Introduction
Materials and methods
Study setting, subjects, and recruitment
Data collection
Arm lymphedema
Breast cancer-related and treatment-related factors
Sociodemographic and lifestyle factors
Health-related and hormone-related factors
Statistical analysis
Results
Characteristics of study population
Age- and race/ethnicity-adjusted analyses
Characteristics | Categories | N at risk | LE (%) | HR (95% CI)a | HR (95% CI)b |
---|---|---|---|---|---|
Breast cancer and treatment | |||||
Age at diagnosis (years) | 35-44 | 123 | 43 (35.0) | 1.00 | 1.00 |
45-49 | 128 | 43 (33.6) | 0.98 (0.64 - 1.50) | 0.98 (0.63 - 1.52) | |
50-54 | 175 | 46 (26.3) | 0.80 (0.52 - 1.21) | 0.79 (0.51 - 1.23) | |
55-59 | 128 | 35 (27.3) | 0.83 (0.53 - 1.30) | 0.78 (0.49 - 1.23) | |
60-64 | 112 | 23 (20.5) | 0.59 (0.35 - 0.97) | 0.61 (0.35 - 1.06) | |
Per unit of age | 0.98 (0.96 - 1.00) | 0.98 (0.96 - 1.00) | |||
P trend = 0.03
|
P trend = 0.04
| ||||
Disease stage |
In situ
| 155 | 15 (9.7) | 0.26 (0.15 - 0.45) | |
Localized | 346 | 105 (30.4) | 1.00 | ||
Regional | 165 | 70 (42.4) | 1.35 (0.99 - 1.85) | ||
Tumor size (mm) | <10 | 178 | 36 (20.2) | 1.00 | |
10-19 | 216 | 66 (30.6) | 1.54 (1.02 - 2.32) | ||
20+ | 208 | 76 (36.5) | 1.85 (1.23 - 2.77) | ||
Missing | 64 | 12 (18.8) | 0.80 (0.41 - 1.54) | ||
Per mm | 1.01 (1.00 - 1.02) | ||||
P trend = 0.02
| |||||
Cancer location | Nipple, central portion, upper/lower inner quadrant | 143 | 44 (30.8) | 1.15 (0.80 - 1.66) | |
Upper/lower outer quadrant | 292 | 83 (28.4) | 1.00 | ||
Overlapping lesion | 147 | 44 (29.9) | 1.07 (0.74 - 1.55) | ||
Axillary tail, NOS | 84 | 19 (22.6) | 0.75 (0.46 - 1.24) | ||
Surgery type | Partial/less than total mastectomy/surgery, NOS | 442 | 108 (24.4) | 1.00 | 1.00 |
Total mastectomy/modified radical mastectomy | 224 | 82 (36.6) | 1.52 (1.13 - 2.04) | 1.37 (1.01 - 1.85) | |
Reconstructive surgery | No | 533 | 150 (28.1) | 1.00 | |
Yes | 105 | 33 (31.4) | 0.98 (0.67 - 1.45) | ||
Missing | 28 | 7 (25.0) | - | ||
Number of excised lymph nodes | 0 | 143 | 9 (6.3) | 0.13 (0.06 - 0.25) | 0.17 (0.08 - 0.33) |
1-9c | 162 | 32 (19.8) | 0.44 (0.30 - 0.64) | 0.46 (0.31 - 0.68) | |
10+ | 361 | 149 (41.3) | 1.00 | 1.00 | |
Per lymph node | 1.06 (1.04 - 1.08) | 1.05 (1.03 - 1.07) | |||
P trend <0.001
|
P trend < 0.001
| ||||
Radiation | No | 270 | 73 (27.0) | 1.00 | |
Yes | 396 | 117 (29.6) | 1.21 (0.90 - 1.63) | ||
Chemotherapy | No | 413 | 83 (20.1) | 1.00 | 1.00 |
Yes | 253 | 107 (42.3) | 2.28 (1.69 - 3.09) | 1.48 (1.09 - 2.02) | |
Tamoxifen | No | 382 | 96 (25.1) | 1.00 | |
Yes | 284 | 94 (33.1) | 1.58 (1.18 - 2.12) | ||
Sociodemographic factors
