A randomized study to prevent lymphedema in women treated for breast cancer: CALGB 70305 (Alliance)

Electra D. Paskett; Jennifer Le-Rademacher; Jill M. Oliveri; Heshan Liu; Drew K. Seisler; Jeffrey A. Sloan; Jane M. Armer; Michelle J. Naughton; Karen Hock; Michael Schwartz; Gary Unzeitig; Marianne Melnik; Lisa D. Yee; Gini F. Fleming; John R. Taylor; Charles Loprinzi

doi:10.1002/cncr.33183

A randomized study to prevent lymphedema in women treated for breast cancer: CALGB 70305 (Alliance)

Electra D. Paskett, Jennifer Le-Rademacher, Jill M. Oliveri, Heshan Liu, Drew K. Seisler, Jeffrey A. Sloan, Jane M. Armer, Michelle J. Naughton, Karen Hock, Michael Schwartz, Gary Unzeitig, Marianne Melnik, Lisa D. Yee, Gini F. Fleming, John R. Taylor, Charles Loprinzi

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education-only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group-randomized trial across 38 cooperative group sites. Methods: The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self-reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a ≥10% difference in limb volume at any time post-surgery up to 18 months after surgery or diagnosis by a health provider. Cochran-Mantel-Haenszel tests were used to compare lymphedema-free rates between groups, stratified by lymph node surgery type. Self-reported ROM differences were compared between groups. Results: A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema-free rates were 58% (EO) versus 55% (LEAP) (P =.37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one-third wore a sleeve ≥75% of the time; 50% performed lymphedema exercises at least weekly. Conclusion: Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.

Original language	English (US)
Pages (from-to)	291-299
Number of pages	9
Journal	Cancer
Volume	127
Issue number	2
DOIs	https://doi.org/10.1002/cncr.33183
State	Published - Jan 15 2021

Keywords

breast cancer
education
exercise
lymphedema
prevention
range of motion

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1002/cncr.33183

Cite this

Paskett, E. D., Le-Rademacher, J., Oliveri, J. M., Liu, H., Seisler, D. K., Sloan, J. A., Armer, J. M., Naughton, M. J., Hock, K., Schwartz, M., Unzeitig, G., Melnik, M., Yee, L. D., Fleming, G. F., Taylor, J. R., & Loprinzi, C. (2021). A randomized study to prevent lymphedema in women treated for breast cancer: CALGB 70305 (Alliance). Cancer, 127(2), 291-299. https://doi.org/10.1002/cncr.33183

Paskett, ED, Le-Rademacher, J, Oliveri, JM, Liu, H, Seisler, DK, Sloan, JA, Armer, JM, Naughton, MJ, Hock, K, Schwartz, M, Unzeitig, G, Melnik, M, Yee, LD, Fleming, GF, Taylor, JR & Loprinzi, C 2021, 'A randomized study to prevent lymphedema in women treated for breast cancer: CALGB 70305 (Alliance)', Cancer, vol. 127, no. 2, pp. 291-299. https://doi.org/10.1002/cncr.33183

@article{4bcf504d85bd4fdb96d757e5fc6a4520,

title = "A randomized study to prevent lymphedema in women treated for breast cancer: CALGB 70305 (Alliance)",

abstract = "Background: Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education-only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group-randomized trial across 38 cooperative group sites. Methods: The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self-reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a ≥10% difference in limb volume at any time post-surgery up to 18 months after surgery or diagnosis by a health provider. Cochran-Mantel-Haenszel tests were used to compare lymphedema-free rates between groups, stratified by lymph node surgery type. Self-reported ROM differences were compared between groups. Results: A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema-free rates were 58% (EO) versus 55% (LEAP) (P =.37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one-third wore a sleeve ≥75% of the time; 50% performed lymphedema exercises at least weekly. Conclusion: Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.",

keywords = "breast cancer, education, exercise, lymphedema, prevention, range of motion",

author = "Paskett, {Electra D.} and Jennifer Le-Rademacher and Oliveri, {Jill M.} and Heshan Liu and Seisler, {Drew K.} and Sloan, {Jeffrey A.} and Armer, {Jane M.} and Naughton, {Michelle J.} and Karen Hock and Michael Schwartz and Gary Unzeitig and Marianne Melnik and Yee, {Lisa D.} and Fleming, {Gini F.} and Taylor, {John R.} and Charles Loprinzi",

