Potential clinically useful prognostic biomarkers in triple-negative breast cancer: preliminary results of a retrospective analysis

Figures & data

Table 1 Baseline characteristics in the general population and in non-TNBC vs TNBC population

Variables/population	BC population 631 (100%)		Non-TNBC 546 (86.5%)		TNBC 85 (13.5%)		P-value
	No	%	No	%	No	%
Age (years)/mean/range	53.7	[24–81]	53.9	[28–81]	52.2	[24–80]	0.205
Menopausal status
Premenopausal	130	20.60	106	19.41	24	28.24	0.061
Postmenopausal	501	79.40	440	80.59	61	71.76
Quadrant
External	372	58.95	326	59.71	46	54.12	0.001
Internal	172	27.26	136	24.91	36	42.35
Central	87	13.79	84	15.38	3	3.53
Clinical stage
I	121	19.18	111	20.33	10	11.76	0.068
II A, II B	500	79.24	425	77.84	75	88.24
III A, III B	10	1.58	10	1.83	0	0.00
Type of surgery
Sectorectomy	183	29.00	149	27.29	34	40.00	0.016
Mastectomy	448	71.00	397	72.71	51	60.00
Histopathology type
IDC	518	82.09	438	80.22	80	94.12	0.001
ILC	38	6.02	38	6.96	0	0.00
Mixed IDC/ILC	60	9.51	60	10.99	0	0.00
Other type	15	2.38	10	1.83	5	5.88
pT
pT1a	21	3.33	21	3.85	0	0.00	0.008
pT1b, pT1c	292	46.28	261	47.80	31	36.47
pT2	277	43.90	226	41.39	51	60.00
pT3	7	1.11	7	1.28	0	0.00
pT4	11	1.74	11	2.01	0	0.00
Unknown	23	3.65	20	3.66	3	3.53
Histologic grade
G1	46	7.29	44	8.06	2	2.35	0.001
G2	346	54.83	328	60.07	18	21.18
G3	212	33.60	149	27.29	63	74.12
Unknown	27	4.28	25	4.58	2	2.35
pN
0	367	58.16	311	56.96	56	65.88	0.354
1a	185	29.32	163	29.85	22	25.88
2a	58	9.19	52	9.52	6	7.06
3a	21	3.33	20	3.66	1	1.18
Lymphovascular invasion
No	550	87.16	476	87.18	74	87.06	0.732
Yes	35	5.55	31	5.68	4	4.71
Unknown	46	7.29	39	7.14	7	8.24
In situ pattern
No	513	81.30	439	80.40	74	87.06	0.148
Yes	91	14.42	83	15.20	8	9.41
Unknown	27	4.28	24	4.40	3	3.53
HER2 expression
Negative	366	58.00	295	54.03	71	83.53	0.001
1+	147	23.30	137	25.09	10	11.76
2+ ISH negative	61	9.67	57	10.44	4	4.71
2+ ISH positive	22	3.49	22	4.03	0	0.00
Positive	35	5.55	35	6.41	0	0.00
Ki67
<20%	329	52.14	314	57.51	15	17.65	0.001
20%–60%	266	42.16	216	39.56	50	58.82
>60%	36	5.71	16	2.93	20	23.53
Cytotoxic regimen
Antr only	344	54.52	300	54.95	44	51.76	0.219
Antr and Tax	150	23.77	127	23.26	23	27.06
Tax only	13	2.06	9	1.65	4	4.71
Other regimens	124	19.65	110	20.15	14	16.47
Relapse
No	525	83.20	458	83.88	67	78.82	0.246
Yes	106	16.80	88	16.12	18	21.18

Abbreviations: Antr, anthracyclines; BC, breast cancer; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; ISH, in situ hybridization; pN, regional lymph node; pT, primary tumor; Tax, taxanes; TNBC, triple-negative breast cancer.

