Konference: 2010 35th Congress ESMO – účast ČR
Kategorie: Zhoubné nádory prsu
Téma: Breast Cancer, Early
Číslo abstraktu: 0266
Autoři: prof. MUDr. Luboš Petruželka, CSc.; MUDr. Soňa Argalacsová; Doc. MUDr. Ondřej Slanař, Ph.D.; doc. MUDr. Bohuslav Konopásek, CSc.; A. Drazdakova; A. Cerna; prof. MUDr. Tomáš Zima, DrSc., MBA
Introduction: TMX metabolism and convertion to active
endoxifen with 100-fold greater affinity to the ER is mainly
dependent on CYP2D6. Studies suggest endoxifen production is
reduced in patients (pts) with inactivated pms of CYP2D6 or pts
with comedication (comd) of potent CYP2D6 inhibitors. The role of
P-glycoprotein and pms of its gene MDR-1 has been unexplored
yet.
Methods: We evaluated the role of pms in CYP2D6 and MDR-1 in clinical outcome of premenopausal (premp) and postmenopausal (postmp) pts receiving TMX as adjuvant therapy in ER positive breast cancer. Genotype of CYP2D6 was detected by AmpliChip (Roche). Based on functional alleles we divided pts into groups with good function of CYP2D6 – Ultra-rapid (UrM) and efficient ( EM) metabolizers (mtbs) and group with impaired function of CYP2D6 – intermediate (IM) and poor (PM) mtbs. MDR-1 pms C3435T and G2677T/A were detected by PCR- RFLP. Comd with CYP2D6 inhibitors was also analyzed.
Results: We analyzed 81 postmp pts (median age 62,4 yrs) and 26 premp pts (med. age 46 yrs) receiving TMX since 1994. 31% premp and 35% postmp are still on TMX therapy. IM+PM was detected in 42 % premp and in 52% postmp pts. MDR-1 wild type CC3435 was detected in 32% premp and29 % postmp pts. C2677T of MDR-1 was detected 34% premp and 36 % postmp pts with wild type alelles. Comd with CYP2D6 inhibitors were noted in 23% of premp and 25% of postmp pts. Recurrence was seen in 7 premp pts (27%) with DFS 46,8 m and in 14 postmp pts (17.3%) with mDFS 30,7 m. In the group with recurrence on /after TMX therapy were inactivated pms of CYP2D6 ( IM+PM) detected in 42% of premp pts and in 50 % of postmp. Comd with CYP2D6 inhibitors we noted in and 14% of premp pts and in 28% postmp pts with disease reccurence.
Conclusion: Our preliminary results do not clearly support the hypothesis that the polymorphisms of CYP2D6, MDR-1 and the comedication with CYP2D6 inhibitors can influence the efficacy of TMX therapy.
Disclosure: All authors have declared no conflicts of interest.
Methods: We evaluated the role of pms in CYP2D6 and MDR-1 in clinical outcome of premenopausal (premp) and postmenopausal (postmp) pts receiving TMX as adjuvant therapy in ER positive breast cancer. Genotype of CYP2D6 was detected by AmpliChip (Roche). Based on functional alleles we divided pts into groups with good function of CYP2D6 – Ultra-rapid (UrM) and efficient ( EM) metabolizers (mtbs) and group with impaired function of CYP2D6 – intermediate (IM) and poor (PM) mtbs. MDR-1 pms C3435T and G2677T/A were detected by PCR- RFLP. Comd with CYP2D6 inhibitors was also analyzed.
Results: We analyzed 81 postmp pts (median age 62,4 yrs) and 26 premp pts (med. age 46 yrs) receiving TMX since 1994. 31% premp and 35% postmp are still on TMX therapy. IM+PM was detected in 42 % premp and in 52% postmp pts. MDR-1 wild type CC3435 was detected in 32% premp and29 % postmp pts. C2677T of MDR-1 was detected 34% premp and 36 % postmp pts with wild type alelles. Comd with CYP2D6 inhibitors were noted in 23% of premp and 25% of postmp pts. Recurrence was seen in 7 premp pts (27%) with DFS 46,8 m and in 14 postmp pts (17.3%) with mDFS 30,7 m. In the group with recurrence on /after TMX therapy were inactivated pms of CYP2D6 ( IM+PM) detected in 42% of premp pts and in 50 % of postmp. Comd with CYP2D6 inhibitors we noted in and 14% of premp pts and in 28% postmp pts with disease reccurence.
Conclusion: Our preliminary results do not clearly support the hypothesis that the polymorphisms of CYP2D6, MDR-1 and the comedication with CYP2D6 inhibitors can influence the efficacy of TMX therapy.
Disclosure: All authors have declared no conflicts of interest.
Datum přednesení příspěvku: 9. 9. 2010