note = "Funding Information: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), UG1CA189817, UG1CA189819, U10CA180790, U10CA180836, U10CA180850, and UL1TR001409; Susan G. Komen for the Cure (POP0600316); the Lance Armstrong Foundation (66426); and a private donor. Funding Information: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), UG1CA189817, UG1CA189819, U10CA180790, U10CA180836, U10CA180850, and UL1TR001409; Susan G. Komen for the Cure (POP0600316); the Lance Armstrong Foundation (66426); and a private donor. The study was designed as a randomized phase 3 trial within Cancer and Leukemia Group B (CALGB, now Alliance [CALGB 70305]). The eligibility process used a 2-step procedure, meaning eligible participants were enrolled in step 1 and then registered for step 2 if they had either ALND or sentinel lymph node dissection (SLND). Women aged ?18 years who were newly diagnosed with breast cancer (stage I-III) and had no history of lymphedema, lobular or ductal carcinoma in situ, or invasive breast cancer were eligible. Patients who received neoadjuvant chemotherapy were eligible if presurgery arm measurements were completed prior to first chemotherapy treatment. Eligible patients had medical clearance to participate in a mild exercise program and had an upper arm size that accommodated a standard-size elastic compression sleeve and gauntlet. Patients who underwent bilateral mastectomies, bilateral ALND, and/or bilateral radiation were ineligible, but those who had immediate or delayed reconstruction were eligible. Patients were recruited from 38 CALGB and National Cancer Institute clinical trials cooperative group sites across the United States from December 2006 to September 2013, with follow-up until December 2015. Eligible sites were providing no more than lymphedema prevention education to patients before being randomly assigned to intervention groups of education only (EO) or lymphedema education and prevention (LEAP) for focused education plus exercise (including sleeve use). A stratified permuted block approach (stratified by the annual number of stage I-III breast cancer patients treated at the institution) was used for randomization. Participating institutions were randomized to EO or LEAP so that all participants at an institution received identical treatment plans to minimize contamination bias. The trial was approved by the institutional review board (IRB) of each of the participating sites, and participants signed IRB-approved, protocol-specific informed consent forms in accordance with federal and institutional guidelines. The study was designed as a randomized phase 3 trial within Cancer and Leukemia Group B (CALGB, now Alliance [CALGB 70305]). The eligibility process used a 2-step procedure, meaning eligible participants were enrolled in step 1 and then registered for step 2 if they had either ALND or sentinel lymph node dissection (SLND). Women aged ?18 years who were newly diagnosed with breast cancer (stage I-III) and had no history of lymphedema, lobular or ductal carcinoma in situ, or invasive breast cancer were eligible. Patients who received neoadjuvant chemotherapy were eligible if presurgery arm measurements were completed prior to first chemotherapy treatment. Eligible patients had medical clearance to participate in a mild exercise program and had an upper arm size that accommodated a standard-size elastic compression sleeve and gauntlet. Patients who underwent bilateral mastectomies, bilateral ALND, and/or bilateral radiation were ineligible, but those who had immediate or delayed reconstruction were eligible. Patients were recruited from 38 CALGB and National Cancer Institute clinical trials cooperative group sites across the United States from December 2006 to September 2013, with follow-up until December 2015. Eligible sites were providing no more than lymphedema prevention education to patients before being randomly assigned to intervention groups of education only (EO) or lymphedema education and prevention (LEAP) for focused education plus exercise (including sleeve use). A stratified permuted block approach (stratified by the annual number of stage I-III breast cancer patients treated at the institution) was used for randomization. Participating institutions were randomized to EO or LEAP so that all participants at an institution received identical treatment plans to minimize contamination bias. The trial was approved by the institutional review board (IRB) of each of the participating sites, and participants signed IRB-approved, protocol-specific informed consent forms in accordance with federal and institutional guidelines. Participants were recruited at their first preoperative visit, consented and registered to Step 1. Baseline measurements of height, weight, self-reported ROM, and arm circumference18 were taken by trained nurses before treatment. Participants completed questionnaires regarding demographics, lymphedema knowledge, body image, self-efficacy,19 fear of cancer recurrence, self-reported pain and swelling, self-reported ROM, health-related QOL,20 and adherence to lymphedema risk-reduction practices. Assessments were repeated after surgery and at 6 (by mail), 12, and 18 months after