Diverse Distribution and Gene Expression on the 21-Gene Recurrence Assay in Breast Cancer Patients with Locoregional Recurrence Versus Distant Metastasis

Figures & data

Table 1 Baseline characteristics of study participants and impact factors for recurrence status

	Total (n)	No recurrence, n (%)	LRR, n (%)	DM, n (%)	P
	1,287	n=1,213	n=27	n=47
Age (years), median (range)	58.0 (24–92)	58.0 (27–92)	59.0 (24–87)	53.0 (30–82)	0.495
<50 years	390	365 (93.59)	7 (1.79)	18 (4.62)
50–65 years	551	519 (94.19)	11 (2.00)	21 (3.81)
≥65 years	346	329 (95.09)	9 (2.60)	8 (2.31)
Menstrual status
Premenopausal	462	434 (93.94)	9 (1.95)	19 (4.11)	0.778
Postmenopausal	825	779 (94.42)	18 (2.18)	28 (3.39)
BMI
<24	720	683 (94.86)	12 (1.67)	25 (3.47)	0.851
≥24	483	455 (94.20)	10 (2.07)	18 (3.73)
NA	84	75 (89.29)	5 (5.95)	4 (4.76)
Number of lesions
Unifocal	1,196	1,127 (94.23)	25 (2.09)	44 (3.68)	0.981
Multifocal	91	86 (94.51)	2 (2.20)	3 (3.30)
Histological type
IDC	1126	1060 (94.14)	24 (2.13)	42 (3.73)	0.900
Others	161	153 (95.03)	3 (1.86)	5 (3.11)
Histological grade
1	206	198 (96.12)	3 (1.46)	5 (2.43)	0.481
2	766	724 (94.52)	15 (1.96)	27 (3.52)
3	315	291 (92.38)	9 (2.86)	15 (4.76)
pT stage
1	903	864 (95.68)	15 (1.66)	24 (2.66)	0.003
2	384	349 (90.89)	12 (3.13)	23 (5.99)
pN stage
0	1,092	1,035 (94.78)	23 (2.11)	34 (3.11)	0.051
1	195	178 (91.28)	4 (2.05)	13 (6.67)
ER
Negative	6	6 (100)	0	0	0.832
Positive	1,281	1,207 (94.22)	27 (2.11)	47 (3.67)
PR
Negative	179	163 (91.06)	8 (4.47)	8 (4.47)	0.046
Positive	1,108	1,050 (94.77)	19 (1.71)	39 (3.52)
Ki67
<14%	656	632 (96.34)	9 (1.37)	15 (2.29)	0.004
≥14%	631	581 (92.08)	18 (2.85)	32 (5.07)
LVI
Yes	41	39 (95.12)	0	2 (4.88)	0.587
No	1,246	1174 (94.22)	27 (2.17)	45 (3.61)
21-gene RS
<18	361	357 (98.89)	1 (0.28)	3 (0.83)	<0.001
18–30	685	657 (95.91)	7 (1.02)	21 (3.07)
≥31	241	199 (82.57)	19 (7.88)	23 (9.54)

Note: Bold values indicate significant differences.

Abbreviations: LRR, locoregional recurrence; DM, distant metastasis; BMI, body-mass index; NA, not available; BCS, breast-conserving surgery; IDC, invasive ductal carcinoma; ER, estrogen receptor; PR, progestogen receptor; LVI, lymphovascular invasion.

Figure 1 Flowchart of included patients.

Abbreviations: CBHC, Comprehensive Breast Health Center; RS, recurrence score; IHC, immunohistochemical.

Table 2 Multivariate analysis of impact factors for recurrence status

	LRR			DM			P
	OR	95% CI	P	OR	95% CI	P
pT stage
1	0.63	0.29–1.39	0.254	0.50	0.28–0.91	0.023	0.049
2	1.00			1.00
Ki67
<14%	0.68	0.30–1.57	0.367	0.58	0.30–1.09	0.090	0.160
≥14%	1.00			1.00
PR
Negative	1.72	0.72–4.13	0.224	0.96	0.43–2.14	0.925	0.492
Positive	1.00			1.00
21-gene RS
<18	0.04	0.01–0.27	0.001	0.09	0.03–0.29	<0.001	<0.001
18–30	0.13	0.05–0.32	<0.001	0.31	0.17–0.58	<0.001
≥31	1.00			1.00

Notes: Reference category, no recurrence. Bold values indicate significant differences.

Abbreviations: LRR, locoregional recurrence; DM, distant metastasis; RS, recurrence score.

Table 3 Local and systemic treatment based on recurrence status

	Total (n)	No recurrence, n (%)	LRR, n (%)	DM, n (%)	P
	1,287	n=1213	n=27	n=47
Breast surgery
Mastectomy	761	716 (94.09)	17 (2.23)	28 (3.68)	0.917
BCS	526	497 (94.49)	10 (1.90)	19 (3.61)
Axillary surgery
SLNB	788	754 (95.69)	13 (1.65)	21 (2.66)	0.020
ALND	499	459 (91.98)	14 (2.81)	26 (5.21)
Radiation therapy
Yes	565	535 (94.69)	8 (1.42)	22 (3.89)	0.299
No	722	678 (93.91)	19 (2.63)	25 (3.46)
Chemotherapy
Yes	647	600 (92.74)	14 (2.16)	33 (5.10)	0.020
No	640	613 (95.78)	13 (2.03)	14 (2.19)
Endocrine therapy
Yes	1242	1172 (94.36)	25 (2.01)	45 (3.62)	0.508
No	45	41 (91.11)	2 (4.44)	2 (4.44)

Note: Bold values indicate significant differences.

Abbreviations: LRR, locoregional recurrence; DM, distant metastasis; BCS, breast-conserving surgery; SLNB, sentinel lymph–node biopsy; ALND, axillary lymph node–dissection.

Figure 2 Distribution of 21-gene RS (A) and RS category (B) by recurrence status. ***P<0.001.

Abbreviations: RS, recurrence score; LRR, locoregional recurrence; DM, distant metastasis; NS, notsignificant.

Figure 3 Distribution of 21-gene RS according to recurrence status stratified by (A) tumor size, (B) node status (C), adjuvant chemotherapy, and (D) adjuvant radiation therapy. *P<0.05; **P<0.01; ***P<0.001.

Abbreviations: DM, distant metastasis; LRR, locoregional recurrence; CT, chemotherapy; RT, radiation therapy; NS, notsignificant.

Figure 4 Distribution of single-gene expression in breast cancer patients with LRR, DM, and no recurrence in the proliferation group (A), invasive group (B), HER2 group (C), ER group (D), CD68 (E), GSTM1 (F), and BAG1 (G). *P<0.05; **P<0.01; ***P<0.001.

Abbreviations: LRR, locoregional recurrence; DM, distant metastasis; NS, notsignificant.