Failure pattern and survival after breast conserving therapy. Long-term results of the Danish Breast Cancer Group (DBCG) 89 TM cohort

Figures & data

Figure 1. Patients included, excluded, and allocated into risk groups and treatment. Patients to be included in the cohort, treated according to the DBCG 89 program and identified through the DBCG database (n = 1962). Patients excluded from the cohort (n = 115). Patients left for analyses (n = 1847) separated into low- and high-risk groups and further into treatment sub-groups.

Table 1. Patient, tumor and treatment characteristics in the cohort and in age groups.

	All		≤45 years		46–55 years		≥56 years
Variable	N	%	N	%	N	%	N	%
	1847	100	947	51	470	26	430	23
Age at diagnosis (years)
Median (range)	46 (22–70)
Follow-up time (years)
Median (range)	17 (0.4–25)		17 (0.5–25)		18 (0.7–25)		16 (0.4–25)
Menopausal status
Pre	1145	62	930	98	212	45	3	1
Post	702	38	17	2	258	55	427	99
Tumor diameter (mm)
0–10	418	23	223	24	92	20	103	24
11–20	971	53	495	52	264	56	212	49
21–30	349	19	169	18	92	20	88	21
31–50	83	4	38	4	20	4	25	6
>50	4	<1	4	<1	0	0	0	0
</= 50 mm#	22	1	18	2	2	<1	2	<1
Median (range)	15 (1–70)		15 (1–70)		15 (1–50)		17 (2–50)
Tumor type
Ductal, gr I	597	32	300	32	158	33	169	32
Ductal, gr II–III	963	52	516	54	239	51	208	49
Ductal, gr unknown	36	2	16	2	12	3	8	2
Lobular	124	7	49	5	32	7	43	10
Medullary	67	4	40	4	13	3	14	3
Other*	60	3	26	3	16	3	18	4
ER status
Positive	1062	57	516	55	267	57	279	65
Negative	453	25	277	29	105	22	71	17
Unknown	332	18	154	16	98	21	80	19
No. of LN removed
Median (range)	12 (2–37)		12 (1–36)		12 (3–35)		12 (2–40)
Nodal status
Negative	1228	67	620	65	314	67	294	69
1–3 pos	488	26	265	28	127	27	96	22
4+ pos	131	7	62	7	29	6	40	9
Median (range)	0 (0–31)		0 (0–31)		0 (0–17)		0 (0–15)
Adjuvant treatment
None	929	50	373	39	269	57	287	67
CMF	459	25	354	37	84	18	21	5
Ovarian ablation	122	7	89	10	33	7	0	0
CEF	121	6	100	11	17	4	4	1
Tamoxifen or Tam + Femar	179	10	5	1	61	13	113	26
CMF + Pamidronat	22	1	13	1	4	1	5	1
CEF + Pamidronat	15	1	13	1	2	<1	0	0
First failure
No event	821	44	413	44	255	54	153	36
LRR – all local failures	277	15	177	19	49	10	51	12
RRiso	47	3	30	3	6	1	11	3
DMiso	387	21	201	21	87	18	100	23
CCiso	99	5	53	6	27	6	21	5
Other malignancy	144	8	55	6	39	2	50	10
Death (as first failure)	72	4	18	2	10	8	44	12
Vital status
Alive	1206	65	631	66	351	75	224	52
Dead	641	35	316	34	119	25	206	48
Death cause
Breast cancer	474	74	266	84	86	72	122	59
Other malignancy	78	12	27	9	19	16	32	16
Non-malignant causes	89	14	23	7	14	12	52	25

Patient, tumor and treatment characteristics in the entire cohort and in age groups. * Unknown histological type in 3 cases, # the only information on tumor size was “<50 mm” in 22 cases.

Figure 2. Cumulative incidences of first failures and survival endpoints for the entire cohort. A: Cumulative incidences of first failures at 20 years for the entire cohort, calculated in a competing risks model. B: Cumulative overall and recurrence-free survival at 20 years for the entire cohort.

Table 2. Uni- and multivariate analyses of LR and DSM.

