Trial Outcomes & Findings for Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer (NCT NCT00873366)

Last Updated: 2018-01-23

Results Overview

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The distribution of CYP2D6 genotypes grouped by CYP2D6 metabolism phenotype for each participants are summarized below.

Recruitment status

TERMINATED

Target enrollment

92 participants

Primary outcome timeframe

Baseline

Results posted on

2018-01-23

Participant Flow

Ninety one women and one man were enrolled between May 2009 and September 2011.

Six women withdrew consent prior to the start of testing. Another 9 participants were excluded from the analysis cohort due to: non-adherence to tamoxifen (N=2), use of a CYP2D6 inhibitor (N=1) and lack of sufficient samples for ¹³Cdextromethorphan analysis (N=6).

Participant milestones

Participant milestones
Measure	¹³C-DM-BT Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Overall Study STARTED	77
Overall Study COMPLETED	71
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	¹³C-DM-BT Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Overall Study Off tamoxifen for reconstructive surgery	1
Overall Study Off tamoxifen due to side effects	2
Overall Study Refused to continue DM-BT testing	3

Baseline Characteristics

Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	¹³C-DM-BT n=77 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Age, Continuous	52 years n=93 Participants
Sex/Gender, Customized Female	77 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	74 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	77 Participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0=Asymptomatic and fully active	73 Participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1=Symptomatic and fully ambulatory	4 Participants n=93 Participants
Body Mass Index (BMI)	26.8 kg/m^2 n=93 Participants
Disease Status Noninvasive Breast Cancer (DCIS)	4 Participants n=93 Participants
Disease Status Invasive Breast Cancer in Adjuvant	72 Participants n=93 Participants
Disease Status Invasive Breast Cancer in Metastatic	1 Participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=77 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers IM/PM (4/9)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers IM/PM (4/10)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers IM/PM (4/41)	4 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers PM/PM (3/4)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers PM/PM (4/4)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/EM (1/1)	12 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/EM (1/2A)	13 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/EM (1/2)	2 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/EM (2/2)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/EM (2A/2A)	2 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/IM (1/9)	2 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/IM (1/10)	3 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/IM (1/41)	7 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/IM (2A/9)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/IM (2A/41)	2 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (1/3)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (1/4)	8 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (2/4)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (2/4XN)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (2A/4)	6 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (2A/5)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/PM (2A/6)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/UM (1/2AXN)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers IM/IM (41/41)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers IM/PM (3/41)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers EM/UM (1/1XN)	1 Participants
Operating Characteristics of the ¹³C-dextromethorphan (13C-DM) Breath Test in Identifying Those Who Are CYP2D6 Genotypic Poor Metabolizers IM/UM (41/2AXN)	1 Participants

SECONDARY outcome

Timeframe: Baseline, 3 month and 6 month

Population: All eligible participants with DM-BT values.

Spearman rank order correlation coefficients were used to assess the strength of the association between CYP2D6 genotype activity score and DM-BT values.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=77 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between CYP2D6 Genotype and ¹³Cdextromethorphan Breath Test (DM-BT) Baseline	0.55 Correlation coefficient
Spearman's Rank Correlation Coefficient Between CYP2D6 Genotype and ¹³Cdextromethorphan Breath Test (DM-BT) 3 Month	0.58 Correlation coefficient
Spearman's Rank Correlation Coefficient Between CYP2D6 Genotype and ¹³Cdextromethorphan Breath Test (DM-BT) 6 Month	0.55 Correlation coefficient

SECONDARY outcome

Timeframe: 3 Month and 6 Month

Population: All eligible participants with Endoxifen pharmacokinetics data.

Spearman rank order correlation coefficients were used to assess the strength of the association between CYP2D6 genotype activity score and Endx Css

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between CYP2D6 Activity Score and Endoxifen Steady State Concentrations (Endx Css) 3 Month	0.47 Correlation coefficient
Spearman's Rank Correlation Coefficient Between CYP2D6 Activity Score and Endoxifen Steady State Concentrations (Endx Css) 6 Month	0.56 Correlation coefficient

SECONDARY outcome

Timeframe: 3 Month and 6 Month

Population: All eligible participants with Endoxifen pharmacokinetics data.