Table 2 Correlation of CK5/6, EGFR, and E-cad with clinical and pathological variables in the TNBC population

Variable/Biomarker	CK5/6 n (%)		P-value	EGFR n (%)		P-value	E-cad n (%)		P-value
	Negative	Positive		Negative	Positive		Negative	Positive
	21 (45.6%)	25 (54.4%)		27 (43.5%)	35 (54.5%)		17 (38.6%)	27 (61.4%)
Quadrant
External	8 (38.1)	16 (64)	0.207	16 (59.3)	18 (51.4)	0.808	9 (52.9)	14 (51.9)	0.342
Internal	11 (52.4)	8 (32)		10 (37)	15 (42.9)		8 (47.1)	10 (37)
Central	2 (9.5)	1 (4)		1 (3.7)	2 (5.7)		0 (0)	3 (11.1)
Clinical stage
I	5 (23.8)	0 (0)	0.010	3 (11.1)	2 (5.7)	0.439	5 (29.4)	1 (3.7)	0.016
II A, II B	16 (76.2)	25 (100)		24 (88.9)	33 (94.3)		12 (70.6)	26 (96.3)
III A, III B	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Histopathology type
IDC	18 (85.7)	23 (92)	0.495	27 (100)	30 (85.7)	0.041	15 (88.2)	24 (88.9)	0.947
ILC	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Mixed IDC/ILC	3 (14.3)	2 (8)		0 (0)	0 (0)		0 (0)	0 (0)
Other type	0 (0)	0 (0)		0 (0)	5 (14.3)		2 (11.8)	3 (11.1)
pT
pT1a	0 (0)	0 (0)	0.521	0 (0)	0 (0)	0.789	0 (0)	0 (0)	0.734
pT1b, pT1c	8 (38.1)	6 (26.1)		9 (33.3)	13 (37.1)		6 (40)	8 (29.6)
pT2	13 (61.9)	17 (73.9)		18 (66.7)	20 (57.1)		9 (60)	18 (66.7)
pT3	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
pT4	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Unknown	0 (0)	0 (0)		0 (0)	2 (5.8)		0 (0)	1 (3.7)
MC/MF
No	21 (100)	22 (88)	0.101	25 (92.6)	32 (91.4)	0.867	15 (88.2)	25 (92.6)	0.624
Yes	0 (0)	3 (12)		2 (7.4)	3 (8.6)		2 (11.8)	2 (7.4)
Histologic grade
G1	0 (0)	2 (8)	0.096	2 (7.4)	0 (0)	0.115	0 (0)	2 (7.4)	0.429
G2	6 (28.6)	2 (8)		9 (33.3)	7 (20)		3 (17.6)	6 (22.2)
G3	15 (71.4)	21 (84)		16 (59.3)	27 (77.1)		14 (82.4)	18 (66.7)
Unknown	0 (0)	0 (0)		0 (0)	1 (2.9)		0 (0)	1 (3.7)
pN
0	15 (71.4)	14 (56)	0.277	17 (63)	22 (62.9)	0.178	10 (58.8)	18 (66.7)	0.354
1a	5 (23.8)	9 (36)		10 (37)	8 (22.9)		6 (35.3)	7 (25.9)
2a	0 (0)	2 (8)		0 (0)	4 (11.4)		0 (0)	2 (7.4)
3a	1 (4.8)	0 (0)		0 (0)	1 (2.8)		1 (5.9)	0 (0)
Capsular effraction
No	17 (81)	18 (72)	0.514	21 (77.8)	30 (85.7)	0.417	14 (82.4)	22 (81.5)	0.942
Yes	4 (19)	7 (28)		6 (22.2)	5 (14.3)		3 (17.6)	5 (18.5)
Lymphovascular invasion
No	19 (90.5)	21 (84)	–	25 (92.6)	29 (82.9)	0.886	13 (86.4)	22 (81.5)	0.285
Yes	0 (0)	0 (0)		2 (7.4)	2 (5.7)		0 (0)	2 (7.4)
Unknown	2 (9.5)	4 (16)		0 (0)	4 (11.4)		4 (23.6)	3 (11.1)
In situ pattern
No	18 (85.7)	22 (88)	0.252	25 (92.6)	30 (85.7)	0.814	12 (70.6)	23 (85.2)	0.460
Yes	3 (14.3)	1 (4)		2 (7.4)	3 (8.6)		3 (17.6)	3 (11.1)
Unknown	0 (0)	2 (8)		0 (0)	2 (5.7)		2 (11.8)	1 (3.7)
Relapse
No	12 (57.1)	23 (92)	0.013	23 (85.2)	26 (74.3)	0.358	12 (70.6)	21 (77.8)	0.592
Yes	9 (42.9)	2 (8)		4 (14.8)	9 (25.7)		5 (29.4)	6 (22.2)
Total	46			62			44

