The treatment option of progressive disease in breast cancer during neoadjuvant chemotherapy: a single-center experience

Figures & data

Table 1. Pretreatment and post-treatment patient characteristics.

	Pretreatment patient characteristics			Post-treatment patient characteristics
	PD (n = 45, 3.8%)	non-PD (n = 1142, 96.2%)		PD (n = 45, 3.8%)	non-PD (n = 1142, 96.2%)
Characteristic	No. of Patients (%)	No. of Patients (%)	P	No. of Patients (%)	No. of Patients (%)	P
Age, years			.325
Median	48 (-)	49 (-)		-	-
Range	21–65	23–76		-	-
Menopausal status			.180
Premenopausal	30 (66.7)	646 (56.6)		-	-
Postmenopausal	15 (33.3)	496 (43.4)		-	-
Family history of cancer			.497
Breast cancer	2 (4.4)	37 (3.2)		-	-
Other cancers	6 (13.3)	226 (19.8)		-	-
No	37 (82.2)	872 (76.4)		-	-
Unknown	0 (0.0)	7 (0.6)		-	-
BMI ^a			.411
Median	23.2 (-)	23.5 (-)		-	-
Range	14.9–30.8	15.6–34.9		-	-
Ki-67 score ^b			.001
Median	50.00 (-)	30.00 (-)		-	-
Range	5–90	0-95		-	-
ER status			.001
Negative	31 (68.9)	465 (41.5)		-	-
Positive	14 (31.1)	656 (58.5)		-	-
Unknown	0 (0)	21 (1.8)		-	-
PR status			.016
Negative	32 (71.1)	568 (49.7)		-	-
Positive	13 (28.9)	550 (48.2)		-	-
Unknown	0 (0.0)	24 (2.1)		-	-
Her-2 status			.884
Negative	21 (46.7)	563 (49.3)		-	-
Positive	16 (35.6)	416 (36.4)		-	-
Uncertain	6 (13.3)	132 (11.6)		-	-
Unknown	2 (4.4)	31 (2.7)		-	-
Histology			.000
Ductal	34 (75.6)	1074 (94.0)		-	-
Lobular	2 (4.4)	14 (1.2)		-	-
Mixed	5 (11.1)	21 (1.8)		-	-
Other	4 (8.9)	23 (2.0)		-	-
Unknown	0 (0.0)	10 (0.9)		-	-
Nuclear grade			.000
I	0 (0.0)	21 (1.8)		-	-
II	4 (8.9)	217 (19.0)		-	-
III	14 (31.1)	117 (10.2)		-	-
Unknown	27 (60.0)	787 (68.9)		-	-
Tumor size, mm			.133			<.001
Median	38.0 (-)	34.5 (-)		55.0	20.0
Range	13.0–130.0	5.0–160.0		0–230	0–120
T stage			.006			<.001
T0	-	-		1 (2.2)	176 (15.4)
Tis	-	-		0 (0.0)	19 (1.7)
T1	4 (8.9)	77 (6.7)		5 (11.1)	490 (42.9)
T2	19 (42.2)	760 (66.5)		13 (28.9)	356 (31.2)
T3	13 (28.9)	159 (13.9)		13 (28.9)	55 (4.8)
T4	9 (20.0)	146 (12.8)		13 (28.9)	46 (4.0)
N stage			.622			.003
N0	7 (15.6)	136 (11.9)		9 (20.0)	366 (32.0)
N1	28 (62.2)	657 (57.5)		13 (28.9)	325 (28.5)
N2	7 (15.6)	222 (19.4)		6 (13.3)	254 (22.2)
N3	3 (6.7)	127 (11.1)		17 (37.8)	197 (17.3)
AJCC stage			.237			<.001
0	-	-		1 (2.2)	132 (11.6)
IA	0 (0.0)	1 (0.1)		1 (2.2)	153 (13.4)
IIA	8 (17.8)	140 (12.3)		6 (13.3)	269 (23.6)
IIB	12 (26.7)	476 (41.7)		8 (17.8)	117 (10.2)
IIIA	14 (31.1)	272 (23.8)		6 (13.3)	245 (21.5)
IIIB	8 (17.8)	128 (11.2)		6 (13.3)	30 (2.6)
IIIC	3 (6.7)	125 (10.9)		14 (31.1)	196 (17.2)
IV	-	-		3 (6.7)	0 (0.0)
Lymphovascular invasion						.178
Positive	-	-		20 (44.4)	396 (34.7)
Negative	-	-		25 (55.6)	746 (65.3)
Chemotherapy regimen
Anthracycline-based	-	-		37 (82.2)	1016 (89.0)	.161
Taxane-based	-	-		31 (68.9)	1040 (91.1)	.000
Trastuzumab	-	-		2 (4.4)	117 (10.2)	.309
Surgery						.792
BCT	-	-		1 (2.2)	33 (2.9)
Mastectomy	-	-		44 (97.8)	1109 (97.1)

