COMBINATION OF PALBOCICLIB WITH ANTIPROGESTINS IN EXPERIMENTAL BREAST CANCER MODELS WITH DIFFERENT PROGESTERONE RECEPTOR ISOFORM RATIOS

PATACCINI, GABRIELA; SEQUEIRA, GONZALO; VANZULLI, SILVIA; LANARI, CLAUDIA; GIULIANELLI, SEBASTIÁN

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

SAIC

Luminal breast cancers represent morethan 70% of all breast cancer patients and they are susceptibleto an endocrine therapy. Palbociclib (PALBO), an oral CDK 4/6inhibitor, is currently used in combination with endocrine therapyto treat advanced hormone receptor-positive breast cancer.However with time almost all patients acquire resistance.Therefore, alternative therapies are required to reduce breastcancer mortality. We have recently reported that breast cancerpatients with tumors expressing higher levels of isoform A of theprogesterone receptor (PRA) than isoform B (PRB) may benefitfrom an antiprogestin treatment. The aim of this study was toevaluate the effect of PALBO in combination with theantirpogestin mifepristone (MFP) in luminal experimental breastcancer models. We first tested the effects of MFP (10 nM) and/orPALBO (100 nM) on cell proliferation in human T47D cells and inT47D-YA and T47D-YB cells expressing only PRA or PRBrespectively. Cells were incubated in the presence of 5 % steroidstripped fetal calf serum and FGF2 (50 ng/ml) to have a basalhigh proliferative state. T47D and T47D-YA FGF2-treated cellswere inhibited by MFP, or PALBO (p