Spearman rank order correlation coefficients were used to assess the strength of the association between CYP2D6 genotype activity score and Endx/NDMT ratio

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between CYP2D6 Activity Score and Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio 3 Month	0.60 Correlation coefficient
Spearman's Rank Correlation Coefficient Between CYP2D6 Activity Score and Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio 6 Month	0.61 Correlation coefficient

SECONDARY outcome

Timeframe: Baseline, 3 month

Population: All eligible participants with DM-BT values and Endoxifen pharmacokinetics data.

Spearman rank order correlation coefficients were used to assess the strength of the association between baseline ¹³Cdextromethorphan breath test (DM-BT) and Endoxifen steady state concentrations (Endx Css)

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between Baseline DM-BT and 3 Month Endoxifen Steady State Concentrations	0.6 Correlation coefficient

SECONDARY outcome

Timeframe: Baseline, 3 month

Population: All eligible participants with DM-BT values and Endoxifen pharmacokinetics data.

Spearman rank order correlation coefficients were used to assess the strength of the association between baseline ¹³Cdextromethorphan breath test (DM-BT) and Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between Baseline DM-BT and 3 Month Endoxifen/N-desmethyl-tamoxifen (Endx/NDMT) Ratio	0.56 Correlation coefficient

SECONDARY outcome

Timeframe: 3 month

Population: All eligible participants with DM-BT values and Endoxifen pharmacokinetics data.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=56 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between 3 Month DM-BT and 3 Month Endoxifen Steady State Concentrations	0.51 Correlation coefficient

SECONDARY outcome

Timeframe: 6 month

Population: All eligible participants with DM-BT values and Endoxifen pharmacokinetics data.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=53 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Spearman's Rank Correlation Coefficient Between 6 Month DM-BT and 6 Month Endoxifen Steady State Concentrations	0.54 Correlation coefficient

SECONDARY outcome

Timeframe: 3 Month

Population: All eligible participants with pharmacokinetic data available. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 3 month Tamoxifen steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/PM	219.6 nM Interval 111.3 to 327.9
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/PM	233.8 nM Interval 114.8 to 275.0
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/IM	272.3 nM Only one participant has the data.
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/EM	257.7 nM Interval 163.0 to 514.1
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/IM	279.1 nM Interval 135.8 to 416.5
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/EM	201.0 nM Interval 134.7 to 401.4
Median of 3 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/UM	313.3 nM Only one participant has the data.

SECONDARY outcome

Timeframe: 6 Month

Population: All eligible participants with pharmacokinetic data available. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 6 month Tamoxifen steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=54 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/PM	194.0 nM Interval 149.3 to 238.7
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/PM	200.5 nM Interval 117.3 to 295.6
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/IM	279.2 nM There is only one participant with the data.
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/EM	259.7 nM Interval 47.2 to 436.6
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/IM	234.7 nM Interval 128.7 to 318.6
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/EM	179.7 nM Interval 96.6 to 460.5
Median of 6 Month Tamoxifen Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/UM	301.4 nM Interval 260.7 to 342.1

SECONDARY outcome

Timeframe: 3 Month

Population: All eligible participants with pharmacokinetic data available. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 3 month NDMT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/PM	633.3 nM Interval 429.0 to 837.7
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/PM	578.0 nM Interval 387.6 to 786.2
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/IM	691.6 nM There is only one participant with the data.
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/EM	643.0 nM Interval 514.6 to 885.1
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/IM	630.7 nM Interval 362.5 to 899.8
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/EM	457.8 nM Interval 325.4 to 766.7
Median of 3 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/UM	576.9 nM There is only one participant with the data.

SECONDARY outcome

Timeframe: 6 Month

Population: All eligible participants with Endoxifen pharmacokinetics data. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 6 month NDMT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=54 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/PM	554.6 nM Interval 438.5 to 670.7
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/PM	542.4 nM Interval 296.2 to 813.6
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/IM	718.2 nM There is only one participant with the data.
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/EM	546.5 nM Interval 232.7 to 979.5
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/IM	525.9 nM Interval 373.2 to 913.8
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/EM	401.8 nM Interval 280.9 to 867.7
Median of 6 Month N-desmethyl-tamoxifen (NDMT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/UM	552.9 nM Interval 481.2 to 624.5

SECONDARY outcome

Timeframe: 3 Month

Population: All eligible participants with pharmacokinetics data. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 3 month 4HT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/PM	3.13 nM Interval 2.79 to 3.47
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/PM	1.5 nM Interval 1.1 to 3.45
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/IM	3.52 nM There is only one participant with the data.
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/EM	3.62 nM Interval 2.08 to 8.77
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/IM	5.41 nM Interval 2.75 to 16.82
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/EM	3.64 nM Interval 1.38 to 20.05
Median of 3 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/UM	4.21 nM There is only one participant with the data.