Abbreviations: CK5/6, cytokeratin 5/6; E-cad, E-cadherin; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; MC/MF, multicentric/multifocal; pN, regional lymph node; pT, primary tumor; TNBC, triple-negative breast cancer.

Table 3 Correlation of Bcl2, Cox-2, p53, and TOP2A with clinical and pathological variables in the TNBC population

Variable/Biomarker	Bcl2 n (%)		P-value	Cox-2 n (%)		P-value	p53 n (%)		P-value	TOP2A n (%)		P-value
	Negative	Positive		Negative	Positive		Negative	Positive		Negative	Positive
	26 (44.1)	33 (55.9)		29 (63.1)	17 (36.9)		22 (33.8)	43 (66.2)		34 (54.8)	28 (45.2)
Quadrant
External	14 (53.8)	23 (69.7)	0.182	15 (51.7)	10 (58.8)	0.897	11 (50.0)	23 (53.5)	0.044	19 (55.9)	19 (67.9)	0.338
Internal	10 (38.5)	10 (30.3)		12 (41.4)	6 (35.3)		8 (36.4)	20 (46.5)		13 (38.2)	9 (32.1)
Central	2 (7.7)	0 (0)		2 (6.9)	1 (5.9)		3 (13.6)	0 (0)		2 (5.9)	0 (0)
Clinical stage
I	3 (11.5)	0 (0)	0.080	6 (20.7)	1 (5.9)	0.177	2 (9.1)	5 (11.6)	0.755	1 (2.9)	2 (7.1)	0.585
II A, II B	23 (88.5)	33 (100)		23 (79.3)	16 (94.1)		20 (90.9)	38 (88.4)		33 (97.1)	26 (92.9)
III A, III B	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Histopathology type
IDC	24 (92.3)	30 (90.9)	1.000	27 (93.1)	16 (94.1)	0.893	21 (95.5)	39 (90.7)	0.496	32 (94.1)	25 (89.3)	0.487
ILC	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Mixed IDC/ILC	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Other type	2 (7.7)	3 (9.1)		2 (6.9)	1 (5.9)		1 (4.5)	4 (9.3)		2 (5.9)	3 (10.7)
pT
pT1a	0 (0)	0 (0)	0.543	0 (0)	0 (0)	0.342	0 (0)	0 (0)	0.584	0 (0)	0 (0)	0.431
pT1b, pT1c	13 (50.0)	13 (39.3)		12 (41.3)	4 (23.5)		9 (40.9)	13 (30.2)		11 (32.3)	13 (46.4)
pT2	13 (50.0)	18 (54.5)		16 (55.1)	11 (64.7)		13 (59.1)	27 (62.7)		21 (61.7)	15 (53.6)
pT3	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
pT4	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)
Unknown	0 (0)	2 (6.0)		1 (3.4)	2 (11.7)		0 (0)	3 (6.9)		2 (5.8)	0 (0)
MC/MF
No	26 (100)	30 (90.9)	0.115	27 (93.1)	14 (82.4)	0.258	21 (95.5)	39 (90.7)	0.496	32 (94.1)	27 (96.4)	0.673
Yes	0 (0)	3 (9.1)		2 (6.9)	3 (17.6)		1 (4.5)	4 (9.3)		2 (5.9)	1 (3.6)
Histologic grade
G1	2 (7.7)	0 (0)	0.280	2 (6.8)	0 (0)	0.483	0 (0)	0 (0)	0.530	2 (5.9)	0 (0)	0.133
G2	3 (11.5)	4 (12.1)		6 (20.6)	3 (17.6)		6 (27.3)	8 (18.6)		7 (20.6)	2 (7.1)
G3	21 (80.8)	28 (84.8)		20 (68.9)	14 (82.4)		16 (72.7)	34 (79.0)		25 (73.5)	25 (89.2)
