Table 4.

Optimization of Endocrine Therapy

Current Study		ATAC Trial
CYP2D6 Stratificationa	Hazard Ratio (95% CI)b	Treatment Mode	Hazard Ratio (95% CI)c	P Valued
Time to Recurrence
EM	1 [Reference]	Aromatase inhibitors	1 [Reference]	.19
hetEM/IM	1.40 (1.04–1.90)	Tamoxifen	1.31 (1.15–1.49)	.01
PM	2.12 (1.10–3.28)			.11
Decreased	1.57 (1.18–2.08)
Event-Free Survivale
EM	1 [Reference]	Aromatase inhibitors	1 [Reference]
Decreased	1.35 (1.08–1.68)	Tamoxifen	1.18 (1.06–1.31)	.10

Abbreviations: CI, confidence interval; CYP, cytochrome P450; EM, extensive metabolism; IM, intermediate metabolism; PM, poor metabolism; UM, ultrarapid metabolism.

^aCYP2D6 phenotypes are defined as EM with 2 functional alleles (EM/EM, including UM), hetEM/IM with intermediate or 1 poor metabolism alleles (EM/IM, EM/PM, IM/IM, or IM/PM), and PM homozygous for poor metabolism alleles (PM/PM). Decreased refers to combined hetEM/IM and PM patients.

^bHazard ratios are unadjusted and population heterogeneity was accounted for.

^cHazard ratios from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) 100-month analysis²⁹ shown as reciprocals: 1/0.76 for time to recurrence and 1/0.85 for event-/disease-free survival.

^dP Values of 1-sided, 1-sample Mantel-Haenszel log-rank tests, testing the alternative hypotheses that the hazard ratio of hetEM/IM, PM, or decreased vs EM group exceeds the hazard ratio of tamoxifen vs aromatase inhibitor group in the ATAC 100-month analysis.²⁹

^eEvent-free survival in this study corresponds to disease-free survival in the ATAC definition.