ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy

Figures & data

Figure 1 Flow diagram of patient recruitment.

Abbreviations: AIs, aromatase inhibitors; ER, estrogen receptor; TAM, tamoxifen.

Figure 2 Immunohistochemical staining for Ki-67 expression in breast cancer.

Notes: (A) Ki-67 low expression (<14%), (B) Ki-67 high expression (≥14%). Original magnification ×200.

Table 1 Summary of patients’ clinicopathologic characteristics and the associations with RFS and DMFS for all patients

Characteristics	No of patients (%)	RFS		DMFS
		Log-rank χ^2	P-value	Log-rank χ^2	P-value
All patients	327
Age (years)		0.019	0.892	0.096	0.757
≤50	141 (43.1)
>50	186 (56.9)
Menopausal status		0.609	0.435	0.083	0.773
Premenopausal	129 (39.4)
Postmenopausal	198 (60.6)
Tumor size (cm)		0.078	0.780	1.039	0.308
≤2.0	173 (52.9)
>2.0	154 (47.1)
Number of LNM		11.819	0.003	12.995	0.002
0	196 (59.9)
1–3	83 (25.4)
≥4	48 (14.7)
Pathologic type		1.179	0.278	0.731	0.393
IDC	270 (82.6)
Non-IDC	57 (17.4)
Histologic grade		16.290	0.000	12.539	0.000
1/2	241 (73.7)
3	80 (24.5)
Unclear	6 (1.8)
TNM stage		7.537	0.023	9.234	0.010
I	122 (37.3)
II	151 (46.2)
III	54 (16.5)
HER2		0.010	0.922	0.286	0.593
Negative or 1+	241 (73.7)
2+ or 3+	86 (26.3)
Chemotherapy		0.108	0.742	0.028	0.868
Yes	285 (87.2)
No	42 (12.8)
Radiation therapy		4.472	0.034	8.437	0.004
Yes	105 (32.1)
No	222 (67.9)
Endocrine therapy		0.397	0.529	1.002	0.317
TAM	261 (79.8)
AIs	66 (20.2)
Ki-67		7.134	0.008	4.594	0.032
High	168 (51.4)
Low	159 (48.6)
PR		0.559	0.342	0.298	0.585
+	276 (84.4)
−	51 (15.6)

Notes: TNM stage is according to AJCC stage, 7th edition. Bold values show statistical significance (P<0.05).

Abbreviations: AIs, aromatase inhibitors; AJCC, American Joint Committee on Cancer; DMFS, distant metastasis-free survival; IDC, invasive ductal carcinoma; LNM, lymph node metastasis; PR, progesterone receptor; RFS, recurrence-free survival; TAM, tamoxifen.

Figure 3 Kaplan–Meier plot of recurrence-free survival according to (A) histologic grade, P=0.000; (B) Ki-67, P=0.003 and (C) number of positive nodes, P=0.008.

Figure 4 Kaplan–Meier plot of distant metastasis-free survival according to (A) histologic grade, P=0.000; (B) Ki-67, P=0.002 and (C) number of positive nodes, P=0.032.

Table 2 Univariate analysis for RFS and DMFS in ER+ breast cancer

Factors	RFS			DMFS
	HR	95% CI of HR	P-value	HR	95% CI of HR	P-value
Radiation therapy	1.624	1.030–2.562	0.037	2.384	1.301–4.371	0.005
Histologic grade	2.480	1.568–3.922	0.000	2.856	1.553–5.250	0.001
Ki-67	1.873	1.170–2.996	0.009	1.987	1.046–3.775	0.036
Node status			0.004			0.003
1–3 vs 0	1.474	0.853–2.548	0.164	2.088	1.004–4.343	0.049
>3 vs 0	2.524	1.461–4.362	0.001	3.535	1.700–7.351	0.001
TNM			0.028			0.014
II vs I	1.073	0.631–1.826	0.794	1.329	0.622–2.839	0.463
III vs I	2.062	1.154–3.683	0.015	2.999	1.361–6.607	0.006
Age	1.032	0.654–1.627	0.892	0.909	0.495–1.669	0.757
Menopausal status	1.203	0.754–1.918	0.438	0.914	0.496–1.685	0.773
Tumor size	1.066	0.680–1.671	0.781	1.369	0.746–2.514	0.311
Pathologic type	0.960	0.667–1.382	0.825	0.667	0.350–1.270	0.218
HER2	0.974	0.579–1.639	0.922	1.201	0.613–2.351	0.594
Chemotherapy	1.123	0.560–2.253	0.743	1.083	0.425–2.755	0.868
Endocrine therapy	1.188	0.693–2.038	0.531	0.646	0.272–1.533	0.322
PR	0.842	0.471–1.504	0.561	0.807	0.374–1.745	0.587

Note: Bold values show statistical significance (P<0.05).

Abbreviations: DMFS, distant metastasis-free survival; ER, estrogen receptor; HR, hazard ratio; PR, progesterone receptor; RFS, recurrence-free survival.

Table 3 Multivariable analyses of RFS and DMFS in ER+ breast cancer

Factors	RFS			DMFS
	HR	95% CI of HR	P-value	HR	95% CI of HR	P-value
Radiation therapy	1.064	0.589–1.922	0.837	1.491	0.697–3.192	0.303
Histologic grade	2.098	1.300–3.385	0.002	2.212	1.166–4.194	0.015
Ki-67	1.477	0.902–2.417	0.121	1.420	0.723–2.791	0.309
Node status			0.091			0.222
1–3 vs 0	1.170	0.659–2.078	0.591	1.522	0.702–3.300	0.287
>3 vs 0	2.176	1.071–4.421	0.032	2.245	0.894–5.637	0.085
TNM			0.290			0.494
II vs I	0.839	0.485–1.450	0.529	0.981	0.447–2.154	0.963
III vs I	1.379	0.693–2.745	0.360	1.553	0.612–3.940	0.355

Note: Bold values show statistical significance (P<0.05).

Abbreviations: DMFS, distant metastasis-free survival; ER, estrogen receptor; HR, hazard ratio; RFS, recurrence-free survival.