Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience

Table 1 Clinical and histopathological characteristics of human epidermal growth factor receptor 2 positive and human epidermal growth factor receptor 2 negative invasive lobular carcinomas patients, n (%)

Characteristics	HER2+ (n = 87)		HER2- (n = 777)		Total (n = 864)		P value
Age (yr)							1.000
≤ 50	30 (34.5)		272 (35.0)		302 (35.0)
> 50	57 (65.5)		505 (65.0)		562 (65.0)
Ethnicity							0.594
Chinese	68 (78.2)		558 (72.1)		626 (72.7)
Indian	4 (4.6)		60 (7.8)		64 (7.4)
Malay	8 (9.2)		68 (8.8)		76 (8.8)
Others	7 (8.0)		88 (11.4)		95 (11.0)
ER							< 0.001
Negative	21 (24.4)		46 (5.9)		67 (7.8)
Positive	65 (75.6)		730 (94.1)		795 (7.8)
PR							0.002
Negative	35 (40.2)		185 (24.0)		220 (25.6)
Positive	52 (59.8)		587 (76.0)		639 (74.4)
Tumour size							0.765
0.1-2 cm	21 (41.2)		230 (38.7)		251 (38.9)
> 2 cm	30 (58.8)		365 (61.3)		395 (61.1)
Tumour grade							<0.001
Grade 1	7 (10.1)		148 (22.5)		155 (21.3)
Grade 2	42 (60.9)		443 (67.3)		485 (66.7)
Grade 3	20 (29.0)		67 (10.2)		87 (12.0)
Tumour stage							0.066
Stage 1	20 (24.1)		216 (30.3)		236 (29.7)
Stage 2	25 (30.1)		267 (37.5)		292 (36.7)
Stage 3	27 (32.5)		179 (25.1)		206 (25.9)
Stage 4	11 (13.3)		50 (7.0)		61 (7.7)
Treatment
Chemotherapy1	50 (66.7)		390 (54.2)		440 (55.3)		0.038
With HER2 therapy	47 (54.0)		-	-	47 (54.0)
No HER2 therapy	12 (13.8)		-	-	12 (13.8)
Unknown if any HER2 therapy	28 (32.2)		-	-	28 (32.2)
Radiotherapy2	47 (62.7)		404 (56.1)		451 (56.7)		0.276
Surgery3	73 (92.4)		690 (92.1)		763 (92.1)		0.929

¹There were 69 patients with unknown chemotherapy histories which were excluded from analysis.

²There were 69 patients with unknown radiotherapy histories which were excluded from analysis.

³There were 36 patients with unknown surgery histories which were excluded from analysis. HER2: Human epidermal growth factor receptor 2; HER2+: Human epidermal growth factor receptor 2 positive; HER2-: Human epidermal growth factor receptor 2 negative; ER: Estrogen receptor; PR: Progesterone receptor.

Table 2 Univariate and multivariate Cox proportional hazard regression analysis for overall survival among all 864 invasive lobular carcinomas patients

Characteristics	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age (reference: ≤ 50 yr)
> 50 yr	2.32	1.68-3.20	< 0.001	2.17	1.37-3.44	< 0.001
Ethnicity (reference: Chinese)			< 0.0011			0.0011
Indian	2.53	1.62-3.94	< 0.001	3.41	1.78-6.54	< 0.001
Malay	0.95	0.50-1.82	0.889	0.98	0.42-2.29	0.961
Others	0.40	0.15-1.08	0.070	0.64	0.19-2.12	0.462
ER (reference: Negative)
Positive	0.74	0.44-1.24	0.255
PR (reference: Negative)
Positive	0.62	0.44-0.87	0.005	0.57	0.35-0.91	0.018
HER2 (reference: Negative)
Positive	1.87	1.21-2.90	0.005	2.14	1.16-3.95	0.016
Tumour size (reference: ≤ 2 cm)
> 2 cm	2.43	1.45-4.06	< 0.001
Tumour stage (reference: Stage 1)			< 0.0011			< 0.0011
Stage 2	2.33	1.09-4.99	0.030	1.75	0.76-4.03	0.191
Stage 3	6.98	3.42-14.25	< 0.001	4.52	2.06-9.89	< 0.001
Stage 4	61.82	29.73-128.57	< 0.001	41.74	17.95-97.04	< 0.001
Tumor grade (reference: Grade 1)			< 0.0011			0.0751
Grade 2	1.45	0.83-1.89	0.190	1.05	0.57-1.93	0.877
Grade 3	4.72	2.55-8.74	< 0.001	1.89	0.93-3.84	0.079
Chemotherapy (reference: No)
Yes	0.97	0.69-1.37	0.866
Surgery (reference: No)
Yes	0.06	0.04-0.09	< 0.001
Radiotherapy (reference: No)
Yes	0.89	0.63-1.27	0.518
Molecular subtype (reference: Luminal A)			0.0251			0.0021
Basal	1.52	0.79-2.90	0.206	1.13	0.38-3.29	0.830
HER2 positive	2.08	0.85-5.10	0.108	4.21	1.43-12.44	0.009
Luminal B	1.89	1.16-3.07	0.011	2.52	1.41-4.49	0.002

¹Refers to type 3 P value. HR: Hazard ratio; CI: Confidence interval; HER2: Human epidermal growth factor receptor 2; ER: Estrogen receptor; PR: Progesterone receptor.