| |||||
Race/ethnicity | Non-Hispanic white (NM, WW) | 371 | 88 (23.7) | 1.00 | 1.00 |
Black (LA) | 226 | 82 (36.3) | 1.62 (1.20 - 2.20) | 1.16 (0.83 - 1.61) | |
Hispanic white (NM) | 69 | 20 (29.0) | 1.19 (0.73 - 1.94) | 1.04 (0.63 - 1.70) | |
Marital status | Married | 445 | 123 (27.6) | 1.00 | |
Widowed | 34 | 10 (29.4) | 1.25 (0.64 - 2.43) | ||
Divorced/separated | 140 | 46 (32.9) | 1.20 (0.86 - 1.69) | ||
Never married | 47 | 11 (23.4) | 0.85 (0.45 - 1.58) | ||
Education | High school or less | 158 | 48 (30.4) | 1.00 | |
Some college | 249 | 75 (30.1) | 0.92 (0.63 - 1.33) | ||
College graduate | 120 | 39 (32.5) | 1.14 (0.73 - 1.77) | ||
Graduate studies | 139 | 28 (20.1) | 0.65 (0.40 - 1.07) | ||
Insurance | Yes | 618 | 180 (29.1) | 1.00 | |
No | 25 | 8 (32.0) | 1.04 (0.51 - 2.12) | ||
Missing | 23 | 2 (8.7) | - | ||
Health-related factors
| |||||
Body mass index prior to diagnosis (kg/m2) | <25 | 306 | 70 (22.9) | 1.00 | 1.00 |
25-29.9 | 220 | 67 (30.5) | 1.40 (0.99 - 1.96) | 1.25 (0.88 - 1.76) | |
30+ | 140 | 53 (37.9) | 1.83 (1.27 - 2.63) | 1.59 (1.09 - 2.31) | |
Per unit of BMI | 1.04 (1.02 - 1.07) | 1.04 (1.01 - 1.06) | |||
P trend < 0.001
|
P trend = 0.01
| ||||
Menopausal statusd | Premenopausal | 259 | 82 (31.7) | 1.00 | |
Postmenopausal | 341 | 80 (23.5) | 0.81 (0.51 - 1.28) | ||
Unknown | 66 | 28 (42.4) | 1.44 (0.91 - 2.26) | ||
Hypertension | No | 468 | 122 (26.1) | 1.00 | 1.00 |
Yes | 198 | 68 (34.3) | 1.54 (1.11 - 2.12) | 1.49 (1.06 - 2.10) | |
Diabetes | No | 607 | 174 (28.7) | 1.00 | |
Yes | 59 | 16 (27.1) | 0.96 (0.57 - 1.62) | ||
Arthritis | No | 480 | 135 (28.1) | 1.00 | |
Yes | 186 | 55 (29.6) | 1.19 (0.86 - 1.65) | ||
Charlson Comorbidity Index | 0 | 599 | 177 (29.6) | 1.00 | |
1-2 | 65 | 13 (20.0) | 0.70 (0.40 - 1.24) | ||
Missing | 2 | 0 (0.0) | - | ||
Hormonal factors
| |||||
Oral contraceptives use prior to diagnosis | No | 189 | 48 (25.4) | 1.00 | |
Yes | 477 | 142 (29.8) | 1.12 (0.79 - 1.58) | ||
Estrogen use prior to diagnosisd,e | No | 120 | 26 (21.7) | 1.00 | |
Yes | 210 | 52 (24.8) | 1.36 (0.83 - 2.24) | ||
Missing | 11 | 2 (18.2) | - | ||
Progestin use prior to diagnosisd,e | No | 205 | 52 (25.4) | 1.00 | |
Yes | 119 | 23 (19.3) | 0.94 (0.56 - 1.59) | ||
Missing | 17 | 5 (29.4) | - | ||
Lifestyle factors
| |||||
Pack-years of smoking | <100 cigarettes in lifetime, <0.05 pack-years | 326 | 92 (28.2) | 1.00 | |
0.05-5.3 pack-years | 112 | 33 (29.5) | 1.06 (0.71 - 1.58) | ||
5.4-20.5 pack-years | 111 | 37 (33.3) | 1.31 (0.89 - 1.93) | ||
>20.5 pack-years | 114 | 27 (23.7) | 0.93 (0.60 - 1.44) | ||
Missing | 3 | 1 (33.3) | - | ||
