Heavy-load resistance exercise during chemotherapy in physically inactive breast cancer survivors at risk for lymphedema: a randomized trial

Figures & data

Figure 1. Flow of participants from recruitment and through the trial including 153 women receiving adjuvant chemotherapy for primary breast cancer. Copenhagen University Hospitals, Herlev and Rigshospitalet, 2014–2016.

Table 1. Baseline characteristics of 153 women receiving adjuvant chemotherapy for primary breast cancer. Copenhagen University Hospitals, Herlev and Rigshospitalet, 2014–2016.

Characteristics	Total (n = 153)	HIGH (n = 75)	LOW (n = 78)
Age (years), mean ± SD	51.7 ± 9.4	51.5 ± 9.6	52.0 ± 9.3
BMI (kg/m^2), mean ± SD	26.1 ± 5.1	26.2 ± 5.3	26.0 ± 4.9
Cancer stage, n (%)
Stage 1	56 (36.6%)	31 (41.3%)	25 (31.1%)
Stage 2	81 (52.9%)	36 (48.0%)	45 (57.7%)
Stage 3	16 (10.5%)	8 (10.7%)	8 (10.3%)
Breast surgery, n (%)
Lumpectomy	90 (58.8%)	47 (62.7%)	43 (55.1%)
Mastectomy	56 (36.6%)	26 (34.7%)	30 (38.5%)
Mastectomy plus expander	7 (4.6%)	2 (2.7%)	5 (6.4%)
Axillary surgery, n (%)
Axillary lymph node dissection	61 (39.9%)	26 (34.7%)	35 (44.9%)
Sentinel node biopsy	92 (60.1%)	49 (65.3%)	43 (55.1%)
Nodes removed, median (IQR)	3 (2-17)	3 (1-15)	5 (2-19)
Surgery on dominant side, n (%)	76 (49.7%)	39 (52.0%)	37 (47.4%)
Missing data n (%)	4 (2.6 %)	1 (1.3%)	3 (3.9%)
No. of seroma drainages, median (IQR)	1 (0-5)	1 (0-5)	1 (0-5)
Chemotherapy, n (%)
3-wkly CE x 3 -> 3 wkly docetaxel x 3	130 (85.0%)	66 (86.7%)	64 (82.1%)
3-wkly CE x 3 -> 1 wkly paclitaxel x 9	19 (12.4%)	8 (10.7%)	11 (14.1%)
Other	4 (2.6%)	1 (1.3%)	3 (3.9%)
Observations of swelling, n (%)
Extremity (hand, underarm, overarm)	5 (3.3%)	2 (2.7%)	3 (3.9%)
Body (breast, torso)	31 (20.5%)	14 (18.9%)	17 (22.1%)
Both (body & extremity)	11 (7.3%)	3 (4.1%)	8 (10.4%)
Missing data n (%)	2 (1.3%)	1 (1.3%)	1 (1.3%)
Treatment related to lymphedema, n (%)
Preventatively	4 (2.6%)	1 (1.4%)	3 (3.9%)
Existing lymphedema	5 (3.3%)	1 (1.4%)	4 (5.2%)
Missing data n (%)	2 (1.3%)	1 (1.3%)	1 (1.3%)
Symptom subscales EORTC-BR23
Arm symptoms, mean ± SD	16.2 ± 19.0	15.6 ± 20.1	16.8 ± 18.0
Breast symptoms, mean ± SD	18.9 ± 16.1	18.6 ± 16.4	19.2 ± 16.0
L-Dex, mean ± SD	−0.3 ± 5.1	−0.6 ± 3.6	0.1 ± 6.2
Missing data^a n (%)	73 (47.7%)	36 (48%)	37 (47.4%)
Volume % difference, mean ± SD	1.3 ± 19.8	0.6 ± 19.7	1.9 ± 20.0
Missing data^b n (%)	35 (22.9%)	20 (26.7%)	15 (19.2%)
1 RM upper-extremity strength (kg), mean ± SD	29.4 ± 8.3	29.0 ± 8.1	29.8 ± 8.6
Missing data^c n (%)	15 (9.8%)	4 (5.3%)	11 (14.1%)

^aBioimpedance spectroscopy not performed (n = 70) missing (n = 1), bilateral axillary surgery (n = 2); ^bBilateral axillary surgery (n = 5), exceeded DXA scan area (n = 30, LOW (n = 13, mean BMI 32 ± 5.6) HIGH (n = 17, mean BMI 33 ± 5.5); ^cPost-surgery restrictions (n = 14), precautionary due to arm swelling (n = 1).

BMI: body mass index; CE: cyclophosphamide & epirubicin; EORTC QLQ-BR23: European Organization for Research and Treatment of Cancer Breast Cancer Module; IQR: interquartile range; no: number; pctl: percentile; SD: standard deviation.

Table 2. Point prevalence (N (%)) of lymphedema (L-Dex >10, inter-arm volume difference > 5% and self-reported swelling) based on all available data for each outcome, in 153 women receiving adjuvant chemotherapy for primary breast cancer. Copenhagen University Hospitals, Herlev and Rigshospitalet, 2014–2016.

