Review article
https://doi.org/10.20471/LO.2018.46.01.06
Hormone receptor expression and ribociclib activity in hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer
Eugen Javor
; Pharmacy Department, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
Lejsa Jakupović
; Pharmacy Department, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
Marko Skelin
; Pharmacy Department, General Hospital Šibenik, Šibenik, Croatia
Abstract
In the randomized, placebo-controlled, phase 3 MONALESSA-2 trial, in patients with hormone receptor positive (HR+) [the estrogen receptor (ER) and/or progesterone receptor (PR)] and human epidermal growth factor 2 receptor negative (HER2-) advanced breast cancer (BC), progression-free survival (PFS) was signifi cantly longer among those receiving ribociclib [cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor] plus letrozole compared to patients receiving placebo plus letrozole. Additionally, ER+/PR+ cohort demonstrated higher hazard ratio for PFS than ER+/PR- cohort (0.62 vs. 0.36). Evidence from cell-line models suggests that PR signaling is tightly linked to cell-cycle regulation in terms of inhibition of CDK 4/6 activity when exposed to progestin. A possible explanation of this fi nding may be that high PR expression could interfere with ribociclib activity on the cyclin-kinase level. Furthermore, it is questionable whether PR level determines the efficacy of ribociclib administration with higher levels of this receptor being predictive of ribociclib ineffi cacy. Considering the safety profile of ribociclib, it’s necessary to perform analysis of PFS among ER+/PR+ patients receiving ribociclib, to potentially assess the cut-off value of PR expression (or ER/PR ratio) as a predictive marker of CDK4/6 efficacy.
Keywords
ribociclib; breast cancer; hormone receptor expression
Hrčak ID:
204715
URI
Publication date:
20.7.2018.
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