Per pack-year of smoking | 1.00 (0.99 - 1.01) | ||||
P trend = 0.47
| |||||
Alcohol intake year prior to diagnosis (grams per day) | <1 | 329 | 102 (31.0) | 1.00 | |
1-6 | 99 | 25 (25.3) | 0.82 (0.52 - 1.28) | ||
>6 | 117 | 29 (24.8) | 0.94 (0.61 - 1.45) | ||
Missing | 121 | 34 (28.1) | 1.28 (0.79 - 2.09) | ||
Per gram of alcohol | 0.99 (0.97 - 1.01) | ||||
P trend = 0.42
| |||||
Sports and recreational activities year prior to diagnosis (MET hours/week) | <0.5 | 223 | 68 (30.5) | 1.00 | |
0.5-20.0 | 298 | 85 (28.5) | 1.13 (0.80 - 1.59) | ||
>20.0 | 144 | 37 (25.7) | 1.09 (0.71 - 1.67) | ||
Missing | 1 | 0 (0.0) | - | ||
Per MET hour | 1.00 (0.99 - 1.01) | ||||
P trend = 0.80
|
Multivariable analyses overall
Multivariable analyses by timing of lymphedema onset
Characteristics | Categories | Early LE/ at risk | Late LE/ at risk | Early-onset LE HR (95% CI)a | Late-onset LE HR (95% CI)a | Pfor interactionb |
---|---|---|---|---|---|---|
Breast cancer and treatment
| ||||||
Age at diagnosis (years) | 35-44 | 18/123 | 25/105 | 1.00 | 1.00 | |
45-49 | 22/128 | 21/106 | 1.19 (0.63 - 2.24) | 0.83 (0.46 - 1.51) | ||
50-54 | 29/175 | 17/146 | 1.19 (0.65 - 2.17) | 0.51 (0.27 - 0.96) | ||
55-59 | 20/128 | 15/108 | 1.04 (0.54 - 2.00) | 0.59 (0.31 - 1.12) | ||
60-64 | 16/112 | 7/96 | 1.03 (0.50 - 2.10) | 0.31 (0.13 - 0.74) |
0.15
| |
Per unit of age | 1.00 (0.97 - 1.03) | 0.95 (0.92 - 0.98) | 0.02 | |||
P trend = 0.91
|
P trend = 0.002
| |||||
Surgery type | Partial/less than total mastectomy/surgery, NOS | 57/442 | 51/385 | 1.00 | 1.00 | |
Total mastectomy/modified radical mastectomy | 48/224 | 34/176 | 1.41 (0.95 - 2.09) | 1.32 (0.84 - 2.06) |
0.82
| |
Number of excised lymph nodes | 0 | 5/143 | 4/138 | 0.20 (0.08 - 0.51) | 0.13 (0.05 - 0.37) | |
1-9c | 19/162 | 13/143 | 0.57 (0.34 - 0.95) | 0.36 (0.20 - 0.65) | ||
10+ | 81/361 | 68/280 | 1.00 | 1.00 |
0.44
| |
Per lymph node | 1.04 (1.01 - 1.06) | 1.06 (1.03 - 1.09) |
0.20
| |||
P trend = 0.003
|
P trend <0.001
| |||||
Chemotherapy | No | 47/413 | 36/366 | 1.00 | 1.00 | |
Yes | 58/253 | 49/195 | 1.28 (0.86 - 1.91) | 1.77 (1.13 - 2.78) |
0.27
| |
Sociodemographic factors
| ||||||
Race/ethnicity | Non-Hispanic white (NM, WW) | 50/371 | 38/321 | 1.00 | 1.00 | |
Black (LA) | 45/226 | 37/181 | 1.08 (0.70 - 1.65) | 1.26 (0.79 - 2.02) | ||
Hispanic white (NM) | 10/69 | 10/59 | 0.90 (0.45 - 1.78) | 1.24 (0.61 - 2.50) |
0.77
| |
Health-related factors
| ||||||
Body mass index prior to diagnosis (kg/m2) | <25 | 37/306 | 33/269 | 1.00 | 1.00 | |
25-29.9 | 36/220 | 31/184 | 1.24 (0.78 - 1.98) | 1.25 (0.76 - 2.06) | ||
30+ | 32/140 | 21/108 | 1.64 (1.00 - 2.67) | 1.52 (0.87 - 2.66) |
