Robust and validated models to predict high risk of non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node

Figures & data

Table I. Patient, tumor and sentinel node characteristics according to risk of NSN metastases in 181 Danish breast cancer patients with ITC and 739 patients with micrometastases in the SN operated between 2009 and 2010.

Variables	Isolated tumor cells				Micrometastases
	NSN metastases			p-value	NSN metastases			p-value
	No	Yes	%		No	Yes	%
Total	158	23	12.7		614	125	16.9
Age, years				0.49				0.53
< 40	3	0	0		23	1	4.2
40–49	19	5	20.8		88	19	17.8
50–59	58	8	12.1		200	44	18.0
60–69	66	7	9.6		232	48	17.1
≥ 70	12	3	20.0		71	13	15.5
Tumor size, cm				0.32				0.0005
≤ 1	32	2	5.9		126	9	6.7
> 1–≤ 2	72	9	11.1		315	64	16.9
> 2–≤ 3	36	8	18.2		130	38	22.6
> 3	17	4	19.0		43	14	25.0
Unknown	1	0	0
WHO type				0.86				0.63
Ductal	93	15	13.9		527	109	17.1
Lobular	48	6	11.1		52	8	13.3
Other	16	2	11.1		31	8	20.5
Unknown	1	0	0		4	0	0
Grade				0.04				0.01
Grade I	38	6	13.6		207	27	11.5
Grade II	73	7	8.8		236	64	21.3
Grade III	21	8	27.6		94	22	19.0
Unknown/other	26	2	7.1		77	12	13.5
LVI				0.63				0.0007
Present	9	2	18.2		68	28	29.2
Absent	148	21	12.4		537	96	15.2
Unknown	1	0	0		9	1	10.0
Hormone receptor status				0.47				0.68
Positive	138	22	13.8		556	111	16.6
Negative	18	1	5.3		57	13	18.6
Unknown	2	0	0		1	1	50.0
HER2 status				0.51				0.13
Positive	19	4	17.4		68	19	21.8
Negative	127	18	12.4		511	93	15.4
Unknown	12	1	7.7		35	13	27.1
Location of tumor in breast				0.77				0.03
Upper lateral	83	13	13.5		337	81	19.4
Not upper lateral	73	10	12.0		273	42	13.3
Unknown	2	0	0		4	2	33.3
No. removed SN				0.36				0.20
1	48	11	18.6		212	54	20.3
2	64	6	8.6		224	32	12.5
3	22	4	15.4		110	24	17.9
4	18	1	5.3		48	10	17.2
5	6	1	14.3		20	5	20.0
Positive SN/ Removed SN				0.22				0.33
100%	58	13	18.3		248	58	19.0
> 33% , < 100%	70	6	7.9		220	34	13.4
> 25; ≤ 33	16	3	15.8		89	20	18.3
≤ 25%	14	1	6.7		57	13	18.6

ITC, isolated tumor cells; LVI, lymphovascular invasion; NSN, non-sentinel nodes; SN, sentinel node.

Table II. Multivariate analyses of patients and tumor characteristics according to non-sentinel node metastases in Danish breast cancer patients with ITCs or micrometastases in the sentinel node.

	Original cohort 2002–2008			Validation cohort 2009–2010
	Isolated tumor cells
	n = 299			n = 180
	OR	95% CI	p-value	OR	95% CI	p-value
Tumor size, > 2 vs. ≤ 2 cm	4.21	1.74–10.2	0.001	2.04	0.84–4.96	0.12
Age at diagnosis, < 40 vs. ≥ 40 years	3.57	1.11–11.4	0.03	–	–	–
Proportion of pos SN, 100% vs. < 100%	2.90	1.27–6.60	0.01	2.12	0.87–5.17	0.10
	Micrometastases
	n = 1521			n = 720
Tumor size, cm, Trend	1.22	1.06–1.39	0.005	1.34	1.12–1.60	0.002
Proportion of pos SN, 100% vs. < 100%	1.69	1.29–2.21	0.0001	1.32	0.88–1.97	0.18
Lymphovascular invasion	1.74	1.18–2.55	0.005	2.26	1.37–3.74	0.001
HR status, neg vs. pos	1.47	1.00–2.16	0.049	1.06	0.55–2.03	0.86
Location of tumor in upper lateral quadrant	1.72	1.30–2.26	0.0003	1.47	0.97–2.23	0.07

CI, confidence interval; HR, hormone receptor; neg, negative; OR, odds ratio; pos, positive; SN, sentinel node.

Table III. Performance of models predicting non-sentinel node metastases in original and validation cohorts of Danish breast cancer patients with ITCs or micrometastases in the sentinel node.

Model	Cohort	Operation year	No. of patients	Sensitivity	Specificity	AUC (95%CI)
ITC	Original cohort	2002–2008	299	0.43*	0.85*	0.73 (0.64–0.82)
	Validation cohort	2009–2010	180	0.48*	0.88*	0.60 (0.46–0.75)
MIC	Original cohort	2002–2008	1521	0.25‡	0.88‡	0.64 (0.60–0.67)
	Validation cohort	2009–2010	720	0.36‡	0.81‡	0.63 (0.57–0.68)

ITC, isolated tumor cells; MIC, micrometastases.

*For cut-point of more than one risk factor present; ‡For cut-point of 30% observed risk of non-sentinel node metastases.