Introduction
Materials and methods
Study design
Patient population
Lymphedema definition and measurement
Chemotherapy
Statistical analysis
Results
Patient population
Entire cohort
n = 1121 | Adjuvant taxane
n = 324 | No adjuvant taxane
n = 797 |
p valuea
| |
---|---|---|---|---|
Patient characteristics | ||||
Median age at surgery (months) | 57 | 53 (24–78) | 59 (30–89) | <0.0001 |
Median pre-operative body mass index (BMI)b (kg/m2) | 26.3 | 26.6 (16.8–50.4) | 26.2 (16.5–55.7) | 0.75 |
Median post-operative follow up (months) | 39.7 | 42.0 (18–100.4) | 38.5 (7.7–103.3) | 0.05 |
Breast surgery | <0.0001 | |||
Lumpectomy | 854 (76 %) | 207 (64 %) | 647 (81 %) | |
Mastectomy | 267 (24 %) | 117 (36 %) | 150 (19 %) | |
Axillary surgery | <0.0001 | |||
None | 164 (14 %) | 0 (0 %) | 164 (21 %) | |
Sentinel lymph node biopsy (SLNB) | 738 (66 %) | 165 (51 %) | 573 (72 %) | |
Axillary lymph node dissection (ALND) | 219 (20 %) | 159 (49 %) | 60 (8 %) | |
Tumor type | <0.0001 | |||
Invasive Carcinoma | 925 (83 %) | 320 (99 %) | 605 (76 %) | |
Ductal Carcinoma in Situ (DCIS) | 196 (17 %) | 4 (1 %) | 192 (24 %) | |
Pathologic characteristics | ||||
Median invasive tumor size, cm‡
| 1.4 (0.05–12.5) | 1.9 (0.2–12.5) | 1.1 (0.05–10.5) | <0.0001 |
Median number lymph nodes dissected | 2 (0–43) | 6 (1–43) | 1 (0–26) | <0.0001 |
Median number positive lymph nodes | 0 (0–39) | 1 (0–39) | 0 (0–26) | <0.0001 |
Radiation therapy | <0.0001 | |||
None | 216 (19 %) | 40 (12 %) | 176 (22 %) | |
Partial Breast Irradiation (PBI) | 96 (9 %) | 1 (0.3 %) | 95 (12 %) | |
Breast + Chest Wall only | 640 (57 %) | 148 (46 %) | 492 (62 %) | |
Breast + Chest Wall + Nodal Radiation (RLNR) | 167 (15 %) | 133 (41 %) | 34 (4 %) | |
Adjuvant chemotherapy | <0.0001 | |||
Yes | 386 (34 %) | 324 (100 %) | 62 (8 %) | |
No | 735 (66 %) | 0 (0 %) | 735 (92 %) | |
Adjuvant hormonal therapy | 0.20 | |||
Yes | 874 (78 %) | 79 (24 %) | 167 (21 %) | |
No | 246 (22 %) | 244 (76 %) | 630 (79 %) | |
Herceptin-based chemotherapy | <0.0001 | |||
Yes | 87 (8 %) | 75 (23 %) | 12 (2 %) | |
No | 1031 (92 %) | 248 (77 %) | 783 (98 %) |
Cumulative incidence of lymphedema
N
| 2-Year cumulative incidence (%) | 95 % Confidence interval | |
---|---|---|---|
Entire cohort | 1121 | 5.27 | 4.10–6.76 |
No chemotherapy | 735 | 3.07 | 2.03–4.63 |
Non-taxane chemotherapy | 62 | 4.87 | 1.60–14.33 |
Taxane-based chemotherapy | 324 | 10.29 | 7.43–14.18 |
Cumulative incidence of mild swelling
N
| 2-Year cumulative incidence (%) | 95 % Confidence interval | |
---|---|---|---|
Entire cohort | 1121 | 16.37 | 14.22–18.80 |
No chemotherapy | 735 | 14.64 | 12.20–17.53 |
Non-taxane chemotherapy | 62 | 7.05 | 2.71–17.71 |
Taxane-based chemotherapy | 324 | 22.76 | 18.19–28.28 |
Timing of swelling
Univariate analysis
Univariate results | Multivariate resultsc
| |||
---|---|---|---|---|
Hazard ratio (95 % CI) |
p value | Hazard ratio (95 % CI) |
p value | |
Patient characteristics | ||||
Age at surgery (years)a
| 1.02 (1.00–1.03) | 0.1080 | 1.02 (1.00–1.04) |
0.0433
|
Pre-operative BMIa (kg/m2) | 1.07 (1.04–1.10) | <0.0001 | 1.05 (1.02–1.09) |
0.0007
|
Surgical characteristics | ||||
Axillary surgery | ||||
SLNB versus no axillary surgery | 0.83 (0.36–1.89) | 0.6507 |
b
| – |