Abbreviations: PD, progressive disease; BMI, body mass index; AJCC, American Joint Committee on Cancer; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2; BCT, breast-conserving therapy.

^aBMI was available in 45 patients in the PD group and 1136 patients in the non-PD group.

^bKi-67 scores were available in 27 patients in the PD group and 712 patients in the non-PD group.

Figure 1. Timing of PD/SD/response on NACT.

Figure 2. (a) Overall survival of the two salvage therapies (surgery and chemotherapy). (b) Disease-free survival of the two salvage therapies (surgery and chemotherapy. (c) Overall survival and (d) disease-free survival of patients with progression disease(PD) and pathological complete response (pCR). (e) Overall survival and (f) disease-free survival of patients with PD and non-PD.

Table 2. Patients’ and tumor characteristics of PD and pCR.

	PD (n = 45, 3.8%)		pCR (n = 133, 11.2%)
Factor	No. of Patients	%	No. of Patients	%	P
Age, years					.352
Median	48		49
Range	21–65		26–69
Menopausal status					.142
Premenopausal	30	66.7	61	45.9
postmenopausal	15	33.3	72	54.1
Family history of cancer					.154
Breast cancer	1	2.2	8	6.1
Other cancers	6	13.3	31	23.3
No	38	84.4	94	70.7
BMI
Median	23.191		23.437		.517
Range	14.9–30.8		16.61–31.64
Tumor size, mm					.015
Median	38.0		31.0
Range	13.0–130.0		9.0–145.0
T stage					<.001
T1	4	8.9	16	12.0
T2	19	42.2	96	72.2
T3	13	28.9	13	9.8
T4	9	20.0	8	6.0
N stage					.553
N0	7	15.6	20	15.0
N1	27	60.0	68	51.1
N2	7	15.6	34	25.6
N3	4	8.9	11	8.3
AJCC stage					.289
IA‎/IIA	8	17.8	26	19.5
IIB‎/IIIA	26	57.8	88	66.2
IIIB‎/IIIC	11	24.4	19	14.3
Histology					<.001
Ductal	34	75.6	127	95.5
Lobular	2	4.4	1	0.8
Mixed	5	11.1	0	0.0
Other	4	8.9	2	1.5
Unknown	0	0.0	3	2.3
Nuclear grade					.549
I	0	0.0	0	0.0
II	4	8.9	6	4.5
III	14	31.1	10	7.5
Unknown	27	60.0	117	88.0
TOPO II					.637
Negative	3	6.7	4	3.0
Positive	25	55.6	68	51.1
Unknown	17	37.8	61	45.9
Ki-67 score ^a
Median	50.00		40.00		.130
Range	5–90		1–90
ER status					.477
Negative	31	68.9	80	60.2
Positive	14	31.1	47	35.3
Unknown	0	0	6	4.5
PR status					.986
Negative	32	71.1	88	66.2
Positive	13	28.9	38	28.6
Unknown	0	0.0	7	5.3
Her-2					.149
Negative	21	46.7	53	39.8
Positive	16	35.6	64	48.1
Uncertain	6	13.3	8	6.0
Unknown	2	0	8	6.0
Chemotherapy regimen
Anthracycline-based	37	82.2	104	78.2	.565
Taxane-based	31	68.9	127	95.5	<.001
Trastuzumab	2	4.4	42	31.6	<.001
Surgery					.542
BCT	1	2.2	8	6.0
Mastectomy	44	97.8	125	94.0

Abbreviations: PD, progressive disease; pCR, pathological complete response; BMI, body mass index; AJCC, American Joint Committee on Cancer; TOPO, topoisomerase; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2; BCT, breast-conserving therapy.

