Predicting distant dissemination in patients with early breast cancer

Figures & data

Table I.  Patient characteristics and results of the univariate and multivariate analyses for 3 080 patients with known values of histologic tumor size, lymph node status and receptor status. Endpoint is distant metastasis.

				Univariate analysis:		Multivariate analysis:
Factor	Level	Patients (n = 3080)	Events (n = 547)	RH (95% CI)	p-value	RH (95% CI)	p-value
Histologic T size (mm)	≤5	73	2	0.2 (0.1–0.6)		0.2 (0.1–0.9)
	6–10	504	38	0.5 (0.3–0.6)		0.6 (0.4–0.8)
	11–15	781	103	0.8 (0.6–1.0)		0.9 (0.7–1.2)
	16–20	711	117	1.0		1.0
	21–25	463	119	1.8 (1.4–2.3)		1.8 (1.4–2.3)
	26–30	267	70	1.8 (1.3–2.4)		1.5 (1.1–2.0)
	>30	281	98	2.7 (2.1–3.5)	<0.001	2.0 (1.5–2.6)	<0.001
Nodal status	pN0	2118	248	1.0		1.0
	pN1-3	678	166	2.4 (1.9–2.9)		2.1 (1.7–2.6)
	pN4 +	284	133	5.9 (4.7–7.2)	<0.001	4.6 (3.7–5.8)	<0.001
PR (fmol/µg DNA)	<0.05	1584	332	1.0		1.0
	≥0.05	1496	215	0.7 (0.6–0.8)	<0.001	0.8 (0.6–0.9)	0.003
ER (fmol/µg DNA)	<0.05	782	170	1.0		1.0
	≥0.05	2298	377	0.7 (0.6–0.9)	<0.001	0.9 (0.7–1.0)	0.09

RH: relative hazards. CI: confidence interval. PR: progesterone receptors. ER: estrogen receptors.

Table

T size category	Lymph node category	PR category(fmol/µgDNA)
<5mm = 2.5	pN0 = 0	<0.05 = 0
5–10 mm = 7.5	pN1-3 = 1	≥0.05 = 1
11–15 mm = 13	pN4 + = 2
16–20 mm = 18
21–25 mm = 23
26–30 mm = 28
>30 mm = 40

Figure 1a.  Probability of distant metastasis at 10 years according to two metastasis risk scores (MRS) as a continuous variable, including (MRS₁) and excluding progesterone receptors (MRS₂). The other two factors considered were the histologic tumor size and the number of involved axillary lymph nodes. Figure 1b. Probability of distant metastasis at 10 years according to three groups of risk defined by two independent factors: histologic tumor size and number of involved lymph nodes. The metastasis risk groups were defined according to a score below 0.5 (low risk), between 0.5 and 1.5 (intermediate risk) and above 1.5 (high risk).

Table II.  Results of the univariate and multivariate analyses for 4 435 patients with known values of histologic tumor size, and lymph node status. Endpoint is distant metastasis.

				Univariate analysis:		Multivariate analysis:
Factor	Level	Patients (n = 4435)	Events (n = 799)	RH (95% CI)	p-value	RH (95% CI)	p-value
Histologic T size (mm)	≤5	176	6	0.2 (0.1–0.4)		0.2 (0.1–0.6)
	6–10	777	47	0.3 (0.2–0.4)		0.4 (0.3–0.5)
	11–15	1091	155	0.8 (0.6–0.9)		0.8 (0.7–1.0)
	16–20	979	181	1.0		1.0
	21–25	609	156	1.5 (1.3–1.9)		1.5 (1.2–1.9)
	26–30	384	105	1.6 (1.3–2.1)		1.5 (1.2–1.9)
	>30	419	149	2.3 (1.9–2.9)	<0.001	1.8 (1.4–2.2)	<0.001
Nodal status	pN0	3114	364	1.0		1.0
	pN1-3	926	245	2.6 (2.2–3.0)		2.2 (1.8–2.5)
	pN4 +	395	190	6.1 (5.1–7.2)	<0.001	4.5 (3.7–5.4)	<0.001

RH: relative hazards. CI: confidence interval.

Table III.  Ten-year cumulative incidence rates (first cause of failure and total events ) according to risk of distant dissemination in 4 435 patients with known values of histologic tumor size and lymph node status.

	FIRST CAUSE OF FAILURE					TOTAL EVENTS
Event	LR (%)	IR (%)	RR1	HR (%)	RR2	P1	LR (%)	IR (%)	RR1	HR (%)	RR2	P2
Local recurrence	9.3	10.2	1.30	14.7	2.71	<0.0001	11.6	13.5	1.24	25.6	2.76	<0.0001
Distant metastasis	7.4	18.1	2.71	37.5	8.91	<0.0001	11.6	25.8	2.47	54.4	7.73	<0.0001
CBC	7.5	5.0	0.86	4.8	1.17	0.33	9.3	6.6	0.85	11.2	1.32	<0.06
NPM	6.2	6.3	1.25	6.0	2.00	0.005	7.8	9.2	1.23	9.4	1.63	0.047
Intercurrent death	7.6	10.1	1.65	10.0	2.53	<0.0001	–	–	–	–	–	–
Any first event (1)	37.9	49.7	1.57	73.0	3.57	<0.0001	–	–	–	–	–	–

LR: low risk group (1 656 patients). IR: intermediate risk group (2 011 patients). HR: high risk group (768 patients).

RR: relative risk compared to the low risk group defined as 1. RR1 compared IR to LR and RR2 compared HR to LR.

P1: Gray test. P2: log-rank test.

CBC: contralateral breast cancer. NPM: new primary malignancy.

(1) complementary value of event-free survival. Not applicable for total events.

Figure 2.  Probability of distant metastasis at 10 years according to the histologic tumor size and the number of involved axillary lymph nodes. Lines represent the estimations obtained by a Cox model for the effect on each category and marks are the observed values for pN0 (o), pN1-3 (+) and pN4+ (Δ).

Figure 3a.  Probability of distant metastasis for the Stockholm database – unfilled marks-compared with the IGR published data (12) – black marks – according to tumor size and lymph node involvement. Figure 3b. Overall results of 10-year distant metastasis rate for the Stockholm material –triangles – according to histological observed values of tumor size and for the IGR published data (12) – squares according to clinical tumor size. The linear fitting for the Stockholm series is r²=0.96, and for the IGR series r²=0.99; both highly significant (p < 0.0001). The numbers of patients in each group are given at the bottom.