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©The Author(s) 2022.
World J Clin Oncol. Aug 24, 2022; 13(8): 712-724
Published online Aug 24, 2022. doi: 10.5306/wjco.v13.i8.712
Published online Aug 24, 2022. doi: 10.5306/wjco.v13.i8.712
Table 1 Primers for cytochrome P450 2D6 genotyping
Position/change | Forward primer (5’→3’) | Reverse primer (5’→3’) | |
*4 | 1846G>A | AGA GGC GCT TCT CCG TGT CC | AAA TCC TGC TCT TCC GAG GC |
*5 | Gene deletion | CTC CAG CCT CCA CCA GTC CAG | CAG GCA TGA GCT AAG GCA CCC AGA C |
*6 | 1707delT | CGC AAC TTG GGC CTG GGC AAG AAG TCG CTG GAC TAG | CTC GGG AGC TCG CCC TGC AGA GAC TC |
*9 | 2613AGA>del | GGT CAG TGG TAA GGA CAG GCA GGC CC | CAC CCT TGC CCC CCA CCG TGG CAG CCA CTC TAA GCT |
*10 | 100C>T | GAT GCA CCG GCG CCA ACG CTG GGC TGC ACG GTA C | CAA ACC TGC TTC CCC TTC TCA GCC |
*41 | 2988G>A | CGT GAG CCC ATC TGG GAA A | CTG ACA CTC CTT CTT GCC TCC TA |
Table 2 Details of cytochrome P450 2D6 genotyping for the 78 women classified into two phenotype groups: Intermediate metabolizers and extensive metabolizers/ultra metabolizers
Phenotype | CYP2D6 genotype | Number of women, n = 78 |
IM | *10/*10 | 25 |
*10/41 | 2 | |
*10/*4 | 2 | |
*10/*5 | 3 | |
*10/EM/UM | 20 | |
*5/EM/UM | 5 | |
EM/UM | EM/UM | 21 |
Table 3 Univariate correlation analyses of clinicopathological parameters with cytochrome P450 2D6 phenotype classification
IM phenotype, n = 52 | EM/UM phenotype, n = 18 | P value | |
Median age in yr | 62.5 (51-86) | 61 (50-84) | 0.574 |
Disease stage | 0.595 | ||
I | 24 | 6 | |
II | 17 | 8 | |
III | 11 | 4 | |
Ethnicity | 0.148 | ||
Chinese | 47 | 13 | |
Malay | 3 | 3 | |
Indian | 1 | 2 | |
Others | 1 | 0 | |
Comorbidities | 0.728 | ||
Yes | 43 | 14 | |
No | 9 | 4 | |
Tumor histology | 0.518 | ||
IDC | 40 | 14 | |
ILC | 7 | 1 | |
Others | 5 | 3 | |
Tumor grade | 0.247 | ||
1 | 16 | 3 | |
2 | 25 | 10 | |
3 | 11 | 5 | |
Median tumor size in mm | 16.5 (1.2 to 70.0) | 20.0 (3.0 to 45.0) | 0.334 |
Lymphovascular invasion | 0.527 | ||
Present | 16 | 7 | |
Absent | 36 | 11 | |
ER intensity | 0.528 | ||
Low | 2 | 0 | |
Moderate | 11 | 2 | |
High | 38 | 15 | |
Negative | 1 | 1 | |
Proportion of tumor cells staining ER-positive | 0.267 | ||
1% to 10% | 4 | 0 | |
11% to 49% | 6 | 1 | |
50% to 89% | 14 | 3 | |
More than 90% | 27 | 14 | |
PR intensity | 0.631 | ||
Low | 5 | 1 | |
Moderate | 9 | 5 | |
High | 31 | 11 | |
Negative | 7 | 1 | |
Proportion of tumor cells staining PR-positive | 0.785 | ||
1% to 10% | 11 | 3 | |
11% to 49% | 8 | 2 | |
50% to 89% | 18 | 7 | |
More than 90% | 11 | 6 | |
HER2 status | 0.495 | ||
