Postdiagnosis circulating osteoprotegerin and TRAIL concentrations and survival and recurrence after a breast cancer diagnosis: results from the MARIE patient cohort.

Background: Experimental studies suggest a role for osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in mammary tumor development and progression. These biomarkers have been minimally investigated with respect to outcomes in breast cancer patients.

Methods: OPG and TRAIL were evaluated in blood samples collected from 2459 breast cancer patients enrolled in the MARIE study, a prospective population-based patient cohort, at median of 129 days after diagnosis. Participants were between ages 50 and 74 at diagnosis and recruited from 2002 to 2005 in two regions of Germany. Follow-up for recurrence and mortality was conducted through June 2015. Delayed-entry Cox proportional hazards regression was used to assess associations between OPG and TRAIL with all-cause and breast cancer-specific mortality, and recurrence, both overall and by tumor hormone receptor status.

Results: Median follow-up time was 11.7 years, with 485 deaths reported (277 breast cancer-specific). Higher OPG concentrations were associated with a higher risk of all-cause mortality (hazard ratio for 1-unit log2-transformed concentration (HR_log2) = 1.24 (95% confidence interval 1.03-1.49). Associations were observed in women diagnosed with ER-PR- tumors or discordant hormone receptor status (ER-PR-, HR_log2 = 1.93 (1.20-3.10); discordant ERPR, 1.70 (1.03-2.81)), but not for women with ER + PR + tumors (HR_log2 = 1.06 (0.83-1.35)). OPG was associated with a higher risk of recurrence among women with ER-PR- disease (HR_log2 = 2.18 (1.39-3.40)). We observed no associations between OPG and breast cancer-specific survival, or for TRAIL and any outcome.

Conclusions: Higher circulating OPG may be a biomarker of a higher risk of poor outcome among women diagnosed with ER- breast cancer. Further mechanistic studies are warranted.