A                Distant recurrence  - tamoxifen
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A Distant recurrence - tamoxifen. *4/WT. 20%. WT/WT. 15%. * 4/* 4. Recurrence (%). 10%. 5%. 0%. 0. 2. 4. 6. 8. 10. Follow-up time [years]. No. of patients at risk. WT/WT. 402. 379. 353. 317. 249. 5. *4/WT. 149. 137. 131. 120. 95. 0. *4/*4. 37. 35.

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A Distant recurrence - tamoxifen

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A distant recurrence tamoxifen

A Distant recurrence - tamoxifen

*4/WT

20%

WT/WT

15%

*4/*4

Recurrence (%)

10%

5%

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

WT/WT

402

379

353

317

249

5

*4/WT

149

137

131

120

95

0

*4/*4

37

35

33

30

24

1


A distant recurrence tamoxifen

B Any recurrence - tamoxifen

*4/WT

30%

WT/WT

20%

Recurrence (%)

*4/*4

10%

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

WT/WT

402

376

347

307

238

4

*4/WT

149

135

127

114

90

0

*4/*4

37

35

33

29

21

0


A distant recurrence tamoxifen

Supplementary Figure 1. Probability of recurrence in patients enrolled in the ATAC trial according to CYP2D6*4 genotype. Recurrence was assessed in patients who were randomly assigned to the tamoxifen group using a Cox proportional hazard model. Homozygous wild-type CYP2D6, ie,CYP2D6*1/*1, is shown as WT/WT,heterozygous CYP2D6*4, ie, CYP2D6*4/WT is shown as *4/WT, and homozygous CYP2D6*4, ie, CYP2D6*4/*4 is shown as *4/*4. Two-sided P values were calculated using an adjusted Cox proportional hazard model. A) Distant recurrence. B) Any recurrence. HR = hazard ratio; CI = confidence interval.


A distant recurrence tamoxifen

A Distant recurrence - tamoxifen

*2/*2

20%

*2/WT

15%

WT/WT

Recurrence (%)

10%

5%

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

121

114

109

96

73

0

WT/WT

*2/WT

274

257

238

218

177

3

*2/*2

174

162

153

136

102

3


A distant recurrence tamoxifen

B Any recurrence - tamoxifen

*2/WT

*2/*2

20%

Recurrence (%)

10%

WT/WT

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

WT/WT

121

114

108

94

72

0

*2/WT

274

255

231

206

163

1

*2/*2

174

159

151

133

98

3


A distant recurrence tamoxifen

Supplementary Figure 2. Probability of recurrence in patients enrolled in the ATAC trial according to UGT2B7*2genotype. Recurrence was assessed in patients who were randomly assigned to the tamoxifen group using a Cox proportional hazard model. Homozygous wild-type UGT2B7, ie, UGT2B7*1/*1 is shown as WT/WT, heterozygous UGT2B7*2, ie, UGT2B7*2/WT is shown as *2/WT, and homozygous UGT2B7*2, ie, UGT2B7*2/*2 is shown as *2/*2. Two-sided P values were calculated using an adjusted Cox proportional hazard model. A) Distant recurrence. B) Any recurrence. HR = hazard ratio; CI = confidence interval.


A distant recurrence tamoxifen

A Distant recurrence - anastrozole

EM (2)

20%

15%

IM (1)

10%

IM (0.5)

Recurrence (%)

PM (0)

5%

IM (1.5)

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

PM (0)

41

41

39

35

27

0

IM (0.5)

21

20

19

17

16

0

IM (1)

146

138

130

117

98

5

IM (1.5)

45

44

43

41

32

0

EM (2)

362

346

328

302

242

2


A distant recurrence tamoxifen

B Any recurrence - anastrozole

EM (2)

IM (0.5)

20%

IM (1)

Recurrence (%)

IM (1.5)

10%

PM (0)

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

PM (0)

41

40

38

34

26

0

IM (0.5)

21

20

19

16

15

0

IM (1)

146

138

130

116

97

5

IM (1.5)

45

44

43

41

31

0

EM (2)

362

345

323

297

234

2


A distant recurrence tamoxifen

Supplementary Figure 3. Probability of recurrence in patients enrolled in the ATAC trial according to CYP2D6 phenotype. Recurrence was assessed in patients who were randomly assigned to the anastrozole group using a Cox proportional hazard model. A CYP2D6 activity score was assigned to each patient, which most accurately predict a patient’s CYP2D6 metabolic phenotype based on their genotype (31). The phenotypic scores are indicated in parentheses. Two-sided P values were calculated using an adjusted Cox proportional hazard model. A) Distant recurrence. B) Any recurrence. HR = hazard ratio; CI = confidence interval; PM = poor metabolizer, IM = intermediate metabolizer, EM = extensive metabolizer.


A distant recurrence tamoxifen

A Distant recurrence - anastrozole

WT/WT

20%

15%

*2/*2

Recurrence (%)

10%

*2/WT

5%

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

WT/WT

121

116

110

97

71

2

*2/WT

293

280

265

245

210

4

*2/*2

173

167

159

147

113

1


A distant recurrence tamoxifen

B Any recurrence - anastrozole

WT/WT

20%

15%

*2/WT

10%

Recurrence (%)

5%

*2/*2

0%

0

2

4

6

8

10

Follow-up time [years]

  • No. of patients at risk

WT/WT

121

116

110

97

70

2

*2/WT

293

278

261

240

203

4

*2/*2

173

167

157

144

110

1


A distant recurrence tamoxifen

Supplementary Figure 4. Probability of recurrence in patients enrolled in the ATAC trial according to UGT2B7*2 genotype. Recurrence was assessed in patients who were randomly assigned to the anastrozole group using a Cox proportional hazard model. Homozygous wild-type UGT2B7, ie, UGT2B7*1/*1 is shown as WT/WT, heterozygous UGT2B7*2, ie, UGT2B7*2/WT is shown as *2/WT, and homozygous UGT2B7*2, ie, UGT2B7*2/*2 is shown as *2/*2. Two-sided P values were calculated using an adjusted Cox proportional hazard model. A) Distant recurrence. B) Any recurrence. HR = hazard ratio; CI = confidence interval.


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