Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients

Figures & data

Table 1 Correlation Between Baseline sHER2 Levels with Clinicopathological Characteristics in Patients with Advanced Breast Cancer

Clinicopathological Characteristics	Baseline sHER2 High Level	Baseline sHER2 Low Level	p	χ^2
	n (%)	n (%)
Total	132	68
tHER2			0.001	10.170
Negative	54 (40.90)	44 (64.71)
Positive	78 (59.10)	24 (35.29)
Age			0.327	2.236
≤35	12 (9.09)	8 (11.76)
35–65	113 (85.61)	53 (77.94)
≥65	7 (5.30)	7 (10.29)
Molecular subtype			0.016	12.229
Luminal A	2 (1.52)	4 (5.88)
Luminal B (tHER2 negative)	35 (26.52)	30 (44.12)
Luminal B (tHER2 positive)	33 (25.00)	10 (14.71)
tHER2 positive	45 (34.09)	14 (20.59)
TNBC	17 (12.88)	10 (14.71)
ER			0.060	3.540
Negative	63 (47.73)	23 (33.82)
Positive	69 (52.27)	45 (66.18)
PR			0.373	0.792
Negative	67 (50.76)	30 (44.12)
Positive	65 (49.24)	38 (55.88)
Visceral metastasis			<0.001	13.984
Yes	94 (71.21)	30 (44.12)
No	38 (28.79)	38 (55.88)
Liver metastasis			<0.001	19.052
Yes	53 (40.15)	7 (10.29)
No	79 (59.85)	61 (89.71)
Brain metastasis			0.579	0.308
Yes	15 (11.36)	6 (8.82)
No	117 (88.64)	62 (91.18)

Table 2 Correlation Between Baseline sHER2 Level and Therapeutic Efficacy

	Therapeutic Efficacy	Baseline sHER2 High Level (132)		Baseline sHER2 Low Level (68)		p	χ^2
tHER2 negative (98)	CR	0	54	0	44
	PR	14		8
	SD	35		31
	PD	5		5
	ORR	14 (25.93%) ^a		8 (18.18%) ^c		0.004 ^a	8.487 ^a
	DCR	49 (90.74%) ^b		39 (88.64%) ^d		0.543 ^b	0.370 ^b
tHER2 positive (102)	CR	0	78	1	24
	PR	40		8
	SD	33		15
	PD	5		0
	ORR	40 (51.28%) ^a		9 (37.50%) ^c		0.079 ^c	3.091^c
	DCR	73 (93.59%) ^b		24 (100%) ^d		0.086^d	2.944^d
Total	ORR	54 (40.91%) ^e	132	17 (25.00%) ^e	68	0.026^e	4.961^e
	DCR	122 (92.42%) ^f		66 97.06%) ^f		0.933^f	0.003^f

Notes: ORR = (CR + PR)/Total; DCR = (CR + PR + SD)/Total; ^aComparison of ORR between tHER2 positive and negative patients in the baseline sHER2 high level group. ^bComparison of DCR between tHER2 positive and negative patients in the baseline sHER2 high level group. ^cComparison of ORR between tHER2 positive and negative patients in the baseline sHER2 low level group. ^dComparison of DCR between tHER2 positive and negative patients in the baseline sHER2 low level group. ^eComparison of ORR between baseline sHER2 high level and baseline sHER2 low level patients. ^fComparison of DCR between baseline sHER2 high level and baseline sHER2 low level patients.

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progress disease; ORR, objective response rate; DCR, disease control rate.

Figure 1 Correlation of baseline sHER2 levels and prognosis (time to progression, TTP) in patients with advanced breast cancer. (A) Comparison of TTP between baseline sHER2 high level group and sHER2 low level group (p=0.048). Comparison of TTP between tHER2 positive patients and tHER2 negative patients in sHER2 high level group (B, p=0.142), and sHER2 low level group (C, p=0.059). Comparison of TTP between the sHER2 high level group and the sHER2 low level group in tHER2 positive patients (D, p=0.024) and negative patients (E, p=0.251).

Table 3 Correlation Between the Change of sHER2 Level and Therapeutic Efficacy in Baseline sHER2 High Level and Low Level Group After Two Treatment Cycles

	Therapeutic Efficacy	Significant Decrease (70)		No Significant Change (101)		Significant Increase (29)		p	χ^2
		Baseline sHER2 High Level (64)	Baseline sHER2 Low Level (6)	Baseline sHER2 High Level (58)	Baseline sHER2 low level (43)	Baseline sHER2 High Level (10)	Baseline sHER2 Low Level (19)
tHER2 negative (98)	CR	0	0	0	0	0	0
	PR	7	1	6	5	1	2
	SD	5	2	27	20	3	9
	PD	0	1	4	2	1	2
	ORR	8 (50.00%)		11 (17.19%)		3 (16.67%)		0.015	8.339
	DCR	15 (93.75%)		58 (90.63%)		15 (83.33%)		0.565	1141
	Total	16		64		18
tHER2 positive (102)	CR	0	0	0	1	0	0
	PR	32	1	7	5	1	2
	SD	19	1	10	10	4	4
	PD	1	0	4	0	0	0
	ORR	39 (60.94%)		13 (22.41%)		2 (20.00%)		<0.001	20.636
	DCR	63 (98.44%)		50 (86.21%)		9 (90.00%)		0.037	6.591
	ORR	33 (61.11%)		13 (35.14%)		3 (27.27%)		0.018	8.605
	DCR	53 (98.15%)		33 (89.19%)		33 (100%)		0.110	4.416
	Total	54		37		11
Total	ORR	41 (58.57%)		24 (23.76%)		6 (20.69%)		<0.001	25.128
	DCR	68 (97.14%)		91 (90.10%)		26 (89.66%)		0.187	3.353

Notes: ORR = (CR + PR)/Total; DCR = (CR + PR + SD)/Total.

