Seventy percent of breast cancer express hormonal receptors and are treated with endocrine therapy, which targets mainly the estrogen receptor (ER) pathway. Progesterone receptor (PR) has also been explored as a therapeutic target and antiprogestins have been proposed to treat luminal breast carcinomas expressing higher levels of isoform A of PR (PRA) than isoform B (PRB). Since in luminal carcinomas the cyclin D1/RB/E2F cell cycle pathway is highly activated, CDK4/6 inhibitors are used to treat metastatic ER+/HER2- breast cancer in combination with endocrine therapy. However, resistant tumor cells may bypass the cell cycle inhibition through the activation of CDK2. Thus, CDK2 inhibitors in combination with endocrine therapy and/or CDK4/6 inhibitors may be an option to treat these tumors. Our study aims to evaluate the effect of two CDK2 inhibitors, Roscovitine (Rosco) and Dinaciclib in T47D cells which express both PR isoforms, and in the T47D variants that only express isoform PRA (T47D-YA) or PRB (T47D-YB), alone or in combination with the antiprogestin mifepristone. The three cell lines were similarly inhibited by Rosco with an IC50 of 12 µM. Rosco (5 and 10 µM) inhibited serum and hormone-induced T47D cell proliferation, with a decrease in ki-67 expression and RB phosphorylation (p<0.01). The combined treatment of Rosco (2 µM) and mifepristone (10 nM) was more efficient to inhibit cell proliferation only in T47D-YA cells (p<0.05). Dinaciclib (10 nM) inhibited the proliferation of T47D-YA and -YB cells (25% and 38% of inhibition respectively, p<0.01). The combined studies are in progress. We conclude that Roscovitine and Dinaciclib would be efficient to treat luminal breast carcinomas and the combination of mifepristone with Roscovitine may be a therapeutic option in tumors expressing higher levels of PRA than PRB.