Climbing the RANKs.
The Study: Problem is, compared to a selective estrogen receptor modulator (SERM) like tamoxifen, AI increases risk of osteoporosis and subsequent fracture. In 2015, initial reporting of the primary endpoint of the phase 3 ABCSG-18 trial established that the RANKL inhibitor denosumab can help protect against bone fracture in this setting. Apparently, some take it a step further to postulate that RANKL inhibitors modify both the osseous and immunologic milieu such that they can even diminish risk of metastatic disease. Here we have the final results of the secondary outcome of disease-free survival (DFS). As a refresher, over 3400 women with early-stage hormone receptor-positive breast cancer receiving AI were randomized to the addition of  placebo versus  denosumab administered only every 6 months. And as you may have figured from the headline, DFS at 8 years was significantly improved with denosumab from 78 → 81%. In other words, a bigger discrepancy than that seen with AI over tamoxifen.
Bottom Line: There’s good evidence to add denosumab twice-yearly to aromatase inhibition for early-stage breast cancer to protect against fractures and even maximize DFS. | Gnant, Lancet Oncol 2019