Prognostic predictive value of Ki-67 in stage I–II triple-negative breast cancer

Figures & data

Table 1. Patients' characteristics and treatments.

Characteristics (n = 1146)	Low Ki-67 (≤45) N%	High Ki-67 (>45) N%	p-value	Total
Age			<0.001
≤50	235 (54.7%)	503 (70.3%)		738 (64.4%)
>50	195 (45.3%)	213 (29.7%)		408 (35.6%)
Menstrual state			<0.001
Premenopause	235 (54.7%)	496 (69.3%)		731 (63.8%)
Postmenopause	195 (45%)	220 (30.7%)		415 (36.2%)
Tumor location			0.952
Left	223 (51.9%)	370 (51.7%)		593 (51.7%)
Right	207 (48.1%)	346 (48.3%)		553 (48.3%)
Breast surgery			0.727
Breast-conserving surgery	100 (23.2%)	173 (24.2%)		273 (23.8%)
Mastectomy	330 (76.7%)	543 (75.8%)		873 (76.2%)
Axillary surgery			0.771
Sentinel lymph node biopsy	109(25.3%)	176(24.6%)		285(24.9%)
Axillary lymph node dissection	321(74.7%)	540(75.4%)		861(75.1%)
Intravascular cancer thrombus			0.877
Yes	95 (22.1%)	161 (22.5%)		256 (22.3%)
No	335 (77.9%)	555 (77.5%)		890 (77.7%)
Nerve tract invasion			0.317
Yes	33 (7.7%)	44 (6.1%)		77 (6.7%)
No	397 (92.3%)	672 (93.9%)		1069 (93.3%)
Extrinsic lymph node invasion			0.766
Yes	5 (1.2%)	7 (1.0%)		12 (1.0%)
No	425 (98.8%)	709 (99.0%)		1134 (99.0%)
Histology stage			<0.001
II	152 (35.3%)	82 (11.4%)		234 (20.4%)
III	221 (51.4%)	559 (78.1%)		780 (68.1%)
Other types	57 (13.3%)	75 (10.5%)		132 (11.5%)
Lymph node stage			0.292
N0	290 (67.4%)	461 (64.4%)		751 (65.5%)
N1	140 (32.6%)	255 (35.6%)		395 (34.5%)
Tumor stage			0.178
T1	175 (40.7%)	256 (35.8%)		431 (37.6%)
T2	248 (57.7%)	442 (61.7%)		690 (66.2%)
T3	7 (1.6%)	18 (2.5%)		25 (2.2%)
TNM stage^1			0.082
I	129 (30.0%)	181 (25.3%)		310 (27.1%)
II	301 (70.0%)	535 (74.7%)		836 (72.9%)
Neoadjuvant chemotherapy			0.904
Yes	66 (15.3%)	108 (15.1%)		174 (15.2%)
No	364 (84.7%)	608 (84.9%)		972 (84.8%)
Postoperative chemotherapy			0.019
Yes	364 (84.7%)	640 (89.4%)		1004 (87.6%)
No	66 (15.3%)	76 (10.6%)		142 (12.4%)
Radiotherapy			0.735
Yes	174 (40.5%)	297 (41.5%)		471 (41.1%)
No	256 (59.5%)	419 (58.5%)		675 (58.9%)
Total	430	716		1146

1 TNM staging is based on the American Joint Committee on Cancer 8th.

N0: No lymph node metastases; N1: One to three axillary lymph node metastases; T1: The tumor is ≤2 cm in length; T2: The tumor is >2 cm or ≤5 cm in length; T2: The tumor is >2 cm or ≤5 cm in length.

Table 2. Neoadjuvant chemotherapy information.

Characteristics		Low Ki-67 (≤45%)	High Ki-67 (>45%)	Chi-square p-value	Total (n = 174)
NACT	Yes	66 (37.9%)	108 (62.1%)	0.904	174
	No	364 (37.4%)	608 (62.6%)		972
NACT Ki-67 biopsy	Low	58 (78.4%)	16 (21.6%)	<0.001	74 (42.5%)
	High	8 (8.0%)	92 (92.0%)		100 (57.5%)
Ki-67 change	Decrease	37 (33.0%)	75 (67.0%)	0.025	112 (64.4%)
	Increase	13 (36.1%)	23 (63.9%)		36 (20.7%)
	No changes	16 (61.5%)	10 (38.5%)		26 (14.9%
NACT pCR	Yes	30 (31.9%)	64 (68.1%)	0.076	94 (54.0%)
	No	36 (45.0%)	44 (55.0%)		80 (46.0%)

NACT: Neoadjuvant chemotherapy; pCR: Pathological complete response.

Table 3. Recurrence, metastasis and death.

	Low Ki-67 (≤45%) N%	High Ki-67 (>45%) N%	p-value	Total
Primary events			0.076
Yes	80 (18.6%)	165 (23.0%)		245 (21.4%)
No	350 (81.4%)	551 (77.0%)		901 (78.6%)
Death
Yes	59 (13.7%)	122 (17.0%)	0.136	181 (15.8%)
No	371 (86.3%)	594 (83.0%)		965 (84.2%)
Total	430	716		1146

Primary events were defined as pathological or radiological diagnoses of recurrence, metastasis, or BC-related death.

Figure 1. Kaplan-Meier survival curve in triple-negative breast cancer patients.

High Ki-67 expression index was remarkably linked with poorer DFS (log-rank p = 0.039; Figure 1A) and OS (log-rank p = 0.029; Figure 1B). The lymph node stage was also substantially correlated with worse DFS (log-rank p < 0.001; Figure 1C) and OS (log-rank p < 0.001; Figure 1D). (A) Disease-free survival curve of the Ki-67 group; (B) overall Survival curve of the Ki-67 group; (C) disease-free survival curve of the lymph node stage group; (D) overall survival curve of the lymph node stage group.

