Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013

Figures & data

Figure 1. Cohort flow diagram.

Table 1. Patient and tumor characteristics.

	Patient material I	Patient material II	Patient material III	Total
	SB22-pre	SB22-post	BMM	I + II + III
Factor	N (%)	N (%)	N (%)	N (%)
Number of patients	185	103	273	561
Age
Median, years	46	65	58	54
Range, years	36–56	43–81	37–88	36–88
Menopausal status
Premenopausal	185 (100)	0	47 (17)	232 (41)
Postmenopausal	0	103 (100)	225 (83)	328 (59)
Unknown	0	0	1	1
Tumor size
T1	79 (43)	37 (36)	206 (75)	322 (57)
T2	106 (57)	66 (64)	67 (25)	239 (43)
Median, mm	22	22	15	20
Range, mm	2–50	2–50	1–45	1–50
‘Luminal A-like’	151 (82)	65 (63)	174 (64)	390 (70)
‘Luminal B-like (HER2-neg)’	34 (18)	38 (37)	99 (36)	171 (30)
Lymph nodes
Negative	63 (34)	36 (35)	193 (71)	292 (52)
1 Positive	56 (30)	36 (35)	50 (18)	142 (25)
2 Positive	40 (22)	19 (18)	21 (8)	80 (14)
3 Positive	26 (14)	12 (12)	9 (3)	47 (8)
ER status
Positive	185 (100)	103 (100)	273 (100)	561 (100)
PgR status
Negative	10 (5)	30 (29)	58 (21)	98 (17)
Positive	175 (95)	73 (71)	215 (79)	463 (83)
Histological grade
G1	35 (19)	6 (6)	84 (31)	125 (22)
G2	104 (56)	85 (83)	156 (57)	345 (62)
G3	46 (25)	12 (12)	33 (12)	91 (16)
Ki-67
Low	160 (86)	88 (85)	217 (79)	465 (83)
High	25 (14)	15 (15)	56 (21)	96 (17)
HER-2 status
Negative	185 (100)	103 (100)	273 (100)	561 (100)
Adjuvant treatment
Endocrine therapy	88 (48)	103 (100)	181^a (66)	372^a (66)
Chemotherapy	0	0	9^a (3)	9^a (2)
None	97 (52)	0 (0)	89 (33)	186 (33)
DDFS 10 years
Number of patients^b	125 (68)	76 (74)	236 (86)	437 (78)
Median, years	10	5.7	8.9	9.3
Range, years	10–10	2.5–10	6.2–10	2.5–10

^aSix patients received endo-chemotherapy; ^bNumber of patients alive without metastasis at last follow-up (truncated at 10 years).

Figure 2. Distant disease-free survival (DDFS) by St Gallen subtypes, ‘Luminal A-like’ and ‘Luminal B-like (HER2-negative)’, for all patients (a) and for patients treated with adjuvant endocrine therapy alone (b).

Figure 3. Distant disease-free survival (DDFS) by histological grade (G) and St Gallen subtypes, ‘Luminal A-like’ and ‘Luminal B-like (HER2-negative)’, for all patients (a) and for patients treated with adjuvant endocrine therapy alone (b).

Table 2. Patient and tumor characteristics of ‘luminal A-like’ versus ‘luminal B-like (HER2-negative)’.

	‘Luminal A-like’	‘Luminal B-like (HER2-neg)’
Factor	N (%)	N (%)
Number of patients	390	171
Material I SB22-pre	151 (38)	34 (20)
Material II SB22-post	65 (17)	38 (22)
Material III BMM	174 (45)	99 (58)
Age
Median, years	53	58
Range, years	36–88	37–86
Menopausal status
Premenopausal	182 (47)	50 (29)
Postmenopausal	208 (53)	120 (71)
Unknown	0	1
Tumor size
Median, mm	19	20
Range, mm	1–50	2–45
Lymph nodes
Negative	189 (48)	103 (60)
1 Positive	103 (26)	39 (23)
2 Positive	65 (17)	15 (9)
3 Positive	33 (8)	14 (8)
PgR status
Negative	0 (0)	98 (57)
Positive	390 (100)	73 (43)
Histological grade
G1	102 (26)	23 (13)
G2	248 (64)	97 (57)
G3	40 (10)	51 (30)
Ki-67
Low	390 (100)	75 (44)
High	0 (0)	96 (56)
Adjuvant endocrine therapy
Yes	247 (63)	125 (73)
No	143 (37)	46 (27)
Adjuvant chemotherapy
Yes	4 (1)	5 (3)
No	386 (99)	166 (97)
Adjuvant chemo and/or endocrine therapy
Yes	248 (64)	127 (74)
No	142 (36)	44 (26)
Events, <10 years follow-up
Alive, no metastasis	307	130
Distant metastasis	69	34

Table 3. Multivariable analysis of all patients (N = 561; stratified for patient material).

Factor	Hazard ratio	95% Confidence interval	p-Value
Grade 2 vs. 1	2.8	1.3–6.0	.006
Grade 3 vs. 1	4.4	2.0–11	<.001
‘Luminal A-like’ vs.
‘Luminal B-like’	1.2	0.77–1.9	.40
T2 vs. T1	1.3	0.85–2.0	.22
N1 vs. N0	1.6	1.03–2.5	.036
Age (cont.)	1.0	0.99–1.05	.23

Table 4. Multivariable analysis of patients treated with endocrine therapy (N = 372; stratified for patient material).

Factor	Hazard ratio	95% Confidence interval	p-Value
Grade 2 vs. 1	5.3	1.3–22	.023
Grade 3 vs. 1	9.6	2.2–42	.003
‘Luminal A-like’ vs.
‘Luminal B-like’	1.2	0.72–2.1	.45
T2 vs. T1	1.7	0.97–2.8	.066
N1 vs. N0	2.0	1.2–3.5	.009
Age (cont.)	1.0	0.99–1.06	.10

Figure 4. Distant disease-free survival (DDFS) in ER-positive/HER2-negative, G2 breast cancer stratified by PgR (negative vs. positive; a), DDFS in G2 tumors stratified by Ki-67 (high vs. low; b).