Journal of the Korea Academia-Industrial cooperation Society Vol. 17, No. 4 pp. 512-520, 2016 http://dx.doi.org/10.5762/kais.2016.17.4.512 ISSN 1975-4701 / eissn 2288-4688 여성유방암환자의림프부종감소와조절을위한운동의효과 : 체계적고찰과메타분석 김경희 1, 오기영 2* 1 가천대학교길병원진단검사의학과, 2 순천향대학교천안병원재활의학과 Exercise for reducing and controlling lymphedema in Women with breast cancer: A systematic review and meta-analysis Kyung-Hee Kim 1, Ki Young Oh 2* 1 Department of Laboratory medicine. Gachon University Gil Medical Center 2 Department of Physical medicine and rehabilitation. Soonchunhyang University Cheonan Hospital 요약유방암은여성에서가장흔한악성종양이며, 림프부종은가장흔한유방암수술후합병증가운데하나이다. 따라서림프부종과같은치료후유증의위험도감소와적절한관리는유방암생존환자와의사에게있어서그중요성이점차커지고있다. 이러한림프부종의발생을예방하기위하여흔히운동이처방된다. 그러나그러한운동의시기와효과에대해서는각각상반된결과들이보고되어왔다. 저자들은림프부종에대한운동효과를점검하여환자치료에최선의근거를도입하기위해최신문헌과상호심사된출판물, 전문기구의웹사이트를체계적으로고찰하여림프부종의예방이나치료를위해시행되는운동의효과를검토하였고, 그결과이미림프부종이발생해있는환자들에서는임상적인부종진행의차이점에유의성이없었지만, 발생전환자들에서는운동혹은훈련이이차성림프부종의발생을감소시키고진행을변경시키는양상을볼수있었다. 암치료의발전, 암과운동연구, 림프부종의관리를위해서는현재까지도출된근거들에대한고찰과이해가있어야임상의사들이적절한환자교육과전문가의뢰를시행할수있을것이다. Abstract Breast cancer is the most common malignancy in women, and lymphedema is one of the most common postoperative complications of breast surgery. Exercises are usually prescribed to prevent this occurrence. On the other hand, conflicting results regarding the effects and timing of such exercises have been reported. This study reviewed systematically the contemporary literature, peer-reviewed publications, and web sites of professional organizations that examined exercise for lymphedema prevention or therapy to determine the effects of exercise on lymphedema providing the best evidence for the treatment of patients. Exercise or training groups have strategies that appear to reduce the development of secondary lymphedema and altering its progression compared to the control group. Advances in cancer treatment, cancer and exercise research, and lymphedema management require physicians to have a basic understanding of the current evidence to provide the appropriate patient education and specialist referral. Keywords : Breast cancer, Exercise, Lymphedema 1. 서론 림프부종은림프계에서림프수송체계의불균형으로야기되는상태이며이러한교란의결과이환된신체부 위의피하조직에단백질이풍부한체액이축적되어부종이발생하게된다 [1]. 원발성림프부종은선천적이며매우드물게발생하며림프계의구조나기능부전으로인해해당신체부위에서 * Corresponding Author : Ki Young Oh(Soonchunhyang University Cheonan Hospital) Tel: +82-10-3347-7882 email: okokykkh@schmc.ac.kr Received February 11, 2016 Revised (1st March 4, 2016, 2nd March 28, 2016) Accepted April 7, 2016 Published April 30, 2016 512
