status