Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy

Table 1 Clinical-pathological features n (%)

	Cases	sTIL ≥ 50%	P value	pCR	P value	Overall Survival at 5 yr(OS = 50.1%)	P value	Progression free survival at 5 yr(DFS = 57.8%)	P value
	435	181		48
Age (yr), median (range)	49 (24-84)	49 (24-84)	0.923	47 (28-80)	0.472		0.512		0.833
< 50	231 (53.1)	96 (35.2)		28 (12.1)		48.8%		59.7%
≥ 50	204 (46.9)	85 (36.7)		20 (9.8)		51.7%		55.9%
Histological subtypes			0.928		0.234		0.512		0.497
Ductal	406 (93.3)	169 (43.6)		43 (10.6)		49.0%		57.5%
Lobular	21 (4.8)	7 (36.8)		2 (9.5)		61.0%		55.2%
Others	8 (1.8)	5 (62.5)		3 (37.5)		-		-
Histological grade			< 0.001		0.170		0.001		0.006
G1-G2	200 (46.0)	59 (32.6)		17 (8.5)		57.1%		64.6%
G3	227 (52.2)	119 (65.7)		29 (12.8)		42.8%		52.2%
NR	8 (1.8)	3 (1.7)		2 (25)		83.3%		45.7%
ER			< 0.001		0.098		< 0.001		0.000
No	162 (37.2)	89 (57.8)		23 (14.2)		36.1%		47.1%
Yes	273 (62.8)	92 (35.2)		25 (9.2)		58.2%		64.3%
PgR			0.003		0.246		< 0.001		0.000
No	213 (49)	104 (51.0)		27 (12.7)		41.0%		50.0%
Yes	222 (51)	77 (36.5)		21 (9.5)		58.4%		64.8%
HER2			0.002		0.135		0.334		0.135
No	294 (67.6)	106 (38.3)		28 (9.5)		53.7%		60.4%
Yes	141 (32.4)	75 (54.3)		20 (14.2)		40.8%		52.3%
Molecular subtypes			< 0.001		0.233		< 0.001		< 0.001
Luminal A	107 (24.6)	30 (29.7)		13 (12)		72.0%		76.1%
Luminal B	165 (37.9)	61 (38.4)		12 (7)		50.6%		57.7%
HER2-enriched	77 (17.7)	50 (66.7)		10 (13)		41.5%		54.9%
Triple-Negative	86 (19.8)	40 (50.0)		13 (15)		32.5%		40.3%
Tumor size (cm)			0.183		0.019		0.490		0.250
Median (range)	6.5 (1-24)	6.5 (1-16)		6.0 (2-15)
cT
cT1-cT2	36 (8.3)	19 (54.3)		8 (22.2)		55.0%		69.2%
cT3-cT4	399 (91.7)	162 (42.6)		40 (10)		49.6%		56.8%
cN			0.084		0.743		0.007		0.001
cN0	83 (19.1)	28 (35.0)		10 (12)		65.8%		77.0%
cN1-cN2-cN3	352 (80.9)	153 (45.7)		38 (10.8)		47.2%		54.2%
Clinical stage			0.192		0.088		0.155		0.004
II	72 (16.6)	26 (36.6)		12 (16.7)		62.1%		74.3%
III	363 (83.4)	155 (45.1)		36 (9.9)		48.1%		55.4%
sTIL%					0.002		0.598		0.747
Median (range)	40 (2-95)	70 (60-95)		65 (5-95)
< 50%	266 (61.1)	0 (0)		20 (7.5)		49.6%		55.7%
≥ 50%	149 (34.3)	181 (100)		26 (17.4)		53.9%		63.1%
Missing data	20 (4.6)	20 (0)		2 (10)		-		-
TLCS (d)			0.411		0.633		0.317		0.156
Median (range)	63 (5-982)	58 (8-982)		65 (8-281)
Shorter than median	207 (47.6)	91 (45.5)		22 (10.6)		48.5%		55.0%
Longer than median	211 (48.5)	82 (41.4)		26 (12.3)		56.7%		61.2%
Missing data	17 (3.9)	8 (47.1)		0 (0)		17.6%		46.3%
pCR			0.029				0.002		0.002
No	387 (89)	154 (41.7)		0 (0)		47.4%		55.1%
Yes	48 (11)	27 (58.7)		48 (100)		85.1%		84.9%
Relapse			0.895		< 0.001		< 0.001
No	284 (65.3)	118 (43.4)		42 (14.8)		81.6%		-
Yes	151 (34.7)	63 (44.1)		6 (4)		8.58%		-

TIL: Tumor-infiltrating lymphocytes; pCR: Pathological complete response; OS: Overall survival; DFS: Disease free survival; PgR: Progesterone; TLCS: Time-From-Last-Chemotherapy-To-Surgery.

