Hematological and biochemical markers influencing breast cancer risk and mortality: Prospective cohort study in the UK Biobank by multi-state models.

BACKGROUND

Breast cancer is the most common cancer and the leading cause of cancer-related death among women. However, evidence concerning hematological and biochemical markers influencing the natural history of breast cancer from in situ breast cancer to mortality is limited.

METHODS

In the UK Biobank cohort, 260,079 women were enrolled during 2006-2010 and were followed up until 2019 to test the 59 hematological and biochemical markers associated with breast cancer risk and mortality. The strengths of these associations were evaluated using the multivariable Cox regression models. To understand the natural history of breast cancer, multi-state survival models were further applied to examine the effects of biomarkers on transitions between different states of breast cancer.

RESULTS

Eleven biomarkers were found to be significantly associated with the risk of invasive breast cancer, including mainly inflammatory-related biomarkers and endogenous hormones, while serum testosterone was also associated with the risk of in-situ breast cancer. Among them, C-reactive protein (CRP) was more likely to be associated with invasive breast cancer and its transition to death from breast cancer (HR for the highest quartile = 1.46, 95 % CI = 1.07-1.97), while testosterone and insulin-like growth factor-1 (IGF-1) were more likely to impact the early state of breast cancer development (Testosterone: HR for the highest quartile = 1.31, 95 % CI = 1.12-1.53; IGF-1: HR for the highest quartile = 1.17, 95 % CI = 1.00-1.38).

CONCLUSION

Serum CRP, testosterone, and IGF-1 have different impacts on the transitions of different breast cancer states, confirming the role of chronic inflammation and endogenous hormones in breast cancer progression. This study further highlights the need of closer surveillance for these biomarkers during the breast cancer development course.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf. HY reports receiving research funding from the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province and Fujian Medical University, outside the submitted work. KC reports receiving research funding from the Swedish Research Council and Swedish Cancer Society, outside the submitted work. WH reports receiving research funding from Zhejiang University, outside the submitted work. All other authors declare no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.