Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer

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

IM: Intermediate metabolizers; EM/UM: Extensive metabolizers/ultra metabolizers; CYP2D6: Cytochrome P450 2D6.

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

ER: Estrogen receptor; PR: Progesterone receptor; HER2: Human epidermal growth factor receptor-2; IDC: Invasive ductal carcinoma; ILC: Invasive lobular carcinoma; IM: Intermediate metabolizers; EM/UM: Extensive metabolizers/ultra metabolizers.

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

¹Systemic therapy refers to chemotherapy with or without trastuzumab.

²Events occurring within 5 years.

ER: Estrogen receptor; PR: Progesterone receptor; HER2: Human epidermal growth factor receptor-2; IDC: Invasive ductal carcinoma; ILC: Invasive lobular carcinoma; IM: Intermediate metabolizers; EM/UM: Extensive metabolizers/ultra metabolizers; CYP2D6: Cytochrome P450 2D6.