Table 2 Association between response and Clinical-pathological features regarding molecular subtype n (%)

	Lum A			Lum B			HER2			TN
	Total	pCR	P value	Total	pCR	P value	Total	pCR	P value	Total	pCR	P value
	107	13		165	12		77	10		86	13
Age (yr)			1.000			0.315			0.507			0.157
median (range)	47 (28-75)	46 (28-62)		51 (25-84)	52 (39-69)		51 (28-80)	46 (29-80)		49 (26-73)	45 (28-68)
< 50	72 (67)	9 (13)		78 (48)	4 (5)		37 (48)	6 (16.2)		44 (48)	9 (20)
≥ 50	35 (33)	4 (11)		87 (52)	8 (9)		40 (52)	4 (10)		42 (52)	4 (10)
Histological subtypes			0.349			1.000			0.434			0.392
Ductal	97 (91)	11 (11)		153 (93)	11 (7)		73 (95)	9 (12.3)		83 (97)	12 (14)
Lobular and others	10 (9)	2 (20)		12 (7)	1 (8)		4 (5)	1 (25)		3 (3)	1 (33)
Histological grade			-			0.213			0.266			1.000
G1-G2	103 (97)	12 (12)		61 (39)	2 (3)		23 (30)	1 (4.3)		13 (15)	2 (15)
G3	-	-		102 (61)	10 (10)		53 (69)	9 (17)		72 (85)	10 (14)
NR	4 (3)	1 (25)		2 (1)	0 (0)		1 (1)	0 (0)		1 (0)	1 (100)
Tumor size (cm)			0.102			0.213			0.511			0.620
Median (range)	6 (2-15)	5 (2-9)		7 (2-20)	6 (2-12)		7 (2.5-14)	6 (4-12)		7 (1-24)	8 (3-15)
cT1-cT2	10 (7)	3 (30)		12 (7)	2 (17)		5 (6)	1 (20)		9 (10)	2 (22)
cT3-cT4	97 (93)	10 (10)		153 (93)	10 (7)		72 (94)	9 (12.5)		77 (90)	11 (14)
cN			0.306			0.222			0.270			0.021
cN0	27 (23)	5 (19)		28 (18)	0 (0)		53 (69)	5 (9.4)		14 (14)	4 (29)
cN1-cN2–cN3	80 (77)	8 (10)		137 (82)	12 (9)		24 (31)	5 (20.8)		72 (86)	9 (13)
Clinical stage			0.471			0.652			1.000			0.122
EC II	23 (20)	4 (17)		21 (12)	2 (10)		11 (14)	1 (9.1)		17 (16)	5 (29)
EC III	84 (80)	9 (11)		144 (88)	10 (7)		66 (86)	9 (13.6)		69 (84)	8 (12)
sTIL%			0.054			0.750			0.150			1.000
Median (range)	30 (2-90)	50 (10-90)		40 (5-90)	30 (8-90)		60 (5-95)	80 (30-95)		45 (2-90)	50 (5-80)
< 50	71 (69)	6 (8)		98 (60)	6 (6)		25 (32)	1 (4)		40 (47)	6 (15)
≥ 50	30 (24)	7 (23)		61 (37)	5 (8)		50 (66)	9 (18)		40 (47)	6 (15)
Missing data	6 (6)	0 (0)		6 (3)	1 (17)		2 (3)	0 (0)		6 (7)	1 (17)
TLCS (d)			0.233			0.238			0.744			0.500
Median (range)	67 (14-458)	80 (16-281)		61 (5-412)	54 (8-140)		60 (11-240)	66 (37-106)		64 (8-982)	66 (14-122)
Shorter than median	49 (48)	4 (8)		77 (45)	8 (10)		41 (53)	5 (12.2)		40 (48)	5 (13)
Longer than median	57 (51)	9 (16)		76 (47)	4 (5)		33 (43)	5 (15.2)		45 (51)	8 (18)
Missing data	1 (1)	0 (0)		12 (8)	0 (0)		3 (4)	0 (0)		1 (1)	0 (0)
Relapse			0.121			0.753			0.300			< 0.001
No	87 (79)	13 (15)		109 (65)	9 (8)		46 (60)	8 (17.4)		42 (41)	12 (29)
Yes	20 (21)	0 (0)		56 (35)	3 (5)		31 (40)	2 (6.5)		44 (59)	1 (2)

TIL: Tumor-infiltrating lymphocytes; TLCS: Time-From-Last-Chemotherapy-To-Surgery.