여성유방암환자의림프부종감소와조절을위한운동의효과 : 체계적고찰과메타분석 필요로하는림프량을제공하지못하는것이특징이다 [2,3]. 보다흔히진단되는이차성림프부종은주로종양이나종양의치료로인한림프계의파괴혹은압박으로인해야기된다. 이차성림프부종의위험인자로는유방암의치료를위한액와림프절의수술적제거나액와방사선치료가있으며, 그결과팔, 손, 주변몸통사분역의부종이초래될수있다 [4]. 유방암연관림프부종 (breast cancer-related lymphedema, ) 의발생률은대략수술후 2년에약 26% 로추정된다 [4]. 따라서림프부종과같은치료후유증의위험도감소와적절한관리는유방암생존환자와의사에게있어서그중요성이점차커지고있다. 림프부종관리에유용한다양한조치로는팔운동, 수기림프배액, 압박의류나펌프사용등이있으며, 이중에서팔운동 (85%) 이가장흔히사용된다 [5]. 지난 20여년간암의예방과조절에있어운동의중요성이대두되어왔으나 [6,7], 액와림프절제나방사선치료를받은유방암생존환자에게있어상체운동은그리권장되지않았는데 [8], 이러한권고는상체운동이상지의림프부종을유발하거나악화시킨다는근거없는믿음에서기인하였다 [9,10]. 최근연구들은림프부종을가진여성이운동프로그램에참여하는것이팔부피나둘레에변화를야기하지않음을보여주었다 [11,12]. 그러나연구설계와측정방법의제한점으로인하여운동이림프계기능에미치는효과에대하여아직까지확고한결론이내려지지않고있다. 또한림프부종은다양한요인에기인하는것으로여겨지며정확한원인과병태생리가완전히이해되지않은상태이다 [13]. 림프부종의중증도에미치는운동의효과는논쟁의여지가있고변화기전이복잡하여환자들에게혼란을주고심리적으로가라앉게하여, 결과적으로일상적인운동처방의순응도에영향을미치게된다. 따라서저자들은림프부종에대한운동효과를시급히점검하여환자치료에최선의근거를도입하여야할필요성을절실히느껴그간의연구들을수집하고분류하여문헌연구를수행하게되었다. 2. 연구방법 2.1 연구설계각연구의중재들의정량적효과검토를수행하였고, 방법론의수준을위해모든관련된연구를평가하였다. 무작위대조시험 (randomized controlled trials, RCTs) 의내용과질에관련된요소보고는 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement를토대로하였다. 2.2 문헌검색방법문헌검색은영어출판논문으로데이터베이스검색은 Cumulative Index to Medline (1966-2014), EMBASE (1974-2014), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews (CDSR) 와 Google scholar를이용하였다. 검색엔진에사용한일반용어의예는다음과같다. 1. Lymphedema/ or elephantiasis/ 2. Lymphedema or elephantiasis 3. 1 or 2 4. exp Exercise/ 5. training/ 6. physical activity/ 7. exercise therapy/ 8. exp Sports/ 9. physical therapy 10. fitness/ 11. kinesiotherapy/ 12. exp Rehabilitation 13. 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 14. 3 and 13 데이터베이스검색후처음에잠재적으로관련된연구 1729개가확인되었으며중복된것을삭제하고 RCT 연구만을포함시킨후남은 103개의논문에대해추가적인고찰을시행하였다. 제목과초록을검토한결과 35개의연구가포함기준을만족하였고이들논문을상세히검사하였고 15개의연구논문이포함기준을충족하여최종검토대상으로하였다. 검토과정의흐름도는 [Fig. 1] 에제시하였다. 513
한국산학기술학회논문지제 17 권제 4 호, 2016 2.3 Inclusion criteria 임상적효과에대한가장강력한근거를제공하기위하여출판된 RCT 논문만을검토대상으로포함하였다. 다른포함기준으로는이고찰의목적을근거로하여, 유방암치료로액와림프절제술을받고수술후운동프로그램요법 ( 웨이트트레이닝, 유산소강화운동, 스트레칭과관절가동범위운동 ) 을시행한후연구결과평가를위해다음중한가지이상의검사를시행한여성으로하였다. 검사로는팔둘레와팔부피, 림프부종발생률, 혹은생체정기저항분광학검사 (bioimpedance spectroscopy, BIS) 가있다. 2.4 Exclusion criteria 남성을대상으로한연구는제외하였다. 수기림프배액, 압박옷이나피부치료를통해단지울혈제거요법만을다룬연구는이번고찰의초점인운동과림프부종의연관성이라는목적에적합하지않으므로제외하였다. 질평가와자료추출과정에서검토자간의의견불일치가있을경우에는상호동의에의해해결하였다. 2.5 자료추출및질평가자료추출도구로 Endnote 7 R 을사용하였다. 모든연구는 Cochrane Collaboration group 이개발한 the standard critical appraisal instrument for randomized studies를이용하여, 두명의독립적인검토자가면밀하게평가하였다. 2.6 자료분석충분한자료가확보된경우에는메타분석을시행하였다. 무작위대조시험 RCT 들을결합하는데는 Comprehensive Meta Analysis (CMA, Version 2.2) 소프트웨어를사용하였다. 발생률과같은이분척도자료에는교차비 (odds ratio, OR) 를 95% 신뢰구간 (confidence intervals, CI) 과함께표기하여치료영향을나타내었다. 부피, 둘레와같은동일한측정법으로얻어진연속자료에는 weighted mean difference (WMD) 를계산하여그결과를통계프로그램 (CMA) 을이용하여교차비 (OR) 로전환시켰다. 모든포인트추정값은연관된 95% CI와함께보고하였다. 비교대상이되는 RCT 결과들은비균질성을위한 random effects estimates, 95% CI, 카이제곱검정 (Chi 2 test) 기법과 I 2 통계를이용하여그결과들을혼합분석하였다. 3. 결과 3.1 대상연구들의요약분석한 15개의연구와각연구의자세한사항은표에나열하였다 (Table 1). 모든연구는액와림프절제술을포함한유방암수술을받은환자를대상으로한 RCT로서 2002년에서 2013년사이에출판되었다. 모든연구에서연구참가자들은개입 ( 중재 ) 군이나대조군에무작위로할당되었고각군의수는거의동일하였으며, 기초적특성은중재군과대조군사이에잘일치되었다. 3.2 Risk of bias in included studies 바이어스위험도는두명의저자가독립적으로판단하였다. 요약과바이어스위험도표는 [Fig. 2] 와 [Fig. 3] 에나타내었다. 