	Local recurrence						Disease-specific mortality
		Univariate			Multivariate			Univariate			Multivariate
	HR	CI	P	HR	CI	P	HR	CI	P	HR	CI	P
Menopausal status
Post	1.0			1.0			1.0			1.0
Pre	1.6	1.2–2.1	<0.01	2.1	1.5–3.0	<0.01	1.0	0.8–1.2	1.0	1.1	0.9–1.5	0.4
Tumor diameter (mm)
0–10	1.0			1.0			1.0			1.0
11–20	1.1	0.8–1.5	0.5	1.1	0.8–1.5	0.4	2.3	1.7–3.1	<0.01	1.9	1.4–2.6	<0.01
21–30	1.0	0.6–1.4	0.8	0.9	0.6–1.4	0.7	3.3	2.4–4.6	<0.01	2.2	1.6–3.2	<0.01
31–50	2.0	1.2–3.4	0.01	2.2	1.2–4.0	<0.01	3.6	2.3–5.6	<0.01	2.4	1.5–3.8	<0.01
>50*	–	–	–	–	–	–	4.3	1.0–17.5	0.04	–	–	–
</= 50 mm*	1.8	0.7–4.4	0.2	–	–	–	1.9	0.8–4.7	0.2	–	–	–
Tumor type
Ductal, gr I	1.0			1.0			1.0			1.0
Ductal, gr II–III	1.1	0.9–1.5	0.4	1.4	1.0–2.0	0.07	2.4	1.8–3.0	<0.01	1.8	1.4–2.4	<0.01
Ductal, gr unknown*	1.4	0.7–3.1	0.4	–	–	–	1.3	0.6–2.9	0.5	–	–	–
Lobular	1.3	0.8–2.2	0.2	1.5	0.9–2.4	0.1	1.8	1.2–2.7	<0.01	1.5	1.0–2.3	0.04
Medullary	1.0	0.5–2.0	0.9	1.0	0.5–2.1	1.0	1.4	0.8–2.5	0.3	1.0	0.5–1.8	0.9
Other*	1.1	0.5–2.2	0.8	1.3	0.6–2.5	0.5	1.2	0.6–2.3	0.6	1.1	0.6–2.2	0.7
ER status
Positive	1.0			1.0			1.0			1.0
Negative	0.9	0.7–1.2	0.5	0.8	0.6–1.1	0.2	1.4	1.1–1.7	<0.01	1.3	1.0–1.7	0.03
Unknown	0.9	0.6–1.2	0.3	0.8	0.6–1.1	0.2	0.8	0.6–1.0	0.04	0.8	0.6–1.0	0.1
Nodal status
Negative	1.0			1.0			1.0			1.0
1–3 pos	1.2	0.9–1.5	0.3	1.6	1.0–2.5	0.05	2.0	1.6–2.4	<0.01	1.9	1.4–2.7	<0.01
4+ pos	1.3	0.7–2.1	0.4	2.0	1.0–3.7	0.04	4.9	3.8–6.3	<0.01	4.5	3.1–6.5	<0.01
Adjuvant treatment
None	1.0			1.0			1.0			1.0
CMF	1.1	0.8–1.5	0.4	0.6	0.4–0.9	0.02	2.1	1.7–2.7	<0.01	0.8	0.6–1.2	0.2
Ovarian ablation	0.8	0.4–1.4	0.4	0.3	0.1–0.6	<0.01	2.1	1.5–2.9	<0.01	0.6	0.4–1.1	0.08
CEF	1.1	0.6–1.7	0.8	0.6	0.3–1.1	0.1	1.4	0.9–2.1	0.09	0.6	0.3–0.9	0.02
Tamoxifen or Tam + Femar	0.9	0.6–1.4	0.6	0.7	0.4–1.4	0.3	2.4	1.8–3.2	<0.01	0.9	0.5–1.3	0.5
CMF + Pamidronat*	2.3	1.0–5.2	0.05	–	–	–	2.8	1.4-5.4	<0.01	–	–	–
CEF + Pamidronat*	1.3	0.4–4.0	0.7	–	–	–	1.6	0.6-4.2	0.4	–	–	–
Age groups
Middle-age (46–55 y)	1.0			1.0			1.0			1.0
young (≤45 y)	2.1	1.5–2.9	<0.01	1.8	1.2–2.7	<0.01	1.6	1.3–2.1	<0.01	1.9	1.4–2.7	<0.01
Old (≥56 y)	1.5	1.0–2.2	0.06	1.7	1.1–2.8	0.03	1.7	1.3–2.3	<0.01	1.8	1.3–2.5	<0.01

The associations between patient-, tumor- and treatment-related variables and either LR or disease-specific mortality expressed as hazard ratios. *Sub-groups with very few patients are omitted from the multivariate analyses.

