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CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8.


ABSTRACT: PURPOSE:Controversy exists about CYP2D6 genotype and tamoxifen efficacy. EXPERIMENTAL DESIGN:A matched case-control study was conducted using the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG8) that randomized postmenopausal women with estrogen receptor (ER)-positive breast cancer to tamoxifen for 5 years (arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (arm B). Cases had disease recurrence, contralateral breast cancer, second non-breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and tumor-node-metastasis (TNM) stage. Genotyping was conducted for alleles associated with no (PM; *3, *4, *6), reduced (IM; *10, and *41), and extensive (EM: absence of these alleles) CYP2D6 metabolism. RESULTS:The common CYP2D6*4 allele was in Hardy-Weinberg equilibrium. In arm A during the first 5 years of therapy, women with two poor alleles [PM/PM: OR, 2.45; 95% confidence interval (CI), 1.05-5.73, P = 0.04] and women with one poor allele (PM/IM or PM/EM: OR, 1.67; 95% CI, 0.95-2.93; P = 0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3 to 5 when patients remained on tamoxifen (arm A) or switched to anastrozole (arm B), PM/PM tended toward a higher likelihood of a disease event relative to EM/EM (OR, 2.40; 95% CI, 0.86-6.66; P = 0.09) among women on arm A but not among women on arm B (OR, 0.28; 95% CI, 0.03-2.30). CONCLUSION:In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration and not after switching to anastrozole.

SUBMITTER: Goetz MP 

PROVIDER: S-EPMC3548984 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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CYP2D6 metabolism and patient outcome in the Austrian Breast and Colorectal Cancer Study Group trial (ABCSG) 8.

Goetz Matthew P MP   Suman Vera J VJ   Hoskin Tanya L TL   Gnant Michael M   Filipits Martin M   Safgren Stephanie L SL   Kuffel Mary M   Jakesz Raimund R   Rudas Margaretha M   Greil Richard R   Dietze Otto O   Lang Alois A   Offner Felix F   Reynolds Carol A CA   Weinshilboum Richard M RM   Ames Matthew M MM   Ingle James N JN  

Clinical cancer research : an official journal of the American Association for Cancer Research 20121204 2


<h4>Purpose</h4>Controversy exists about CYP2D6 genotype and tamoxifen efficacy.<h4>Experimental design</h4>A matched case-control study was conducted using the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG8) that randomized postmenopausal women with estrogen receptor (ER)-positive breast cancer to tamoxifen for 5 years (arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (arm B). Cases had disease recurrence, contralateral breast cancer, second non-breast canc  ...[more]

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