3.3 림프부종중증도감소에대한운동의효과림프부종이이미발생한환자들에서운동군과대조군사이에차이가있음을보고한연구들이있다. 예로써, Heyes 2008, Johansson 2013, Cormie 2013 는 BIS 비율을검사하였고, Kim 2010 과 Cormie 2013 는이환부부피의변화를, Schmits 2009와 Jeff 2012는부피의차이를지수 (index) 로하여운동효과를조사하였다. 이런모든연구들은운동선호경향을보였으나결과에통계학적유의성은결여되어있었다 [Fig. 4, 5, and 6]. 3.4 림프부종발생률감소에대한운동의효과유방암관련림프부종발생률의차이는세개의연구에보고되어있었다 (Box 2002; Lacomba 2010; Kilbreath 2012). 합산된자료는운동치료군에비교하여대조군에서통계적으로유의하게높은림프부종발생률을보여주고있 514
여성유방암환자의림프부종감소와조절을위한운동의효과 : 체계적고찰과메타분석 다 (OR: 0.260; 95% CI: 0.118 ~ 0.574) [Fig. 7]. 그외에림프부종의발생률과비슷한지수들을이용하여보고한연구가여섯개있었다. Bendz 2002와 Courneya 2007는이환부의부피차이를검사하였고, Beurskens 2007와 Roger 2011는부피변화를보고하였으며, Sandel 2005와 Ahmed 2006는이환부의둘레변화를밝혀냈다. 이연구들의자료는운동선호경향을보였으나결과에여전히통계적유의성은보이지않았다 [Fig. 8, 9, 10]. 4. 고찰유방암연관림프부종은많은생존자들에게계속큰문제거리로남아있다. 이번의체계적검토를통해, 유방암환자군에있어서운동연구의대부분은지속적으로림프부종발생의위험도를다루어오고있음을확인하였다. 림프부종이발생할위험성은유방암생존자의여생을통하여지속되며, 발생률의범위는유방암진단후 2년에 13% [14], 10-40 개월에 17% [15], 18 개월에 30% [16], 2-6년에 17% [17] 등으로보고되고있다. 유방암외에는림프부종을동반하거나발생위험을가진다른환자군에서의운동중재에관한문헌은제한적이다. 4.1 암진단후운동의유익암생존자에대한운동의다양한이득이보고되어있다. 암생존자에대한운동지침인 The 2010 American College of Sports Medicine (ACSM) Exercise Guidelines for Cancer Survivors에서는 암생존자들이당면하는심리적그리고생리적시험의일부는운동을통하여예방, 약화, 치료또는재활할수있다 고명시하였다 [18]. 이러한운동의이득에는유연성증가, 피로감소, 강도힘세기의증가, 신체상과삶의질향상, 신체조성개선그리고불안감소가포함된다. 더욱이 ACSM 지침은운동이암의재발이나이차암발생위험성을감소시키는것과도연관된다고인용하고있다. 암치료과정에서의운동효과에대한추가적인두개의문헌고찰역시운동이생리적, 심리적이득을제시하 는것으로결론내렸다 [19, 20]. 림프부종의위험이있거나이전에림프부종으로진단되었던경험이있는환자에서운동의효과는최근까지도논쟁의여지가있다. 하지만운동은근골격계의펌프기전의활성화로정맥혈과림프액의환류를증가시키는등실제적으로림프부종의위험성에있어서팔다리에생리적이점을많이부여해준다 [21, 22]. 게다가상체운동은림프관에대한교감신경계의구동을재설정함으로써장기적으로림프부종의관리에보조적역할을수행할수있는것으로가정된다 [22]. 4.2 운동의림프부종예방효과이번체계적검토에서는유방암후림프부종발생율을보고한연구들에서, 운동치료군은대조군에비교하여발병률이낮은것으로드러났으며, 발병률과유사한다른지표들을이용한비슷한연구들역시비록통계적유의성은없었으나운동치료가선호되는경향을보였다.[23-25] 4.3 기존의림프부종을가진환자에대한운동의효과이미림프부종이발생해있는환자에서진행의차이점을보고한연구들에서는주로 BIS ratio, 이환부팔의부피변화, 혹은양팔의부피차이를관찰함으로써운동의효과를조사하였었는데, 예방효과와는달리운동을시행한군은림프부종의진행이덜한것처럼보이기는하였지만메타분석결과로는통계적유의성은없었다.[26-31] 4.4 제한점본체계적고찰은 1966년에서 2014년까지영어로출판된상호심사논문만을대상으로한한계가있다. 게다가많은연구가각연구방법과결과의이질성과다양성으로인해메타분석에서결합되지못하였다. 515
한국산학기술학회논문지제 17 권제 4 호, 2016 Fig. 3. Summary of the sources of bias for the studies included in this review Fig. 1. Literature review process for exercise and lymphedema systematic review Fig. 4. Comparison of exercise versus control in with BIS ratio as the study outcome. Fig. 5. Comparison of exercise versus control in with volume change as the study outcome. Fig. 6. Comparison of exercise versus control in with volume difference as the study outcome. Fig. 2. Summary of the study authors' review on the sources of bias for each included study 516
