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Table 3 Association between tamoxifen treatment and risk of CBC stratified by CYP2D6 activity score in the WECARE Study populationa

From: CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study

Activity scoreb No tamoxifen treatment Tamoxifen treatment
Cases
N (%)
Controls
N (%)
RR
(95% CI)
Cases
N (%)
Controls
N (%)
RRc
(95% CI)
p d
2 395 (38) 549 (39) Reference 193 (42) 300 (38) 0.81 (0.62–1.06) 0.02
1.5 192 (18) 205 (14) Reference 65 (14) 141 (18) 0.45 (0.30–0.68)
1 317 (30) 436 (31) Reference 128 (28) 235 (30) 0.55 (0.40–0.74)
0.75 30 (3) 32 (2) Reference 20 (4) 23 (3) 0.64 (0.26–1.58)
0.5 58 (6) 98 (7) Reference 38 (8) 54 (7) 1.08 (0.59–1.96)
0 57 (5) 98 (7) Reference 21 (5) 32 (4) 1.17 (0.58–2.35)
Phenotypee
 EM 904 (86) 1190 (84) Reference 386 (83) 676 (86) 0.63 (0.51–0.78) 0.09
 IM 88 (8) 130 (9) Reference 58 (12) 77 (10) 0.95 (0.57–1.56)
 PM 57 (5) 98 (7) Reference 21 (5) 32 (4) 1.18 (0.59–2.37)
  1. CBC contralateral breast cancer, WECARE Women’s Environmental Cancer and Radiation Epidemiology, RR rate ratio, CI confidence interval, EM extensive metabolizer, IM intermediate metabolizer, PM poor metabolizer
  2. aAnalysis includes 1514 CBC cases and 2203 unilateral breast cancer controls
  3. bActivity score (AS) is derived from diploid phenotypes: PM/PM (AS = 0), PM/IM (AS = 0.5), IM/IM (AS = 0.75), PM/EM (AS = 1), IM/EM (AS = 1.5), and EM/EM (AS = 2)
  4. cAdjusted for: age at first primary, age at menopause 2 years prior to first primary cancer, histology of first primary cancer, stage of first primary cancer, family history of breast cancer, chemotherapy at first primary cancer, radiation at first primary cancer, other hormonal therapy at first primary cancer, number of full-term pregnancies at first primary cancer, age at menarche, estrogen receptor status of first breast cancer diagnosis, and an offset term to take into account the counter-matching for radiation treatment used in WECARE I
  5. dp value for the test that all RRs are equal across AS/phenotype categories (p for homogeneity)
  6. ePhenotype defined as: EM, having at least one EM allele (i.e., AS ≥ 1); IM, having no EM alleles and at least one IM allele (i.e., AS = 0.5–0.75); and PM, having two PM alleles (i.e., AS = 0)