	Baseline		12 weeks		39 weeks
	n	N (%)	n	N (%)	n^a	N (%)
L-Dex > 10
HIGH	39	0 (0.0%)	33	3 (9.1%)	41	4 (9.8%)
LOW	41	2 (4.9%)	31	2 (6.5%)	34	3 (8.8%)
Inter-arm volume % difference > 5%^b
HIGH	55	15 (27.3%)	45	14 (31.1%)	50	12 (24.0%)
LOW	63	15 (23.8%)	51	13 (25.5%)	49	13 (26.5%)
Observed difference in size between sides within the last week^c
HIGH	74	19 (25.7%)	62	18 (29.0%)	62	21 (33.9%)
LOW	77	28 (36.4%)	63	13 (20.6%)	59	22 (37.3%)

^a At 39 weeks BIS measures were included for twelve participants with no previous BIS measures; ^bn = 30, 28, 14 exceeded DXA scan area, respectively at baseline, 12 and 39 weeks and were therefore not included in the analysis; ^cOf the participants that observed size difference at baseline, 12 and 39 weeks; 31 (66%), 8 (25.8%), and 17 (39.5%) respectively, reported swelling located to the body (breast, torso) only.

Table 3. Equivalence between groups for lymphedema outcomes in 153 women receiving adjuvant chemotherapy for primary breast cancer. Copenhagen University Hospitals, Herlev and Rigshospitalet, 2014–2016.

		Mean difference*	Equivalence 90% CI
L-Dex (±5.0)^a (n = 81)	n
12 weeks	64	0.4	−2.5 to 3.2
39 weeks	63	0.7	−2.2 to 3.6
Inter-arm volume % difference (±3.0)^a (n = 148)
12 weeks^ǂ	86	−3.5	−17.3 to 10.3^b
39 weeks^ǂ	83	−1.7	−7.7 to 4.3^b
Pain (±1.0)^a (n = 153)
12 weeks	124	−0.7	−1.3 to 0^b
39 weeks	121	−0.8	−1.5 to −0.1^b
Heaviness (±1.0)^a (n = 153)
12 weeks	124	−0.2	−0.6 to 0.2
39 weeks	121	0.0	−0.7 to 0.6
Tightness (±1.0)^a (n = 153)
12 weeks	124	−0.1	−0.8 to 0.6
39 weeks	121	−1.0	−1.8 to 0.2^b
Swelling (±1.0)^a (n = 153)
12 weeks	124	0.2	−0.4 to 0.8
39 weeks	120	0.0	−0.8 to 0.7

*Mean difference between groups with HIGH as comparator (HIGH minus LOW); ^aPre-determined equivalence margin; ^ǂn = 28 and 14 not included at 12 and 39 weeks respectively, due to body dimension exceeding the DXA scan area; Bold: equivalence not demonstrated; ^bnegative deviation reflecting reductions beyond the equivalence margin favoring the HIGH group.

Table 4. Within group changes and between group differences for upper-extremity strength and breast cancer-specific functional and symptom domains in 153 women receiving adjuvant chemotherapy for primary breast cancer. Copenhagen University Hospitals, Herlev and Rigshospitalet, 2014–2016.

	Δ 6 weeks-baseline			Δ 12 weeks-baseline			Δ 39 weeks-baseline
Variable	n	Mean Δ (95% CI)	Group difference (95% CI)	n	Mean Δ (95% CI)	Group difference (95% CI)	n	Mean Δ (95% CI)	Group difference (95% CI)
Muscular strength 1 RM (kg)*
Chest press
HIGH	58	5 (3:6)	4 (2:6)	56	4 (3:6)	3 (1:5)	50	3 (1:5)	2 (0:5)
LOW	51	1 (−1:2)		55	1 (0:3)		44	1 (−1:3)
EORTC QLQ-BR23 scores**
Body Image
HIGH	62	2 (−3:7)	4 (−3:10)	60	−3 (−9:2)	2 (−5:10)	61	7 (2:11)^a	1 (−6:8)
LOW	61	−1 (−6:3)		62	−6 (−11:-1)		56	6 (1:11)^a
Systemic therapy^ǂ
HIGH	63	5 (1:10)^a	1 (−6:8)	61	7 (2:12)^a	−2 (−9:6)	61	−19 (−23:−15)^b	1 (−5:7)
LOW	62	4 (−1:9)		65	9 (4:14)^a		57	−20 (−24:−16)^c
Breast symptoms
HIGH	62	−6 (−9: −2)^a	1 (−4:6)	60	−11 (−15:−7)^b	−2 (−8:3)	59	−4 (−9:1)	−4 (−12:3)
LOW	62	−7 (10: −3)^a		64	−9 (−12: −5)^a		55	1 (−4:6)
Arm symptoms
HIGH	62	−4 (−8:0)^a	1 (−5:7)	60	−6 (−10:-1)^a	−2 (−8:4)	59	−1 (−6:4)	−4 (−12:3)
LOW	62	−5 (−10: −1)^a		65	−4 (−8:1)		56	3 (−2:9)

CI, confidence interval; Bold: statistical difference (p < .05); *No upper-extremity strength measures on one participant (LOW) at baseline due to visible and untreated swelling. No upper-extremity strength assessment at subsequent data collections as the participant was receiving treatment for lymphedema. Three participants (2 HIGH, 1 LOW) were not assessed for upper-extremity strength at 6, 12 and 39 weeks, as a precautionary measure due to swelling or because participants refused. An additional participant (HIGH) received treatment for lymphedema at 12 and 39 weeks and was therefore not tested; **Higher functional scores (body image) indicate higher levels of functioning, lower symptom scores (systemic therapy, arm and breast symptoms) indicate a reduction in symptoms; ^ǂPerceived treatment burden; ^a,b,cSubjective significance of changes from baseline in terms of ^a‘small’, ^b’moderate’, ^c’large’ (Osoba 1998).