여성유방암환자의림프부종감소와조절을위한운동의효과 : 체계적고찰과메타분석 Fig. 7. Comparison of exercise versus control in with lymphedema incidence as study outcome. Fig. 8. Comparison of exercise versus control in BRCL with volume change as the study outcome. Table 1. Summary of the RCTs included in the review Author Participants Sample size (Intervention+Co ntrol) Roger T(2011) stagei~iii 52+52 18-month armvolume change Outcomes Intervention Results Exercise: aerobic warm up, walking, resistance exercise, stretching (RESTOREprogram)-6months Intervention: 33.5 ml Control:60.4ml(p=0.56) Sandel(2005) 19+19 13-and 26-week armcircumferencechange Exercise: aerobic warm up, core exercise, dance movement wrapup 12weeks Intervention: 120.1 cm 120.1 cm Control:112.8cm 113.6cm Kim(2010) 20+20 8-week armvolumechange Exercise: Remedial exercise + resistive exercise 8 weeks Control:Remedialexercise Intervention: 4987 cc 4012 cc Control:4744cc 4036cc Lacomba(2010) 59+57 12-month lymphedemaincidence changeinvolumeratio maximumcircumferencechange Exercise: Resistive exercise + stretching exercise + PNF exercise 9 weeks Control:onlyeducation Intervention: volume increase 1.6% /0.68 cm Control: volume increase 5.1% /1.15 cm incidenceor=0.22 Courneya(2007) stagei~iiia undergoingadjuva ntchemotherapy 78+82+82 Median 17-week LEincidence; Armvolumedifference Resistive exercise: 60~70% of 1RM Aerobicexercise:60%ofVO2max Control:noexercise(median17week) Resistive exercise: -9 ml, 3/82 (3.7%) Aerobicexercise:-4mL,7/78(9.0%) Control:-5mL6/82(7.3%) Bendz(2002) 101+104 6-month, 2-year LEincidence; Armvolumedifference Early exercise: start at pod 1 Delayedexercise:startatpod14 Early exercise: 102.3 ml/103.7 ml, 5%/13% Delayedexercise:103.0mL/104.5mL, 4%/12% Hayes(2008) 16+16 12-week, 24-week bioimpedancespectroscopy(ratio) perometry(volumedifference) Exercise: aerobic exercise + resistive exercise 12 weeks Intervention BIS=-0.01/0.02 volume=13/2 ControlBIS=0.00/0.01volume=43/19 Cormie(2013) 22+21+19 3-month bioimpedancespectroscopy(ratio) armvolumechange armcircumferencechange High load resistive exercise: 75-85% of 1RM Lowloadresistiveexercise:55-65% of1rm Control:noexercise (3 months) High load resistive exercise BIS: -0.2 volume: -53.5 circumference: -0.9 Lowloadresistiveexercise BIS: -1.6 volume: 98.5 circumference: 0.3 Control BIS: -0.9 volume: 1.6 circumference: -1.7 517
한국산학기술학회논문지제 17 권제 4 호, 2016 Box(2002) 32+33 6-, 12-, 24-month LE incidence Treatment group: part of PMCP Treatment group volume: by bioimpedancespectroscopy(ratio,% change), armvolumechange, armcircumferencechange Controlgroup:monitoring 1,2,3/32 circumference: 1,1,3/32 MFBIA ratio: 2,4,2/32 MFBIA change: 2,4,3/32 Controlgroup volume: 5,4,9/33 circumference: 1,1,4/33 MFBIA ratio: 3,2,5/33 MFBIA change: 3,4,5/33 Jeffs (2012) 11+12 12 weeks, 26 weeks perometry(elv,%elv) Exercise: home exercise program(gravity resistive exercise, hand pumping) 26 weeks Intervention ELV=-39.0/-58.0 %ELV=-8.08/-10.53 Control ELV=-22.5/-64.0 %ELV=-2.83/-9.20 Ahmed (2006) 23+22 6-month lymphedema incidence by arm circumference change