Table 3 Univariate and multivariate Cox proportional hazard regression analysis for breast cancer-specific survival among all 864 invasive lobular carcinomas patients

Characteristics	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI		P value
Age (reference: ≤ 50 yr)
> 50 yr	2.16	1.53-3.05	< 0.001
Ethnicity (reference: Chinese)			< 0.0011				0.0041
Indian	2.60	1.63-4.14	< 0.001	2.55	1.28-5.05		0.008
Malay	0.89	0.43-1.82	0.744	1.07	0.43-2.67		0.885
Others	0.32	0.10-1.02	0.054	0.19	0.04-0.84		0.028
ER (reference: Negative)
Positive	0.72	0.42-1.26	0.255
PR (reference: Negative)
Positive	0.61	0.42-0.88	0.008	0.40	0.23-0.70		0.001
HER2 (reference: Negative)
Positive	2.08	1.32-3.26	0.002
Molecular subtype (reference: Luminal A)			0.0111				0.0041
Basal	1.49	0.72-3.07	0.281	1.16	0.36-3.77		0.801
HER2+	2.34	0.95-5.74	0.064	3.74	1.26-11.09		0.018
Luminal B	2.08	1.26-3.44	0.004	2.79	1.44-5.37		0.002
Tumour size (reference: ≤ 2 cm)
> 2 cm	2.76	1.53-4.97	< 0.001
Tumour stage (reference: Stage 1)			< 0.0011				< 0.001
Stage 2	3.11	1.09-8.92	0.034	2.19	0.74-6.49		0.159
Stage 3	13.02	4.89-34.68	< 0.001	6.49	2.35-17.89		< 0.001
Stage 4	117.79	43.5-317.87	< 0.001	56.27	18.44-171.68		< 0.001
Tumor grade (reference: Grade 1)			< 0.0011				0.0011
Grade 2	1.89	0.96-3.75	0.066	1.63	0.78-3.44		0.196
Grade 3	7.10	3.44-14.64	< 0.001	4.16	1.80-9.62		0.001
Chemotherapy (reference: No)
Yes	1.23	0.84-1.80	0.290
Surgery (reference: No)
Yes	0.06	0.04-0.08	< 0.001	0.23	0.11-0.51		< 0.001
Radiotherapy (reference: No)
Yes	0.94	0.65-1.37	0.758

¹Refers to type 3 P value. HR: Hazard ratio; CI: Confidence interval; HER2: Human epidermal growth factor receptor 2; ER: Estrogen receptor; PR: Progesterone receptor; HER2+: Human epidermal growth factor receptor 2 positive.

Table 4 Univariate and multivariate Cox proportional hazard regression analysis for disease-free survival among all 864 invasive lobular carcinomas patients

Characteristics	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Age (reference: ≤ 50 yr)
> 50 yr	1.60	1.11-2.30	0.012	1.63	1.04-2.55	0.033
Ethnicity (reference: Chinese)			0.001
Indian	2.61	1.52-4.48	< 0.001
Malay	0.99	0.48-2.05	0.984
Others	1.99	1.10-3.58	0.022
ER (reference: Negative)
Positive	1.04	0.57-1.90	0.886
PR (reference: Negative)
Positive	0.97	0.65-1.43	0.876
HER2 (reference: Negative)
Positive	1.68	1.04-2.71	0.03
Molecular subtype (reference: Luminal A)			0.2171
Basal	0.98	0.45-2.12	0.965
HER2+	1.69	0.62-4.61	0.304
Luminal B	1.67	0.98-2.83	0.058
Tumour size (reference: ≤ 2 cm)
> 2 cm	2.02	1.26-3.25	0.004
Tumour stage (reference: Stage 1)			< 0.0011			< 0.0011
Stage 2	1.92	1.05-3.53	0.035	1.66	0.83-3.28	0.149
Stage 3	5.66	3.21-9.98	< 0.001	5.26	2.76-10.03	< 0.001
Stage 4	0.62	0.04-10.84	0.745	0.71	0.04-12.61	0.813
Tumor grade (reference: Grade 1)			< 0.0011			0.0131
Grade 2	1.79	1.02-3.16	0.044	1.32	0.73-2.40	0.357
Grade 3	3.72	1.89-7.34	< 0.001	2.69	1.32-5.50	0.007
Chemotherapy (reference: No)
Yes	1.64	1.12-2.42	0.011
Surgery (reference: No)
Yes	0.14	0.08-0.23	< 0.001
Radiotherapy (reference: No)
Yes	1.57	1.05-2.34	0.028

¹Refers to type 3 P value. HR: Hazard ratio; CI: Confidence interval; HER2: Human epidermal growth factor receptor 2; ER: Estrogen receptor; PR: Progesterone receptor; HER2+: Human epidermal growth factor receptor 2 positive.