0.97
| |
Per unit of BMI | 1.03 (1.00 - 1.07) | 1.04 (1.00 - 1.08) |
0.91
| |||
P trend = 0.05
|
P trend = 0.07
| |||||
Hypertension | No | 63/468 | 59/405 | 1.00 | 1.00 | |
Yes | 42/198 | 26/156 | 1.65 (1.08 - 2.54) | 1.30 (0.80 - 2.13) |
0.44
|
Multivariable analyses stratified by race/ethnicity
Non-Hispanic white | Black | Hispanic white | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Characteristics | Categories | N | LE (%) | HR (95% CI)a | N | LE (%) | HR (95% CI)a | N | LE (%) | HR (95% CI)a | Pfor interactionb |
Age at diagnosis (years) | 35-44 | 56 | 19 (33.9) | 1.00 | 53 | 21 (39.6) | 1.00 | 14 | 3 (21.4) | 1.00 | |
45-49 | 65 | 16 (24.6) | 0.90 (0.45 - 1.77) | 46 | 20 (43.5) | 1.00 (0.53 - 1.92) | 17 | 7 (41.2) | 2.23 (0.50 - 10.07) | ||
50-54 | 112 | 28 (25.0) | 0.77 (0.42 - 1.40) | 48 | 17 (35.4) | 0.87 (0.44 - 1.72) | 15 | 1 (6.7) | 0.40 (0.04 - 4.30) | ||
55-59 | 77 | 17 (22.1) | 0.74 (0.38 - 1.44) | 37 | 13 (35.1) | 0.69 (0.33 - 1.44) | 14 | 5 (35.7) | 2.77 (0.56 - 13.77) | ||
60-64 | 61 | 8 (13.1) | 0.42 (0.17 - 1.00) | 42 | 11 (26.2) | 0.60 (0.26 - 1.34) | 9 | 4 (44.4) | 9.17 (1.43 - 58.94) |
0.24
| |
Surgery type | Partial/less than total mastectomy/ surgery, NOS | 272 | 53 (19.5) | 1.00 | 123 | 43 (35.0) | 1.00 | 47 | 12 (25.5) | 1.00 | |
Total/modified radical mastectomy | 99 | 35 (35.4) | 1.58 (1.02 - 2.45) | 103 | 39 (37.9) | 1.15 (0.72 - 1.81) | 22 | 8 (36.4) | 2.16 (0.71 - 6.54) |
0.39
| |
Number of excised lymph nodes | 0 | 88 | 3 (3.4) | 0.10 (0.03 - 0.32) | 41 | 5 (12.2) | 0.41 (0.16 - 1.10) | 14 | 1 (7.1) | 0.09 (0.01 - 0.80) | |
1-9c | 100 | 18 (18.0) | 0.48 (0.28 - 0.82) | 49 | 13 (26.5) | 0.64 (0.35 - 1.18) | 13 | 1 (7.7) | 0.09 (0.01 - 0.70) | ||
10+ | 183 | 67 (36.6) | 1.00 | 136 | 64 (47.1) | 1.00 | 42 | 18 (42.9) | 1.00 |
0.48
| |
Chemotherapy | No | 250 | 43 (17.2) | 1.00 | 124 | 27 (21.8) | 1.00 | 39 | 13 (33.3) | 1.00 | |
Yes | 121 | 45 (37.2) | 1.25 (0.80 - 1.95) | 102 | 55 (53.9) | 2.69 (1.61 - 4.50) | 30 | 7 (23.3) | 0.69 (0.24 - 2.03) | 0.01 | |
Body mass index (kg/m2) | <25 | 192 | 42 (21.9) | 1.00 | 89 | 23 (25.8) | 1.00 | 25 | 5 (20.0) | 1.00 | |
25-29.9 | 114 | 26 (22.8) | 1.05 (0.64 - 1.73) | 76 | 32 (42.1) | 1.58 (0.90 - 2.78) | 30 | 9 (30.0) | 2.25 (0.65 - 7.72) | ||
30+ | 65 | 20 (30.8) | 1.50 (0.86 - 2.61) | 61 | 27 (44.3) | 1.65 (0.91 - 2.98) | 14 | 6 (42.9) | 3.94 (0.99 - 15.75) |
0.46
| |
Hypertension | No | 292 | 73 (25.0) | 1.00 | 119 | 30 (25.2) | 1.00 | 57 | 19 (33.3) | 1.00 | |
Yes | 79 | 15 (19.0) | 0.95 (0.52 - 1.74) | 107 | 52 (48.6) | 2.73 (1.65 - 4.53) | 12 | 1 (8.3) | 0.21 (0.02 - 2.00) | <0.001 |