SECONDARY outcome

Timeframe: 6 Month

Population: All eligible participants with pharmacokinetic data available. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 6 month 4HT steady state plasma concentrations for each CYP2D6 phenotype group are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=54 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/PM	3.17 nM Interval 2.15 to 4.19
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/PM	1.69 nM Interval 1.37 to 3.02
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group IM/IM	1.5 nM There is only one participant with the data.
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group PM/EM	3.81 nM Interval 1.37 to 12.07
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/IM	5.86 nM Interval 2.48 to 14.1
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/EM	2.96 nM Interval 1.18 to 14.1
Median of 6 Month 4-hydroxy-tamoxifen (4HT) Steady State Plasma Concentrations According to CYP2D6 Phenotype Group EM/UM	5.38 nM Interval 5.24 to 5.51

SECONDARY outcome

Timeframe: 3 Month

Population: All eligible participants with Endoxifen pharmacokinetics data. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 3 month Endx Css for each CYP2D6 phenotype group and the corresponding activity score are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=57 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/UM (3.0)	23.6 nM There is only one participant with the data.
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/EM (2.0)	30.5 nM Interval 9.1 to 74.3
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/IM (1.5)	27.9 nM Interval 17.0 to 44.7
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score IM/IM (1.0)	11.5 nM There is only one participant with the data.
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/PM (1.0)	21.5 nM Interval 8.6 to 50.9
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score IM/PM (0.5)	6.1 nM Interval 4.3 to 8.5
Median of 3 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score PM/PM (0)	5.5 nM Interval 4.6 to 6.4

SECONDARY outcome

Timeframe: 6 Month

Population: All eligible participants with Endoxifen pharmacokinetics data. Data was not collected for the one participant with CYP2D6 phenotype group as IM/UM.

Participants were classified as having CYP2D6 decreased or non-decreased metabolism based on genotype and the co-prescription of inhibitors of the enzyme system. The specific phenotype, alleles and their associated activity score (AS) assessed were as follows: Ultrarapid metabolism (UM) or AS=2.0 (\*1XN or \*2XN), Extensive metabolism (EM) or AS=1.0 (\*1, \*2, and \*2A), Intermediate metabolism (IM) or AS=0.5 (\*9, \*10, \*17 and \*41), and Poor metabolism (PM) or AS=0.0 (3, \*4, \*5, \*7, \*8, \*11, and \*12). The median of 6 month Endx Css for each CYP2D6 phenotype group and the corresponding activity score are summarized below. Refer to Outcome Measure 1 Data Table for details on the combination of genotype for each participant that are defined for each CYP2D6 phenotype group.

Outcome measures

Outcome measures
Measure	¹³C-DM-BT n=54 Participants Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/UM (3.0)	38.5 nM Interval 23.1 to 53.9
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/EM (2.0)	26.7 nM Interval 10.9 to 72.9
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/IM (1.5)	30.4 nM Interval 16.1 to 38.3
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score IM/IM (1.0)	11.3 nM There is only one participant with the data.
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score EM/PM (1.0)	19.1 nM Interval 4.8 to 53.2
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score IM/PM (0.5)	4.7 nM Interval 2.9 to 12.0
Median of 6 Month Endoxifen Steady State Concentrations (Endx Css) According to CYP2D6 Phenotype Group and Activity Score PM/PM (0)	6.7 nM Interval 6.4 to 7.1

Adverse Events

¹³C-DM-BT

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	¹³C-DM-BT n=70 participants at risk Participants who have provided blood samples and underwent a ¹³Cdextromethorphan breath test (¹³C-DM-BT) on day 1, once during week 8-10 following initiation of tamoxifen, and once during either month 5-6 post tamoxifen initiation.
Nervous system disorders Dizziness	2.9% 2/70 • Number of events 3 • 6 month All eligible participants with adverse events data reported. Adverse events data were not available on 7 participants.

Additional Information

Dr. Matthew P. Goetz

Mayo Clinic

Phone: 507-284-2511

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place