Abstract

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

Kira Bloomquist, Lis Adamsen, Sandra C. Hayes, Christian Lillelund, Christina Andersen, Karl Bang Christensen, Peter Oturai, Bent Ejlertsen, Malgorzata K. Tuxen & Tom Møller. Acta Oncologica, 58:12, 1667-1675.

Background: Due to long-standing concerns that heavy-load lifting could increase the risk of developing lymphedema, breast cancer survivors have been advised to refrain from resistance exercise with heavy loads. This study prospectively evaluated the effect of heavy-load resistance exercise on lymphedema development in women receiving chemotherapy for breast cancer.

Material and Methods: Physically inactive women receiving adjuvant chemotherapy for breast cancer (n¼153) were randomized to a HIGH (supervised, multimodal exercise including heavy-load resistance exercise: 85–90% 1 repetition maximum [RM], three sets of 5–8 repetitions) versus LOW (pedometer and one-on-one consultations) 12-week intervention. Outcomes (baseline, 12 and 39 weeks) included lymphedema status (extracellular fluid [bioimpedance spectroscopy] and inter-arm volume % difference [dual-energy X-ray absorptiometry], lymphedema symptoms [numeric rating scale 0–10]), upperextremity strength (1 RM), and quality of life domains (EORTC- BR23). Linear mixed models were used to evaluate equivalence between groups for lymphedema outcomes (equivalence margins for L-Dex, % difference and symptoms scale: ±5, ±3% and ±1, respectively). Superiority analysis was conducted for muscle strength and quality of life domains.

Results: Post intervention equivalence between groups was found for extracellular fluid (0.4; 90% CI – 2.5 to 3.2) and symptoms of heaviness (- 0.2; -0.6 to 0.2), tightness -(0.1;- 0.8 to 0.6) and swelling (0.2; – 0.4 to 0.8). Nonequivalence was found for inter-arm volume % difference (-3.5%; -17.3 to 10.3) and pain (0.7; 1.3 to 0), favoring HIGH. Strength gains were superior in the HIGH versus LOW group (3kg; 1 to 5, p<.05). Further, clinically relevant reductions in breast (-11; -15 to 7) and arm (-6; -10 to -1) symptoms were found in the HIGH group.

Conclusion: Findings suggest that physically inactive breast cancer survivors can benefit from supervised heavy-load resistance exercise during chemotherapy without increasing lymphedema risk.

Main findings

• N = 153
• Randomised into high and low groups
• High Group
  • HIGH group participated in a supervised twelve-week, group-based exercise program. The first six weeks consisted of a previously described exercise program ‘Body and Cancer’ [20,23,24], which entailed multimodal sessions including low- and high-intensity components.
  • The following six weeks consisted of an ‘All sport’ exercise program focusing on high-intensity components combined with other aerobic activities performed at moderate to high intensities. (Supplementary Table 1)[ 20]. The high-intensity component included an aerobic-based warmup followed by resistance exercise and 15–30minutes of cardiovascular interval training on stationary bikes with peak loads equivalent to 85–95% maximal heart rate. The resistance exercise program comprised of six machine-based exercises (TechnogymV R, Gamettola, Italy) targeting major muscle groups of the body including the chest press and latissimus pull down. Resistance exercise loads were based on a 1 RM strength test performed during the first exercise session.
  • During the first week, participants were instructed to lift loads corresponding to 2–3 sets of 8–12 repetitions at 70% 1 RM, progressing to 80% 1 RM in week two. From week three forward, loads lifted corresponded to 3 sets of 5–8 repetitions at 80–90% 1 RM. To ensure progression, resistance exercise programs were adjusted every third week based on new 1 RM testing
• Low Group
  • The LOW intervention involved an individualized, homebased walking program supported by a pedometer and one-on-one consultations (Supplementary Table 1). Participants were issued an Omron Walking Style Pro pedometer at baseline and were encouraged to progressively increase steps and ultimately to achieve 10,000 steps per day. Consultations were regularly held to discuss daily walking targets, and were encouraged to exercise and to integrate physical activity into activities of daily living.
• Outcome measures included interlimb volume % difference, L-Dex, self reported swelling. Muscular strength, breast cancer specific quality of life tool.
• In line with the hypothesis, they found similar point prevalent cases of BCRL between groups, as well as similar between group L-Dex scores and perceptions of heaviness, swelling and tightness post-intervention. While equivalence was not demonstrated in inter-arm volume % differences or self-reported pain, the negative deviations indicated reductions of these outcomes, favoring the HIGH group.
• Additionally, clinically relevant within group reductions in breast and arm symptoms were found in the HIGH group [40] at both 6 and 12 weeks.
• Participation in HIGH significantly improved upper-extremity strength with increases corresponding to 17%, 13%, and 7% at 6, 12, and 39 weeks, respectively, compared to 3% at all assessments in the LOW group.
• At 39 weeks follow-up, we found that the longer-term effect of the LOW and HIGH intervention was similar between groups or indicated reductions favoring the HIGH group for all outcomes.
• care should be taken when interpreting the 39-week follow-up results as no data regarding upper extremity resistance exercise behavior was collected postintervention, which is a limitation. Consequently, we cannot determine whether effects seen at 39 weeks were related to resistance exercise or other unknown factors.
• Limitations:
  • First, usual care in Denmark includes municipality lead rehabilitation programs and was therefore available for all participants. These programs are generally offered one to two times per week and include resistance exercise at low to moderate intensities. It is thus likely that a proportion of those in the LOW group also participated in resistance-based exercise at low to moderate loads during the intervention period. While there exists uncertainty as to the extent of this potential bias, the impact on findings would likely dilute differences between interventions.
  • In addition, though groups were statistically balanced at baseline, it should be noted that more participants in the LOW group had ALND and had been diagnosed with BCRL at baseline potentially swaying the results in favor of the HIGH group.
  • Further, in all 28% of the sample are missing inter-arm volume data due to body dimensions exceeding the DXA scan table, why caution in generalizing these findings to obese women is required. Future studies should be aware of this limitation and perform separate arm scans [44] as an alternative for these individuals.
  • Also, extracellular fluid measured by BIS was added to the test battery from participant 71 forward (54% of the sample). Therefore, complete data were not available for these two outcomes. Nonetheless, the comprehensive assessment of BCRL used in this study.
• In conclusion, novel findings from this study suggest that breast cancer survivors who are physically inactive before diagnosis benefit from and can safely participate in a multimodal intervention that includes supervised, heavy-load resistance exercise of the upper-extremities.