Intervention: weight training 6 months Intervention 31.18/30.84 31.73/31.24 Control30.79/29.23 30.83/30.61 Beurskens (2007) 15+15 3-, 6-month armvolumechange Intervention: strengthening exercise and general conditioning 3 months Control:leafletflyerwithadvice Intervention 255 261 268 Control259 263 272 Kilbreath (2012) 81+79 8-week, 6-month lymphedema incidence by bioimpedancespectroscopy(ratio),in terlimbvolumedifference interlimbcircumferencechange Intervention: strengthening exercise and stretching exercise - 8 weeks Intervention BIS: 5(7)-6(8) volume: 8(11)-6(8) circumference: 6(8)-5(7) Control BIS:11(15)-9(13) volume: 8(10)-9(13) circumference: 5(5)-4(6) Johansson K(2013) chronic 15+14 8-week bioimpedancespectroscopy(ratio) interlimbvolumedifference localtissuewater Intervention: water based Intervention BIS: 1.13 1.13 exercise(swimming and shoulder volume: 21.3 21.4 TDC: exercise) - 8 weeks 28.0 28.0 Control:samewayastheyhaddone Control BIS: 1.22 1.22 volume: 21.6 21.0 TDC: 26.1 27.4 Schmitz (2009) 71+70 12-month interlimbvolumedifference Intervention: weight lifting exercise stretching exercise) - 12 months Control:samewayastheyhaddone Intervention : -0.69% Control:-0.98% Fig. 9. Comparison of exercise versus control in BRCL with lymphedema incidence as study outcome. Fig. 10. Comparison of exercise versus control in BRCL with circumference change as study outcome. 518
여성유방암환자의림프부종감소와조절을위한운동의효과 : 체계적고찰과메타분석 5. 결론 이번의림프부종예방및치료에대한운동의효과에대한근거를알아보고자했던문헌고찰에서유방암후림프부종발생율을보면, 운동치료군은대조군에비교하여발병률이낮은것으로드러났으며, 이미림프부종이발생해있는환자들에서진행의차이점을보면통계적유의성은없었지만운동치료군은림프부종의진행이덜한양상을보였다. 많은연구들이있었지만, 각연구방법과결과의이질성과다양성으로인해메타분석에서결합되지못하는등한계점이나타나편향을좀더최소화하고최적의치료법을찾아낼수있는연구디자인을갖춘림프부종의관리에관한추가적인연구가필요한실정이며, 림프부종관리에대한운동처방평가를위해운동빈도, 기간, 방식, 강도, 진행전략등포괄적인정보가필요할것이다. 향후의연구는림프배액에가장큰효과를줄수있는운동을찾아내고, 암치료의각단계마다에서효능을평가할수있어야할것이고, 그렇게함으로써, 이차성림프부종의예방, 회복, 관리에대한운동의기여뿐만아니라암생존자들의건강과웰빙에대한운동의장기적인효과를조사하는전향적연구에도움이되리라생각된다. References [1] J. M. Armer, The problem of post-breast cancer lymphedema: impact and measurement issues, Cancer Invest, Vol.23, pp.76 83, 2005. DOI: http://dx.doi.org/10.1081/cnv-48707 [2] C. A. Harwood, P. S. Mortimer, Causes and clinical manifestations of lymphatic failure, Clin Dermatol, Vol.13, pp.459 471, 1995. DOI: http://dx.doi.org/10.1016/0738-081x(95)00096-x [3] P. S. Mortimer, The pathophysiology of lymphedema. Cancer, Vol.83(12 Suppl American), pp.2798 2802, 1998. [4] V. S. Erickson, M. L. Pearson, P. A. Ganz, J. AdamsJ, K. L. Kahn, Arm edema in breast cancer patients, J Natl Cancer Inst, Vol.93, pp.96 111, 2001. DOI: http://dx.doi.org/10.1093/jnci/93.2.96 [5] Y. M. Lee, S. S. Mak, S. M. Tse, S. J. Chan, Lymphoedema care of breast cancer patients in a breast care clinic: a survey of knowledge and health practice, Support Care Cancer, Vol.9, pp.634 641, 2001. DOI: http://dx.doi.org/10.1007/s005200100270 [6] C. Doyl, L. H. Kushi, T. Byers, K. S. Courneya, W. D. Wahnefried, B. Grant, et al, Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices, CA Cancer J Clin, Vol.56, pp.323 353, 2006. DOI: http://dx.doi.org/10.3322/canjclin.56.6.323 [7] World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC, AICR, 2007. [8] B. Cheema, C. A. Gaul, K. Lane, M. A. Fiatarone Singh. Progressive resistance training in breast cancer: a systematic review of clinical trials, Breast Cancer Res Treat, Vol.109, pp.9 26, 2008. DOI: http://dx.doi.org/10.1007/s10549-007-9638-0 [9] P. A. Ganz, The quality of life after breast cancer solving the problem of lymphedema, N Engl J Med, Vol.340, pp.383 385. 1999. DOI: http://dx.doi.org/10.1056/nejm199902043400511 [10] S. G. Rockson, Precipitating factors in lymphedema: myths and realities, Cancer, Vol.83(12 Suppl American), pp.2814 2816, 1998. [11] D. C. McKenzie, Abreast in a boat a race against breast cancer, CMAJ, Vol.159, pp.376 378, 1998. [12] S. R. Harris, S. L. Niesen-Vertommen, Challenging the myth of exercise-induced lymphoedema following breast cancer: a series of case report, J Surg Oncol, Vol.74, pp.95 99, 2001. DOI:http://dx.doi.org/10.1002/1096-9098(200006)74:2< 95:: AID-JSO3>3.0.CO;2-Q [13] K. Lane, D. Worsley, D. McKenzie, Exercise and the lymphatic system: implication for breast-cancer survivors, Sports Med, Vol.35, pp.461 471, 2005. DOI: http://dx.doi.org/10.2165/00007256-200535060-00001 [14] A. Sagen, R. Karesen, M. A. Risberg, Physical activity for the affected limb and arm lymphedema after breast cancer surgery: A prospective, randomized controlled trial with two years follow-up, Acta Oncol, Vol.48, pp.1102 1110, 2009. DOI: http://dx.doi.org/10.3109/02841860903061683 [15] R. L. Ahmed, W. Thomas, D. Yee, K. H. Schmitz, Randomized controlled trial of weight training and lymphedema in breast cancer survivors, J Clin Oncol. Vol.24, pp.2765 2772, 2006. DOI: http://dx.doi.org/10.1200/jco.2005.03.6749 [16] S. C. Hayes, H. R. Hirche, J. Turner, Exercise and secondary lymphedema: safety, potential benefits, and research issues, Med Sci Sports Exerc, Vol.41, pp.483 489, 2009. DOI: http://dx.doi.org/10.1249/mss.0b013e31818b98fb [17] K. H. Schmitz, R. L. Ahmed, A. B. Troxel, A. Cheville, L. L. Grant, R. Smith, et al, Weight lifting for women at risk for breast cancerrelated lymphedema: a randomized trial, JAMA, Vol.304, pp.2699 2705, 2010. DOI: http://dx.doi.org/10.1001/jama.2010.1837 [18] K. H. Schmitz, K. S. Courneya, C. Matthews, W. D. Wahnefried, D. A. Galvao, B. M. Pinto, et al, American College of Sports Medicine roundtable on exercise guidelines for cancer survivors, Med Sci Sports Exerc, Vol.42, pp.1409 1426, 2010. DOI: http://dx.doi.org/10.1249/mss.0b013e3181e0c112 519
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