Positive | 11 | 2 | |
Negative | 41 | 16 | |
Clinical subtypes | 0.692 | ||
ER+/HER2- | 41 | 14 | |
ER+/HER2+ | 10 | 2 | |
ER-/HER2+ | 1 | 0 |
Table 4 Univariate correlation analyses of clinicopathological parameters and clinical outcome with type of hormonal agent received
Aromatase inhibitors, n = 56 | Tamoxifen, n = 14 | P value | |
CYP2D6 phenotype | 0.339 | ||
IM | 43 | 9 | |
EM/UM | 13 | 5 | |
Median age in yr | 62 (50 to 80) | 63 (52 to 86) | 0.008 |
Disease stage | 0.795 | ||
I | 23 | 7 | |
II | 21 | 4 | |
III | 12 | 3 | |
Ethnicity | 0.126 | ||
Chinese | 50 | 10 | |
Malay | 3 | 2 | |
Indian | 3 | 1 | |
Others | 0 | 1 | |
Comorbidities | 1.000 | ||
Yes | 45 | 12 | |
No | 11 | 2 | |
Tumor histology | 0.918 | ||
IDC | 45 | 11 | |
ILC | 6 | 2 | |
Others | 5 | 1 | |
Tumor grade | 0.686 | ||
1 | 15 | 4 | |
2 | 27 | 8 | |
3 | 14 | 2 | |
Median tumor size in mm | 16.5 (1.2 to 70.0) | 19.0 (1.6 to 53.0) | 0.747 |
Lymphovascular invasion | 0.526 | ||
Yes | 17 | 6 | |
No | 39 | 8 | |
ER intensity | 0.509 | ||
Low intensity | 1 | 1 | |
Moderate intensity | 10 | 4 | |
High intensity | 44 | 9 | |
Negative | 1 | 0 | |
Proportion of tumor cells staining ER-positive | 0.386 | ||
1%-10% | 3 | 1 | |
11% to 49% | 4 | 3 | |
50% to 89% | 15 | 2 | |
More than 90% | 33 | 8 | |
PR status | 1.000 | ||
Positive | 49 | 13 | |
Negative | 7 | 1 | |
PR intensity | 0.161 | ||
Low intensity | 3 | 3 | |
Moderate intensity | 10 | 4 | |
High intensity | 36 | 6 | |
Negative | 7 | 1 | |
Proportion of tumor cells staining PR-positive | 0.318 | ||
1%-10% | 11 | 3 | |
11% to 49% | 6 | 4 | |
50% to 89% | 21 | 4 | |
More than 90% | 15 | 2 | |
HER2 status | 0.700 | ||
Positive | 10 | 3 | |
Negative | 46 | 10 | |
Tumor subtypes | 0.754 | ||
ER+/HER2- | 46 | 10 | |
ER+/HER2+ | 9 | 3 | |
ER-/HER2+ | 1 | 0 | |
Type of surgery | 0.756 | ||
Mastectomy | 35 | 10 | |
Wide local excision | 21 | 4 | |
Treatments received | 0.045 | ||
Systemic therapy1 and hormonal therapy | 12 | 2 | |
Systemic therapy1, radiation and hormonal therapy | 18 | 0 | |
Radiation and hormonal therapy | 12 | 5 | |
Hormonal therapy alone | 14 | 7 | |
Disease recurrence2 | 0.260 | ||
Yes | 3 | 2 | |
No | 53 | 12 | |
Mortality2 | 0.344 | ||
Yes | 1 | 1 | |
No | 55 | 13 | |
Contralateral breast cancer2 | 0.551 | ||
Yes | 2 | 1 | |
No | 54 | 13 |
- Citation: Tan EY, Bharwani L, Chia YH, Soong RCT, Lee SSY, Chen JJC, Chan PMY. Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer. World J Clin Oncol 2022; 13(8): 712-724
- URL: https://www.wjgnet.com/2218-4333/full/v13/i8/712.htm
- DOI: https://dx.doi.org/10.5306/wjco.v13.i8.712