Table 2 Summary of studies assessing the relationship between circulating concentrations of sRANKL and/or OPG and risk of breast cancer among BRCA1 and BRCA2 mutation carriers [28]

Widschwendter et al., 2015 [30]

UKFOCSS

Cross-sectional

n = 391 BRCA1/2 mutation carriers and 782 healthy controls (> 35 years)

To evaluate the relationship between the BRCA1/2 mutation and levels of sRANKL and OPG

To assess the relationship between reported breast cancer risk associated with the nucleotide position of the BRCA1/2 germline mutation and serum OPG concentrations

N/A

N/A

Lower serum OPG and sRANKL levels in BRCA1/2 mutation carriers vs. healthy controls

Germline BRCA1/2 mutation locations known to confer an increased risk of breast cancer were associated with lower OPG levels

Odén et al., 2016 [44]

Risk Factor Analysis of Hereditary Breast and Ovarian Cancer

Prospective cohort

n = 206 BRCA1/2 mutation carriers between 18 and 70 years

To assess whether plasma OPG levels contribute to breast cancer risk in BRCA1/2 mutation carriers

Mean: 6.5 years (0.1–18.8 years)

18 incident breast cancer cases

High vs. low OPG HR breast cancer = 0.25 (95% CI 0.08–0.78), p = 0.02

Zaman et al., 2019 [45]

Risk Factor Analysis of Hereditary Breast and Ovarian Cancer

Prospective cohort

n = 184 BRCA1/2 mutation carriers between 18 and 80 years

To investigate the association between plasma RANKL levels and breast cancer risk in BRCA1/2 mutation carriers

Mean: 6.3 years (0.02–19.24 years)

15 incident breast cancer cases

High vs. low RANKL HR breast cancer = 1.06 (95% CI 0.34–3.28), p = 0.86