DFS: Disease-free survival; N0: no lymph node metastases; N1: One to three axillary lymph node metastases; OS: Overall survival.

Table 4. The Univariate and Multivariate Analysis of DFS and OS.

A. Univariate and multivariate analysis of DFS.
Variables	DFS	Univariate			Multivariate
		HR	95% CI	p-value	HR	95% CI	p-value
Age (years)	≤50 vs >50	0.897	0.688–1.170	0.424
Menstrual state	Pre vs post	0.889	0.682–1.159	0.384
Tumor location	Left vs right	1.018	0.792–1.307	0.892
Breast surgery	BCS vs mastectomy	0.937	0.700–1.254	0.661
Axillary surgery	SLNB vs ALND	1.050	0.782–1.409	0.747
Ki-67	Low vs high	1.323	1.013–1.729	0.040	1.357	1.017–1.810	0.038
Intravascular cancer thrombus	Yes vs no	0.752	0.567–0.997	0.047	0.876	0.645–1.189	0.396
Nerve tract invasion	Yes vs no	0.585	0.387–0.885	0.011	0.632	0.411–0.973	0.037
Extrinsic lymph node invasion	Yes vs no	0.336	0.149–0.756	0.008	0.661	0.285–1.533	0.335
Histology stage	II vs III	0.817	0.602–1.108	0.193	0.663	0.486–0.933	0.017
	II vs other types	1.070	0.696–1.646	0.757	1.058	0.680–1.646	0.802
Lymph node stage	N0 vs N1	1.760	1,370-2.263	<0.001	3.845	2.684–5.508	<0.001
Tumor stage	T1 vs T2	1.283	0.979–1.680	0.070	1.301	0.856–1.976	0.218
	T1 vs T3	1.718	0.793–3.722	0.170	2.963	1.228–7.152	0.016
TNM stage	I vs II	1.446	1.062–1.969	0.019	0.791	0.466–1.343	0.385
Neoadjuvant chemotherapy	Yes vs no	1.573	1.047–2.362	0.029	2.240	1.434–3.500	<0.001
Postoperative chemotherapy	Yes vs no	1.163	0.806–1.679	0.420	1.152	0.774–1.686	0.468
Radiotherapy	Yes vs no	1.439	1.103–1.878	0.007	2.457	1.770–3.409	<0.001
B. Univariate and multivariate analysis of OS.
Variables	OS	Univariate			Multivariate
		HR	95% CI	p-value	HR	95% CI	p-value
Age (year)	≤50 vs >50	0.970	0.714–1.318	0.846
Menstrual state	Pre vs post	0.965	0.711–1.308	0.816
Tumor location	Left vs right	1.100	0.822–1.473	0.520
Breast surgery	BCS vs mastectomy	1.133	0.789–1.627	0.498
Axillary surgery	SLNB vs ALND	1.065	0.749–1.513	0.727
Ki-67	Low vs high	1.413	1.035–1.929	0.030	1.412	1.011–1.972	0.043
Intravascular cancer thrombus	Yes vs no	0.680	0.493–0.939	0.019	0.798	0.563–1.131	0.205
Nerve tract invasion	Yes vs no	0.635	0.390–1.033	0.068	0.706	0.424–1.173	0.179
Extrinsic lymph node invasion	yes vs no	0.247	0.109–0.558	<0.001	0.617	0.263–1.449	0.268
Histology stage	II vs III	0.826	0.578–1.179	0.292	0.699	0.479–1.021	0.064
	II vs other types	1.065	0.647–1.751	0.805	1.127	0.674–1.885	0.647
Lymph node stage	N0 vs N1	2.139	1.598–2.863	<0.001	5.458	3.628–8.211	<0.001
Tumor stage	T1 vs T2	1.341	0.978–1.839	0.068	1.461	0.909–2.349	0.117
	T1 vs T3	1.280	0.465–3.529	0.633	2.654	0.862–8.169	0.089
TNM stage	I vs II	1.486	1.032–2.141	0.033	0.658	0.358–1.208	0.177
Neoadjuvant chemotherapy	Yes vs no	1.997	1.195–3.337	0.008	3.102	1.789–5.380	<0.001
Postoperative chemotherapy	Yes vs no	1.188	0.779–1.813	0.424	1.206	0.775–1.877	0.407
Radiotherapy	Yes vs no	1.447	1.060–1.974	0.020	2.788	1.906–4.077	<0.001

TNM staging is based on the American Joint Committee on Cancer 8th.

ALND: Axillary lymph node dissection; BCS: Breast-conserving surgery; DFS: Disease-free survival; OS: Overall survival; Pre: Premenopause; Post: Postmenopause; SLNB: Sentinel lymph node biopsy.

Figure 2. Subgroups of the univariate and multivariate analysis in the Ki-67 high group and N0 group.

The adjusted p-value and hazard ratio were obtained from the Cox regression model. (A) Analysis for disease-free survival in the Ki-67 high group; (B) analysis for overall survival in the Ki-67 high group; (C) analysis for disease-free survival in the N0 group; (D) analysis for overall survival in the N0 group.

DFS: Disease-free survival; ELNI: Extra lymph node invasion; HR: Hazard ratio; ICT: Intravascular cancer thrombosis; N0: No lymph node metastases; NACT: Neoadjuvant chemotherapy; NTI: Nerve tract invasion; OS: Overall survival; POCT: Postoperative chemotherapy.