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progress disease; ORR, objective response rate; DCR, disease control rate.

Figure 2 Correlation between the change of sHER2 level and prognosis (TTP) after two cycles of treatment. (A) Comparison of TTP between the significant decrease group, no significant change group, and significant increase group after two cycles of treatment. The comparison of TTP of three groups in the sHER2 high level group (B) and sHER2 low level group (C), respectively. The comparison of TTP of three groups in the tHER2 positive group (D) and tHER2 negative group (E), respectively.

Table 4 Correlation Between the Change of sHER2 Level and Therapeutic Efficacy in Baseline sHER2 High Level and Low Level Group After Multi Cycles of Treatment

	Therapeutic Efficacy	Baseline sHER2 High Level (132)		Baseline sHER2 Low Level (68)		p	χ^2
		Decreased to Negative (43)	Continuous Positive Group (89)	Continuous Negative Group (31)	Increased to Positive Group (37)
tHER2 negative (98)	CR	0	0	0	0
	PR	4	10	7	1
	SD	4	31	12	19
	PD	0	5	1	4
	ORR	4 (50.00%)	10 (21.74%)	7 (35.00%) ^c	1 (4.17%) ^c	0.008^c	6.972^c
	DCR	8 (100%)	41 (89.13%)	19 (97.73%)	20 (83.33%)
	Total	8	46	20	24
tHER2 positive (102)	CR	0	0	0	1
	PR	22	18	4	4
	SD	13	20	7	8
	PD	0	5	0	0
	ORR	22 (62.86%)	18 (41.86%)	4 (36.36%)	5 (38.46%)
	DCR	35 (100%)	38 (88.37%)	11 (100%)	13 (100%)
	Total	35	43	11	13
	ORR	26 (60.47%) ^a	28 (31.46%) ^a	11 (35.48%)	6 (16.22%)	0.001^a	10.090^a
	DCR	43 (100%) ^b	79 (88.76%) ^b	30 (96.77%)	33 (89.19%)	0.022^b	5.227^b
	Total	43	89	31	37

Notes: ORR= (CR + PR)/Total; DCR = (CR + PR + SD)/Total. ^aComparison of ORR between the sHER2 decreased to negative and the continuous positive group in baseline sHER2 high level patients. ^bComparison of DCR between the sHER2 decreased to negative and the continuous positive group in baseline sHER2 high level patients. ^cComparison of ORR between the sHER2 continuous negative and increase to positive group in baseline sHER2 low level and tHER2 negative patients.

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progress disease; ORR, objective response rate; DCR, disease control rate.

Figure 3 Correlation between the change of sHER2 level and prognosis (TTP) after multiple cycles of treatment. Comparison of TTP between the decrease to negative group and continuous positive group in patients with baseline sHER2 high level (A, p=0.01). Comparison of TTP between the decrease to negative group and continuous positive group in tHER2 positive group (B, p=0.006) and in the tHER2 negative group (C, p=0.684). Comparison of TTP between the continuous negative group and increase to positive group in patients with baseline sHER2 low level (D, p=0.03). Comparison of TTP between the continuous negative group and increase to positive group (E, p=0.055) in the tHER2 positive group and tHER2 negative group (F, p=0.132).

Figure 4 Typical examples of sHER2 dynamic change curve: (A) rapid decline type; (B) stable type; (C) fluctuating type; (D) slow ascending type; (E) slow descending type; (F) spoon type. The ordinate is the value of sHER2 (ng/mL).

Table 5 Clinicopathological Characteristics of Patients and Therapeutic Efficacy in Different Types of sHER2 Dynamic Change Curve

Clinicopathological Characteristics	Rapid Decline	Stable	Fluctuating	Slow Ascending	Slow Descending	Spoon	p	χ^2
Total	25	73	22	17	32	12
Molecular subtype							<0.001	65.954
Luminal A	0	4	2	0	0	0
Luminal B (tHER2 negative)	0	29	11	5	9	3
Luminal B (tHER2 positive)	10	13	1	3	11	2
tHER2 positive	15	12	2	9	11	6
TNBC	0	15	6	0	1	1
ER							0.195	7.360
Negative	16	28	9	8	11	7
Positive	9	45	13	9	21	5
PR							0.545	4.032
Negative	15	32	11	11	14	6
Positive	10	41	11	6	18	6
tHER2							<0.001	53.856
Negative	0	48	19	5	10	4
Positive	25	25	3	12	22	8
sHER2
Low level	0	41	7	10	2	0	<0.001	51.294
High level	25	12	15	7	30	12
Operation approach							0.020	21.163
Radical operation	14	52	17	11	18	6
Non-radical operation	1	9	1	1	1	4
No operation	10	12	4	5	13	2
Liver metastasis							0.022	13.158
Yes	13	12	7	5	13	5
No	12	60	15	12	19	7
Brain metastasis							0.074	10.034
Yes	3	5	6	2	1	1
No	22	68	16	15	31	11

Figure 5 Comparison of prognosis (time to progression, TTP) between different sHER2 dynamic change curves. Pairwise comparison of different curve types found that the TTP of patients in the spoon group was shorter than that of the rapid decline type, stable type, and slow descending type (p=0.028, 0.038, and 0.007, respectively).