Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment.
OBJECTIVE
The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy.


METHODS
A total of 493 patients of the Austrian TIGER study receiving adjuvant tamoxifen therapy were studied for this pharmacogenetic interaction. All women with estrogen receptor positive tumors and tamoxifen therapy longer than 6 months were genotyped for CYP2D6*4 using TaqMan technology. Time to tumor progression, defined as local, regional, distant recurrence or contralateral breast cancer and progression free survival, was analyzed.


RESULTS
No significant difference in time to tumor progression or progression free survival between the CYP2D6*4 genotype groups in the overall study cohort was found. In a subgroup of patients treated with chemotherapy the CYP2D6*4 poor metabolizers had a tendency towards a shorter mean time to progression. In this group the mean time to tumor progression and the progression free survival were 1.0 years in the CYP2D6*4/*4 group, 6.3 years in the *1/*4 group and 4.97 years in the *1/*1 group (Wilcoxon p = 0.104).


CONCLUSIONS
While earlier data on CYP2D6 and tamoxifen excluded women with prior chemotherapy, the present analysis suggests that CYP2D6*4 genotype might be particularly crucial in this group of high-risk patients. Key limitations are restriction to the CYP2D6*4 allele and missing data of comedication.
Stingl
Julia Carolin
JC
Institute of Pharmacology of Natural Compounds and Clinical Pharmacology, University Ulm, Germany.
Parmar
Sumit
S
Huber-Wechselberger
Ariana
A
Kainz
Alexander
A
Renner
Wilfried
W
Seeringer
Angela
A
Brockmöller
Jürgen
J
Langsenlehner
Uwe
U
Krippl
Peter
P
Haschke-Becher
Elisabeth
E
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001317:Austria; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6