Figure 3. A: Hazard ratios for disease-specific mortality calculated in 5-year age intervals. B: Cumulative incidence of LR at 20 years in young, middle-aged and older patients. C: Cumulative incidence of distant metastases at 20 years in young, middle-aged and older patients. D: Cumulative overall survival at 20 years in young, middle-aged and older patients. E: Cumulative recurrence-free survival in young, middle-aged and older patients. F: Cumulative disease-specific mortality in young, middle-aged and older patients.

Table 3. Cumulative incidence proportions and HR of first failures and survival endpoints for the entire cohort and between age groups.

	10-year		20-year		</=45 year		46–55 year		>/=56 year
	%	CI	%	CI	%	HR (CI)	%	HR	%	HR (CI)
LR(all)	9.9	8.6–11.3	15.3	13.6–17.0	18.9	2.1 (1.5–2.9)	10.5	1	12.4	1.5 (1.0–2.2)
LRiso	8.0	6.8–9.3	12.7	11.2–14.4	16.4	2.4 (1.6–3.4)	8.1	1	9.8	1.4 (0.9–2.3)
RRiso	2.3	1.7–3.0	2.6	1.9–3.4	–	–	–	–	–	–
DMiso	17.3	15.6–19.1	21.1	19.3–23.0	21.5	1.3 (1.0–1.7)	17.9	1	23.2	1.5 (1.1–2.0)
CCiso	3.3	2.6–4.2	5.6	4.6–6.8	–	–	–	–	–	–
DSM	18.2	16.5–20.0	26.3	24.2–28.3	28.9	1.6 1.3–2.1)	18.9	1	28.4	1.7 (1.3–2.3)
OS,10y	78.6	76.6–80.3	–	–	78.0	1.7 (1.3–2.5)	86.4	1	71.3	2.3 (1.7–3.0)
OS,20y	–	–	63.7	61.2–66.0	65.5	1.4 (1.1–1.7)	73.4	1	48.8	2.2 (1.7–2.7)
RFS	62.4	60.2–64.1	43.0	40.6–45.5	42.3	1.4 (1.2–1.7)	53.4	1	32.9	1.7 (1.4–2.0)

Cumulative incidence proportions at 10 and 20 years for chosen endpoints for the entire cohort and in age sub-groups. Hazard ratios (HR) for young or older patients compared to the middle-aged patients who serve as reference group. Red text indicates HRs with significant p-levels (not shown).

Table 4. Frequencies and proportions of first failures and subsequent metastatic disease.

	All				≤45 years				46–55 years				≥56 years
Type	N	%^a	n	%^b	N	%^a	n	%^b	N	%^a	n	%^b	N	%^a	n	%^b
All patients	1847	100	–	–	947	51	–	–	470	100 (26)	–	–	430	23	–	–
First failure
No recurrence	821	44.5	–	–	413	43.6	–	–	255	54.3	–	–	153	35.6	–	–
LRiso	233	12.6			154	16.3			39	8.3			40	9.3
later DM			75	36.6			59	38.3			3	7.7			13	32.5
RR +/- LRRsim	68	3.7			44	4.7			11	2.3			13	3.0
later DM			44	55.3			30	68.2			7	63.6			7	53.9
DMiso	410	22.2	–	–	210	22.2	–	–	89	18.9	–	–	111	25.8	–	–
CCiso	99	5.4			53	5.6			27	5.7			19	4.4
later DM			25	24.5			14	26.4			5	18.5			6	31.6
Other malignancy	144	7.8	–	–	55	5.8	–	–	39	8.3	–	–	50	11.6	–	–
later DM			4	<1			2	3.6			1	2.6			1	2.0
Death (no failure)	72	3.9	–	–	18	1.9	–	–	10	2.1	–	–	44	10.2

N: number of patients in sub-group defined as entire cohort or age group in combination with endpoint; %^a: percentages of patients with endpoint (calculated vertically); n: number of patients with subsequent distant metastases; %^b,percentages of patients with subsequent distant metastases (calculated horizontally). Notice that frequencies and proportions are calculated using all observation time.