ALND versus no axillary surgery | 6.31 (2.88–13.80) | <0.0001 | 7.32 (3.16–17.01) | <0.0001 |
ALND versus SLNB/no axillary surgery | 7.37 (4.86–11.19) | <0.0001 | 8.19 (5.12–13.10) |
<0.0001
|
Pathologic characteristics | ||||
Invasive vs. DCIS | 2.20 (1.06–4.53) | 0.0335 | 1.05 (0.49–2.25) | 0.9041 |
Number positive lymph nodesa
| 1.10 (1.07–1.13) | <0.0001 | 1.02 (0.98–1.06) | 0.4337 |
Systemic therapy | ||||
Adjuvant taxane-based chemotherapy | ||||
Yes versus no chemo | 2.61 (1.73–3.95) | <0.0001 | 1.14 (0.69–1.87) | 0.6188 |
Yes versus non-taxane chemo | 2.90 (1.04–8.08) | 0.0412 | 1.56 (0.56–4.37) | 0.3988 |
Paclitaxel | ||||
Yes versus no chemo | 2.00 (1.23–3.24) | 0.0053 | 0.81 (0.46–1.41) | 0.4473 |
Yes versus non-taxane chemo | 2.45 (0.85–7.07) | 0.0984 | 1.26 (0.43–3.65) | 0.6725 |
Docetaxel | ||||
Yes versus no chemo | 2.54 (1.52–4.26) | 0.0004 | 1.25 (0.71–2.18) | 0.4374 |
Yes versus non-taxane chemo | 3.12 (1.06–9.20) | 0.0392 | 1.95 (0.65–5.85) | 0.2334 |
Non-taxane chemotherapy | ||||
Yes versus no chemo | 0.90 (0.32–2.52) | 0.8417 | 0.64 (0.22–1.83) | 0.4056 |
Hormonal therapy | ||||
Yes versus no | 1.59 (0.90–2.80) | 0.1098 | – | |
Herceptin-based chemotherapy | ||||
Yes versus no | 1.10 (0.55–2.20) | 0.7778 | – | – |
Radiation therapy | ||||
Yes versus no | 1.06 (0.65–1.75) | 0.8056 | – | – |
RLNR versus breast+chest wall/none | 4.32 (2.82–6.63) | <0.0001 | 1.29 (0.77– 2.16) | 0.3354 |
Univariate results | Multivariate resultsc
| |||
---|---|---|---|---|
Hazard Ratio (95 % CI) |
p value | Hazard Ratio (95 % CI) |
p value | |
Patient characteristics | ||||
Age at surgery (years)a
| 1.02 (1.01–1.03) | 0.0011 | 1.02 (1.01–1.03) |
0.0003
|
Pre-operative BMIa (kg/m2) | 1.02 (1.00–1.04) | 0.1366 | 1.01 (0.99–1.03) | 0.4157 |
Surgical characteristics | ||||
Axillary surgery | ||||
SLNB versus no axillary surgery | 0.90 (0.63–1.29) | 0.5631 |
–b
| – |
ALND versus no axillary surgery | 1.36 (0.89–2.07) | 0.1527 | 1.35 (0.84–2.18) | 0.2188 |
ALND versus SLNB/no axillary surgery | 1.48 (1.10–2.00) | 0.0105 | 1.47 (1.05–2.07) |
0.0266
|
Pathologic characteristics | ||||
Invasive vs. DCIS | 1.42 (0.99–2.04) | 0.0572 | 1.27 (0.87–1.84) | 0.2152 |
Number positive lymph nodesa
| 1.07 (1.03–1.11) | 0.0002 | 1.04 (0.99–1.00) | 0.0603 |
Systemic therapy | ||||
Adjuvant taxane-based chemo | ||||
Yes versus no chemo | 1.31 (1.00–1.71) | 0.0512 | 1.33 (0.97–1.83) | 0.0778 |
Yes versus non-taxane chemo | 1.86 (1.03–3.35) | 0.0398 | 1.74 (0.95–3.13) | 0.0732 |
Paclitaxel | ||||
Yes versus no-chemo | 1.16 (0.83–1.62) | 0.3882 | 1.13 (0.77–1.66) | 0.5428 |
Yes versus non-taxane chemo | 1.65 (0.88–3.07) | 0.1163 | 1.49 (0.79–2.80) | 0.2174 |
Docetaxel | ||||
Yes versus no-chemo | 1.62 (1.13–2.32) | 0.0084 | 1.63 (1.13–2.36) |
0.0098
|
Yes versus non-taxane chemo | 2.31 (1.21–4.38) | 0.0107 | 2.15 (1.13–4.09) |
0.0195
|
Non-taxane chemotherapy | ||||
Yes versus no chemo | 0.70 (0.40, 1.24) | 0.2265 | 0.75 (0.42–1.35) | 0.3473 |
Hormonal therapy | ||||
Yes versus no | 1.05 (0.78–1.41) | 0.7639 | – | – |
Herceptin-based chemotherapy | ||||
Yes versus no | 0.80 (0.50–1.30) | 0.3644 | – | – |
Radiation therapy | ||||
Yes versus no | 1.04 (0.77–1.40) | 0.8106 | – | – |
RLNR versus breast + chest wall/none | 1.18 (0.80–1.74) | 0.4043 | 0.82 (0.51–1.31) | 0.4064 |