^aKi-67 scores were available in 27 patients in the PD group and 107 patients in the pCR group.

Figure 3. (a) Tumor response in HER2+ patients receiving NACT with or without trastuzumab. (b) Evaluation of tumor response in different tumor subtypes.

Table 3. Predictors of PD.

	Univariate Analysis		Multivariate Analysis
Factor	OR (95% CI)	P	OR (95% CI)	P
Age	0.98 (0.95, 1.02)	.325
BMI	0.96 (0.87, 1.05)	.341
Family history of cancer		.498
No	1.00	-
Breast cancer	0.62 (.08, 4.64)	.642
Other cancers	0.61 (0.25, 1.45)	.266
Menopausal status
Premenopausal	1.00	-
Postmenopausal	0.65 (0.35, 1.22)	.183
Prechemotherapy size	1.01 (1.00, 1.03)	.044
Prechemotherapy T stage		.009
T1	1.00	-
T2	0.48 (0.16, 1.45)	.19
T3	1.57 (0.50, 4.99)	.441
T4	1.19 (0.35, 3.98)	.782
Prechemotherapy N stage		.790
N0	1.00	-
N1	0.80 (0.34, 1.87)	.604
N2	0.61 (0.21, 1.79)	.369
N3	0.61 (0.18, 2.14)	.442
Prechemotherapy AJCC stage		.474
IA‎/IIA	1.00	-
IIB‎/IIIA	0.61 (0.27, 1.38)	.237
IIIB‎/IIIC	0.77 (0.30, 1.95)	.576
ER status
Negative	1.00	-
Positive	0.32 (0.17, 0.61)	.001
PR status
Negative	1.00	-
Positive	0.42 (0.22, 0.81)	.009
HER2 status
Negative	1.00
Positive	1.03 (0.53, 2.00)	.928
Histology		<.001
Ductal	1.00	-
Lobular	4.24 (0.93, 19.26)	.062
Mixed	11.35 (3.87, 33.30)	.000
Others	5.52 (1.81, 16.85)	.003
Nuclear grade
1/2	1.00	-	1.00	-
3	7.03 (2.26, 21.83)	.001	5.05 (1.18, 21.61)	.029
Ki-67 score	1.03 (1.01, 1.04)	.001	1.03 (1.00, 1.06)	.047
Anthracycline-based regimen	0.57 (0.26, 1.26)	.166
Taxane-based regimen	0.22 (0.11, 0.42)	<.001
Trastuzumab therapy	0.41 (0.10, 1.70)	.219

Abbreviations: PD, progressive disease; OR, Odds Ratio; BMI, body mass index; AJCC, American Joint Committee on Cancer; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2.

Table 4. Univariate and multivariate effects of potentially prognostic factors on OS and DFS.