Unknown	0 (0)	1 (3.0)		1 (3.4)	0 (0)		0 (0)	1 (2.3)		0 (0)	1 (3.5)
pN
0	16 (61.5)	21 (63.6)	0.142	18 (62.1)	12 (70.6)	0.595	18 (81.8)	28 (65.1)	0.111	23 (67.6)	16 (57.1)	0.639
1a	10 (38.5)	7 (21.2)		8 (27.6)	5 (29.4)		3 (13.6)	9 (20.9)		9 (26.5)	9 (32.1)
2a	0 (0)	4 (12.1)		2 (6.9)	0 (0)		0 (0)	6 (14.0)		2 (5.9)	2 (7.1)
3a	0 (0)	1 (3.0)		1 (3.4)	0 (0)		1 (4.5)	0 (0)		0 (0)	1 (3.6)
Capsular effraction
No	20 (76.9)	25 (75.8)	1.000	20 (69.0)	16 (94.1)	0.046	18 (81.8)	36 (83.7)	0.846	27 (79.4)	20 (71.4)	0.557
Yes	6 (23.1)	8 (24.2)		9 (31.0)	1 (5.9)		4 (18.2)	7 (16.3)		7 (20.6)	8 (28.6)
Lymphovascular invasion
No	24 (92.3)	29 (87.8)	–	22 (75.8)	15 (88.2)	0.251	20 (86.4)	34 (79.1)	0.133	32 (94.1)	24 (85.7)	–
Yes	0 (0)	0 (0)		2 (6.8)	0 (0)		0 (0)	4 (9.3)		0 (0)	0 (0)
Unknown	2 (7.7)	4 (12.2)		5 (17.2)	2 (11.8)		2 (13.6)	5 (11.6)		2 (5.9)	4 (14.3)
In situ pattern
No	22 (84.6)	30 (90.9)	0.106	23 (79.3)	14 (82.4)	0.313	19 (86.4)	35 (81.3)	0.898	32 (94.1)	23 (82.1)	0.013
Yes	4 (15.4)	1 (3.0)		5 (17.2)	1 (5.9)		3 (13.6)	5 (11.6)		0 (0)	5 (17.9)
Unknown	0 (0)	2 (6.0)		1 (3.4)	2 (11.7)		0 (0)	3 (7.0)		2 (5.9)	0 (0)
Relapse
No	19 (73.1)	26 (78.8)	0.760	21 (72.4)	14 (82.4)	0.446	15 (68.2)	36 (83.7)	0.149	29 (85.3)	20 (71.4)	0.220
Yes	7 (26.9)	7 (21.2)		8 (27.6)	3 (17.6)		7 (31.8)	7 (16.3)		5 (14.7)	8 (28.6)
Total	59		46		65		62

Abbreviations: Bcl2, B-cell lymphoma 2; Cox-2, cyclooxygenase-2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; MC/MF, multicentric/multifocal; pN, regional lymph node; pT, primary tumor; TNBC, triple-negative breast cancer; TOP2A, topoisomerase II alpha.

Figure 1 Kaplan–Meier curves in non-TNBC and TNBC subgroups.

Abbreviations: EFS, event-free survival; TNBC, triple-negative breast cancer.

Figure 2 Kaplan–Meier curves in IHC surrogate phenotypes BC population.

Abbreviations: BC, breast cancer; EFS, event-free survival; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemical; TNBC, triple-negative breast cancer.

Figure 3 Kaplan–Meier curves according to the CK5/6 expression in TNBC patients.

Abbreviations: CK5/6, cytokeratin 5/6; EFS, event-free survival; TNBC, triple-negative breast cancer.

Figure 4 Kaplan–Meier curves in subgroups according to the CK5/6–E-cad score in TNBC patients.

Abbreviations: CK5/6, cytokeratin 5/6; E-cad, E-cadherin; Neg, negative; Pos, positive; TNBC, triple-negative breast cancer.