Table 3 Association between percentage of tumor-infiltrating lymphocytes and clinical-pathological features regarding molecular subtype n (%)

	Lum A			Lum B			HER2			TN
	< 50%	≥ 50%	P value	< 50%	≥ 50%	P value	< 50%	≥ 50%	P value	< 50%	≥ 50%	P value
	71	30		98	61		25	50		40	40
Age (yr)			0.181			0.783			0.624			0.074
Median (range)	47 (28-75)	47 (36-74)		52 (28-73)	50 (25-84)		52 (28-66)	49 (29-80)		51 (26-73)	45 (27-73)
< 50	50 (70)	17 (57)		46 (47)	30 (49)		11 (44)	25 (50)		16 (40)	24 (60)
≥ 50	21 (30)	13 (43)		52 (53)	31 (51)		14 (56)	25 (50)		24 (60)	16 (40)
Histological subtypes			0.445			1.000			0.597			1.000
Ductal	66 (93)	26 (87)		91 (93)	57 (93)		23 (92)	48 (96)		39 (98)	38 (95)
Lobular and others	5 (7)	4 (13)		7 (7)	4 (7)		2 (8)	2 (4)		1 (3)	2 (5)
Histological grade			-			0.011			0.514			0.006
G1-G2	69 (97)	28 (93)		43 (44)	15 (25)		9 (36)	14 (28)		11 (28)	2 (5)
G3	0 (0)	0 (0)		53 (54)	46 (75)		16 (64)	35 (71)		29 (73)	38 (95)
NR	2 (3)	2 (7)		2 (2)	0 (0)		0 (0)	1 (2)		0 (0)	0 (0)
Tumor size (cm)
Median (range)	6 (3-13)	6 (2-15)		6 (3-20)	7 (2-15)		7 (3-14)	7 (3-14)		7 (4-24)	7 (1-16)
cT			1.000			0.538			0.659			0.263
cT1-cT2	7 (10)	3 (10)		6 (6)	6 (10)		1 (4)	4 (8)		2 (5)	6 (15)
cT3-cT4	64 (90)	27 (90)		92 (94)	55 (90)		24 (96)	46 (92)		38 (95)	34 (85)
cN			0.890			0.020			0.631			0.762
cN0	18 (25)	8 (27)		22 (22)	5 (8)		6 (24)	8 (16)		6 (15)	7 (18)
cN1-cN2-cN3	53 (75)	22 (73)		76 (78)	56 (92)		11 (44)	27 (54)		34 (85)	33 (83)
Clinical Stage			0.666			0.141			0.742			0.576
EC II	17 (24)	6 (20)		16 (16)	5 (8)		3 (12)	8 (16)		9 (23)	7 (18)
EC III	54 (76)	24 (80)		82 (84)	56 (92)		22 (88)	42 (84)		31 (78)	33 (83)
TLCS (d)			0.631			0.882			0.502			0.141
Median (range)	64 (14-449)	70 (19-458)		61 (5-412)	58 (8-285)		68 (16-234)	56 (11-240)		74 (24-230)	51 (14-982)
Shorter than median	34 (48)	13 (43)		48 (49)	28 (46)		12 (48)	28 (56)		15 (38)	22 (55)
Longer than median	36 (51)	17 (57)		44 (45)	27 (44)		12 (48)	20 (40)		24 (60)	18 (45)
Missing data	1 (1)	0 (0)		6 (6)	6 (10)		1 (4)	2 (4)		1 (3)	0 (0)
pCR			0.054			0.750			0.150			1.000
No	65 (92)	23 (77)		92 (94)	56 (92)		24 (96)	41 (82)		34 (85)	34 (85)
Yes	6 (8)	7 (23)		6 (6)	5 (8)		1 (4)	9 (18)		6 (15)	6 (15)
Relapse			0.450			0.201			0.737			0.502
No	59 (83)	23 (77)		61 (62)	44 (72)		16 (64)	30 (60)		18 (45)	21 (53)
Yes	12 (17)	7 (23)		37 (38)	17 (28)		9 (36)	20 (40)		22 (55)	19 (48)

%sTIL was performed over 415 cases. There 20 missed values. TIL: Tumor-infiltrating lymphocytes; TLCS: Time-From-Last-Chemotherapy-To-Surgery.