	Predictors of Overall survival				Predictors of Disease-free survival
	Univariate Analysis		Multivariate Analysis		Univariate Analysis		Multivariate Analysis
Prognostic factor	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Response status
Non-PD	1.00	-	1.00	-	1.00	-	1.00
PD	3.85 (2.45, 6.05)	<.001	3.85 (1.77, 8.35)	.001	3.00 (2.04, 4.42)	<.001	3.77(1.77, 8.00)	.001
Age	0.99 (0.98, 1.02)	.855			0.99 (0.98, 1.01)	.176
BMI	0.95 (0.90, 0.99)	.015			0.96 (0.93, 0.99)	.036
Family history of cancer
No	1.00	-			1.00
Breast cancer	0.37 (0.12, 1.15)	.09			0.61 (0.30, 1.23)	.166
Other cancers	0.76 (0.52, 1.11)	.159			0.86 (0.65, 1.13)	.284
Menopausal status
Premenopausal	1.00	-			1.00
Postmenopausal	1.07 (0.81, 1.41)	.635			0.86 (0.70, 1.07)	.181
Prechemotherapy size	1.02 (1.02, 1.03)	<.001	1.01 (1.00, 1.03)	.035	1.02 (1.02, 1.03)	<.001	1.02 (1.00, 1.03)	.010
Prechemotherapy T stage
T1	1.00	-			1.00	-
T2	1.16 (0.59, 2.29)	.673			1.17 (0.71, 1.92)	.544
T3	3.12 (1.53, 6.34)	.002			2.89 (1.71, 4.88)	<.001
T4	2.94 (1.44, 6.02)	.003			2.55 (1.50, 4.34)	.001
Prechemotherapy N stage
N0	1.00	-	1.00	-	1.00	-	1.00	-
N1	1.29 (0.77, 2.15)	.339	1.14 (0.44, 2.98)	.784	1.52 (1.02, 2.28)	.041	0.97 (0.34, 2.76)	.954
N2	1.49 (0.84, 2.64)	.175	1.21 (0.42, 3.44)	.727	1.74 (1.11, 2.72)	.016	1.54 (0.52, 4.60)	.437
N3	4.17 (2.39, 7.28)	<.001	3.07 (1.10, 8.58)	.032	4.70 (3.02, 7.33)	<.001	3.14 (1.05, 9.35)	.040
Prechemotherapy AJCC stage
IA‎/IIA	1.00	-			1.00	-
IIB‎/IIIA	1.77 (0.99, 3.14)	.052			2.01 (1.29, 3.11)	.002
IIIB‎/IIIC	4.23 (2.35, 7.62)	<.001			4.57 (2.90, 7.19)	<.001
ER status
Negative	1.00	-	1.00	-	1.00	-	1.00	-
Positive	0.59 (0.45, 0.78)	<.001	0.42 (0.25, 0.72)	.001	0.68 (0.55, 0.84)	<.001	0.47 (0.29, 0.76)	.002
PR status
Negative	1.00	-			1.00	-
Positive	0.61 (0.46, 0.81)	.001			0.66 (0.54, 0.82)	<.001
HER2 status
Negative	1.00	-			1.00	-
Positive	1.03 (0.77, 1.40)	.826			0.91 (0.73, 1.15)	.431
Histology		.523
Ductal	1.00	-			1.00	-
Lobular	1.84 (0.68, 4.951)	.230			0.88 (0.33, 2.37)	.805
Mixed	1.45 (0.64, 3.27)	.369			0.94 (0.44, 1.98)	.866
Others	1.12 (0.50, 2.53)	.786			1.24 (0.68, 2.27)	.480
Lymphovascular invasion
Negative	1.00	-			1.00	-	1.00	-
Positive	2.09 (1.59, 2.76)	<.001			1.99 (1.61, 2.45)	<.001	1.90 (1.19, 3.05)	.008
Nuclear grade						.008
1	1.00	-	1.00	-	1.00	-
2	4.26 (0.58, 31.21)	.154	4.24 (0.57, 31.44)	.158	2.58 (0.81, 8.22)	.110
3	10.88 (1.48, 80.01)	.019	6.12 (0.80, 46.68)	.080	4.13 (1.28, 13.32)	.018
Ki-67 score	1.01 (0.99, 1.01)	.197			1.01 (1.00, 1.01)	.028
Anthracycline-based regimen	1.46 (0.83, 2.56)	.188			1.06 (0.73, 1.55)	.758
Taxane-based regimen	1.28 (0.63, 2.59)	.498			1.40 (0.81, 2.44)	.233
Trastuzumab therapy	0.39 (0.19, 0.79)	.009	0.10 (0.01, 0.73)	.023	0.55 (0.35, 0.84)	.006

Abbreviations: HR, Hazard Ratio; PD, progressive disease; BMI, body mass index; AJCC, American Joint Committee on Cancer; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2.