Table 1 Overview of studies assessing the relationship between circulating concentrations of sRANKL or OPG and risk of breast cancer among healthy women without a BRCA mutation [28]
Author, Year | Study Source, Study Design, Sample Size | Sample Type | Study Aims | Follow-up | Population Size and Number of Cases | Results |
|---|---|---|---|---|---|---|
Vik et al., 2015 [39] | Tromsø Study Prospective cohort n = 3174 women (range 25–85 years) | Serum | To investigate the association between OPG and risk of breast cancer incident cancer in women | Median: 13.5 years | 76 incident breast cancers | RR total upper vs. lower tertile RR = 0.54; 95% CI 0.28–1.06; ptrend=0.07) RR > 60 years upper vs. lower tertile RR = 1.10; 95% CI 0.49–2.46; ptrend=0.84) RR < 60 years upper vs. lower tertile RR = 0.24; 95% CI 0.10–0.61; ptrend = 0.002) |
Fortner et al., 2017 [40] | EPIC cohort Nested case-control n = 2008 breast cancer cases matched 1:1 with healthy controls (pre- and post-menopausal women) | Serum | To investigate the association between circulating OPG and breast cancer risk by hormone receptor subtype | Baseline: 1992–2000 End of follow-up: 2003–2006 | 2008 incident invasive breast cancer cases (1622 ER+, 386 ER–) | Top vs. bottom tertile OPG RR ER– breast cancer = 1.93; 95% CI 1.24–3.02; ptrend = 0.03 Top vs. bottom tertile OPG RR ER+ breast cancer = 0.84; 95% CI 0.68–1.04; ptrend = 0.18 |
Kiechl et al., 2017 [41] | UKCTOCS, Bruneck cohorts and SUCCESS trial Case-control n = 278 postmenopausal women | Serum | To assess whether serum OPG and RANKL are associated with increased risk of developing breast cancer | Range (cases): 5–24 months Median (controls): 3.24 years | 98 breast cancer cases | OR breast cancer in high RANKL/OPG ratio and high progesterone group = 5.33; 95% CI 1.5–25.4; p = 0.02 |
Sarink et al., 2017 [42] | EPIC cohort Nested case-control n = 1976 incident invasive breast cancer matched 1:1 with healthy controls (median age at blood collection: 56 years (range 27–77 years)) | Serum | To investigate the association between serum sRANKL levels and breast cancer risk by hormone receptor subtype | Baseline: 1992–2000 End of follow-up: 2003–2006 | 1976 incident invasive breast cancer cases (1598 ER+) | Serum sRANKL associated with ER+ disease (5th vs. 1st quintile RR = 1.28; 95% CI 1.01–1.63; ptrend = 0.20) No association between serum sRANKL and ER– disease (5th vs. 1st quintile RR = 0.87; 95% CI 0.53–1.44; ptrend = 0.21) |
Kotsopoulos et al., 2020 [43] | NHS II Nested case-control study n = 297 incident invasive breast cancer (premenopausal women) matched 1:1 with healthy controls (median age at blood collection: 44 years (range 41–47 years)) | Plasma | To investigate the association between plasma OPG and breast cancer risk | Baseline: 1989–1990 End of follow-up: 2009 | 297 incident invasive breast cancer cases | No association between plasma OPG and breast cancer risk (highest vs. lowest quartile OR = 0.78; 95% CI 0.46–1.33; ptrend = 0.30) |