Use of elevated bone turnover to predict bone metastasis

Abstract

591 Background: A favorable “soil” has been suggested as an important factor for the growth of cancer cells. In this study, the ability of pretreatment serum beta C-terminal telopeptide (B-CTx) of type I collagen, a marker of bone resorption, to predict breast cancer relapse in bone was investigated in a randomized adjuvant breast cancer trial. Methods: Serum B-CTx concentration (Serum CrossLaps, Nordic Biosciences, Copenhagen, DN) was determined in pretreatment serum from 621 of 667 primary breast cancer patients enrolled in the NCIC CTG MA.14 phase III adjuvant clinical trial of tamoxifen (20 mg po daily, 323 pts.) ± octreotide (90 mg mo. for 2 years, 298 pts.) which has recently had its final analysis. Stratification was by administration of adjuvant chemotherapy, axillary lymph node status, and ER and/or PR status. Recurrence-free survival (RFS) was a secondary endpoint defined as the time from randomization to the time of recurrence of the primary disease alone; the focus here was bone-only recurrence. Continuous serum B-CTx was added to the factors indicated by the main trial event-free survival (EFS) analyses; as well, we performed step-wise forward multivariate Cox regression adjusted for the stratification factors using continuous serum B-CTx. Results: At this time, 123/621 patients have had a recurrence: 19/621 (3.1%) with bone-only recurrence; and 66/621 (10.6%) with bone plus other sites of recurrence. Higher serum B-CTx was associated with shorter bone- only RFS (p=0.02). In a step-wise Cox multivariate model, the factors associated with shorter bone-only RFS metastasis were pathologic T (tumor size) (p=0.0004) and higher serum B-CTx (p = 0.04). Serum B-CTx was not associated with any other type of recurrence (p>0.05). Conclusions: Higher pretreatment serum B-CTx is a significant predictor of shorter recurrence-free survival for bone-only metastasis. Increased bone resorption creates an environment that promotes the growth of breast cancer cells. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis