Influence of specific comorbidities on survival after early-stage breast cancer

Figures & data

Table 1 Characteristics of 59,673 women diagnosed with early-stage breast cancer between 1990 and 2008 in Denmark.

	Characteristics of the study population
		Number of deaths
	Number of patients (%)	Breast cancer	Other causes
	59,673 (100)	20,381	10,648
Age at diagnosis
<40	2808 (5)	943	73
40–49	9875 (17)	2695	494
50–59	15,213 (25)	4396	1277
60–69	15,198 (25)	4855	2790
70–79	10,655 (18)	4456	3594
80+	5924 (10)	3036	2420
Tumor size
−10 mm	8257 (14)	1235	1454
11–20 mm	22,542 (38)	5638	4256
21–50 mm	22,267 (37)	9399	3874
51+ mm	2774 (5)	1797	346
Unknown	3833 (6)	2312	718
Histology and grade
Ductal I	14,192 (24)	3391	2948
Ductal II	19,649 (33)	6826	3320
Ductal III	10,587 (18)	4421	1276
Ductal unknown grade	1430 (2)	492	281
Lobular	6587 (11)	2320	1279
Other	4293 (7)	1011	953
Unknown	2935 (5)	1920	591
ER-status
Positive ≥10%	41,891 (70)	12581	7782
Poor <10%	11,734 (20)	4697	1547
Unknown	6048 (10)	3103	1319
Nodal status
Positive	25,943 (43)	11382	3355
Negative	31,079 (52)	7190	6798
Unknown	2651 (4)	1809	495
Surgery
Lumpectomy	19,047 (32)	3433	2389
Mastectomy	37,911 (64)	15042	7735
Biopsy only	2715 (6)	1906	524
Adjuvant therapy
None	15,915 (27)	3678	3094
Chemotherapy	7871 (13)	2723	465
Chemo- and endocrine treatment	4692 (8)	644	128
Endocrine alone	13,943 (23)	4302	2033
Unknown	17,302 (29)	9034	4928

Table 2. Comorbidity among 59,673 Danish women 0–5 and 5–10 years before diagnosis of breast cancer (BC) in relation to 5- and 10-year overall survival (OS) and breast cancer specific mortality (BCM).

	No. of patients	Disease before BC		No of deaths		5-year		10-year
		≤5 years	>5 years^a	BC	Other causes	OS % (95% CI)	BCM % (95% CI)	OS % (95% CI)	BCM % (95% CI)
Total	59673
None	49928			16616	7660	78.9 (78.5;79.2)	17.9 (17.6;18.2)	63.9 (63.5;64.3)	28.0 (27.6;28.4)
Myocardial infarction	831	562	322	351	305	56.7 (53.2;60.0)	28.6 (25.6;31.7)	34.3 (31.0;37.6)	39.2 (35.8;42.5)
Congestive heart failure	1168	958	302	502	511	42.4 (39.6;45.2)	33.5 (30.8;36.2)	18.3 (16.1;20.7)	42.5 (39.6;45.3)
Peripheral vascular disease	1076	837	365	430	397	54.6 (51.6;57.5)	28.9 (26.2;31.7)	30.1 (27.3;33.0)	38.2 (35.3;41.2)
Cerebrovascular disease	2154	1612	759	889	726	53.3 (51.2;55.4)	29.9 (27.9;31.8)	32.6 (30.5;34.6)	39.3 (37.2;41.4)
Dementia	369	325	64	211	132	28.1 (23.6;32.8)	48.0 (42.8;53.0)	09.3 (06.5;12.8)	56.8 (51.5;61.8)
Chronic pulmonary disease	2497	2018	888	901	764	62.0 (60.1;63.9)	24.4 (22.8;26.2)	40.4 (38.4;42.4)	34.2 (32.3;36.1)
Connective tissue disease	1236	928	563	428	329	66.7 (64.0;69.2)	22.5 (20.2;24.9)	46.1 (43.1;48.9)	33.0 (30.3;35.7)
Ulcer disease	1169	787	435	458	371	60.8 (58.0;63.6)	26.7 (24.2;29.3)	39.3 (36.4;42.2)	36.2 (33.4;39.0)
Liver disease	340	253	131	129	115	54.4 (49.0;59.5)	27.9 (23.3;32.8)	33.7 (28.5;39.0)	36.3 (31.1;41.5)
Diabetes	1843	1625	744	750	599	57.2 (54.9;59.4)	28.2 (26.2;30.3)	35.6 (33.3;37.8)	38.1 (35.8;40.3)
Hemiplegia	71	55	20	31	21	50.7 (38.6;61.6)	33.8 (23.0;44.9)	32.3 (21.5;43.7)	42.1 (30.0;53.7)
Renal disease	328	255	112	122	109	50.0 (44.5;55.3)	30.8 (25.9;35.8)	33.6 (28.4;38.8)	35.5 (30.4;40.7)

BC: breast cancer; OS: overall survival; BCM: breast cancer mortality; CI: confidence interval.

^a ≤10 years.

Table 3. Multivariable analysis of the hazard ratio (HR) of death from all causes and from breast cancer (BC) for 12 comorbidities with breast cancer patients without comorbidities as reference category.

	All cause mortality HR (95% CI)			BC mortality HR (95% CI)
	Unadjusted	Age adjusted^a	Fully adjusted^b	Unadjusted	Age adjusted^a	Fully adjusted^b
Myocardial infarction	1.52 (1.40;1.65)	1.20 (1.11;1.30)	1.23 (1.14;1.33)	1.20 (1.07;1.35)	1.08 (0.96;1.21)	1.10 (0.98;1.24)
Congestive heart failure	2.22 (2.07;2.37)	1.42 (1.33;1.52)	1.42 (1.33;1.52)	1.28 (1.15;1.41)	0.99 (0.90;1.10)	0.99 (0.89;1.10)
Peripheral vascular disease	1.69 (1.57;1.81)	1.43 (1.33;1.53)	1.52 (1.42;1.64)	1.19 (1.07;1.32)	1.06 (0.96;1.18)	1.13 (1.01;1.27)
Cerebrovascular disease	1.81 (1.72;1.91)	1.30 (1.23;1.37)	1.30 (1.23;1.37)	1.26 (1.17;1.35)	1.05 (0.97;1.13)	1.05 (0.97;1.13)
Dementia	3.47 (3.12;3.87)	1.79 (1.61;2.00)	1.61 (1.44;1.80)	2.13 (1.82;2.50)	1.51 (1.28;1.78)	1.33 (1.13;1.58)
Chronic pulmonary disease	1.48 (1.40;1.55)	1.44 (1.37;1.52)	1.58 (1.50;1.66)	1.08 (1.00;1.16)	1.05 (0.97;1.12)	1.18 (1.10;1.28)
Connective tissue disease	1.28 (1.19;1.38)	1.14 (1.06;1.22)	1.22 (1.13;1.31)	1.02 (0.93;1.13)	0.95 (0.86;1.05)	1.01 (0.90;1.12)
Ulcer disease	1.49 (1.39;1.59)	1.21 (1.13;1.30)	1.28 (1.19;1.37)	1.15 (1.04;1.27)	1.03 (0.94;1.14)	1.09 (0.98;1.21)
Liver disease	1.76 (1.55;2.00)	2.01 (1.77;2.28)	2.25 (1.98;2.56)	1.15 (0.95;1.38)	1.23 (1.02;1.48)	1.41 (1.15;1.71)
Diabetes	1.58 (1.49;1.67)	1.39 (1.31;1.47)	1.33 (1.26;1.41)	1.22 (1.13;1.32)	1.13 (1.04;1.22)	1.05 (0.96;1.14)
Hemiplegia	1.59 (1.21;2.09)	1.52 (1.15;2.00)	1.42 (1.08;1.87)	1.33 (0.90;1.95)	1.27 (0.86;1.88)	1.27 (0.87;1.86)
Renal disease	1.42 (1.25;1.62)	1.46 (1.28;1.66)	1.69 (1.48;1.92)	1.07 (0.88;1.31)	1.07 (0.87;1.31)	1.26 (1.02;1.56)

HR: hazard ratio; BC: breast cancer; CI: confidence interval.

^aIn 5-year categories.

^b Adjusted for age, year of surgery, tumor size, lymph node status, lymphovascular invasion, invasion resection margin, histological type and grade, hormone receptor status, menopausal status, treatment.

Table 4. Interaction between diabetes and vascular comorbidities on the hazard ratio of death from breast cancer with breast cancer patients without comorbidity as reference.

	Vascular morbidity No diabetes	Diabetes No vascular morbidity	Diabetes and Vascular morbidity
	HR (95% CI)	HR (95% CI)	HR (95% CI)	p test of interaction
Myocardial infarction	1.11 (0.97;1.26)	1.05 (0.96;1.15)	1.12 (0.82;1.51)	.82
Congestive heart failure	1.03 (0.92;1.16)	1.08 (0.99;1.18)	0.83 (0.64;1.08)	.05
Peripheral vascular disease	1.17 (1.04;1.33)	1.07 (0.98;1.17)	0.94 (0.68;1.30)	.11
Cerebrovascular disease	1.05 (0.96;1.14)	1.05 (0.96;1.14)	1.10 (0.88;1.38)	.97
Renal disease	1.21 (0.96;1.51)	1.04 (0.96;1.13)	1.59 (0.94;2.70)	.42

HR: hazard ratio; CI: confidence interval.

Figure 1. Hazard ratio of death from all causes in relation to time period of comorbidity with breast cancer patients without comorbidity as reference.

Figure 2. Hazard ratio of death from breast cancer in relation to receipt of adjuvant chemotherapy (CT) and adjuvant endocrine treatment (ET) with breast cancer patients without comorbidity as reference.