surgery. All eligible participants were registered to step 2 ?6 weeks after surgery. A trained lymphedema prevention educator reviewed lymphedema etiology, signs, symptoms, treatments, and preventative self-care practices (Table 1). Participants at LEAP institutions also received an intervention of assessment and instruction by a physical therapist in an individualized exercise regimen involving breathing, stretching, strengthening, and personalized ROM exercises; all patients were taught the same exercises. Participants successfully demonstrated study exercises and were instructed to perform exercises daily, provided an instructional video for home use, and asked to document exercise performance in study calendars. On average, these activities required approximately 15 min/d to complete. LEAP participants also received 2-pound (0.91-kg) hand weights for daily use and an elastic compression sleeve and gauntlet (Juzo class I 20-30 mm Hg) to wear during exercise (study-related or personal), air travel, and/or vigorous activity. Participants met with the study educator for a brief visit at 12 and 18 months postsurgery and by phone at 9 and 15 months postsurgery to answer questions and to reinforce adherence to study interventions. Abbreviations: ACS, American Cancer Society; LEAP, lymphedema education and prevention; QOL, quality of life. The primary endpoint of this trial was lymphedema-free rates at 18 months. Lymphedema was defined as an increase of ?10% in the volume of the affected arm between the preoperative and 12- or 18-month visits, after controlling for percentage change in BMI, or as a diagnosis by a participant's physician (using his/her own clinical judgment) any time following the postoperative assessment (up to 18 months postsurgery).21,22 While there is no ?gold standard? definition for lymphedema, ?10% limb volume change is a conservative and commonly used definition.23 Secondary outcomes included 1) severity of lymphedema defined as change in arm circumference at the site of greatest difference, 2) self-reported ROM, and 3) adherence to sleeve/gauntlet use and exercises (LEAP group). All analyses accounted for cluster (site) randomization as specified in the protocol. The primary study objective was to compare lymphedema-free rates between groups. The study was designed to detect an improvement in the 18-month lymphedema-free rate from 65% (EO group) to 77% (LEAP group). A total of 560 participants provided 81% power with a 1-sided type I error of 0.05 using the method described by Donner and Klar24 to account for the group-randomized design, assuming an intracluster correlation (ICC) of 0.02, based on estimates of rates of lymphedema provided by Alliance institutions as well as from CALGB 79804. The primary intent-to-treat analysis (ITT) included all eligible participants. Participants with missing lymphedema measurements at 12- and/or 18-months post-surgery and whose lymphedema status could not be determined were classified as not lymphedema-free. Lymphedema-free rates were adjusted for BMI at 18 months postsurgery, stratified by type of lymph node dissection and institution size (small, ? 275 new breast cancer patients annually; moderate, 276 to 450 new breast cancer patients annually; and large, ?450 new breast cancer patients annually), and compared between the 2 groups using an adjusted Cochran-Mantel-Haenszel test to account for ICC.25 Sensitivity analyses using complete case and simple and multiple imputations for missing data were conducted and confirmed original results. Imputation-based models produced similar findings. The difference in arm circumference from baseline to 12 and 18 months post-surgery at the site of the greatest difference was summarized and compared using the generalized estimating equation (GEE) model to account for cluster randomization. Self-reported ROM was assessed by participants choosing 1 of 6 illustrations best indicating how high they could reach above their head with each arm. Responses were dichotomized to reflect full ROM versus not full ROM. ROM differences were compared between study groups before surgery versus 12 and 18 months after surgery using GEE models to account for cluster randomization. Each arm was assessed independently, adjusting for baseline BMI, surgery type, type of lymph node dissection, affected arm being dominant, and receipt of radiation and/or chemotherapy. Analyses of these secondary endpoints were limited to complete cases. At 12 and 18 months, LEAP group participants were assessed for adherence to performing individualized arm exercises and wearing an elastic sleeve at least 75% of the time during heavy arm use, exercise, or travel. Statistical analyses concerning adherence were descriptive. Data collection and statistical analyses were conducted by the Alliance Statistics and Data Center. All analyses were completed on the study database frozen on April 30, 2016. Data quality was ensured by review of data by the Alliance Statistics and Data Center and by the study chairperson following Alliance policies. The trial was monitored at least twice annually by the Alliance Data and Safety Monitoring Committee. All analyses were conducted using SAS software version 9.4. Funding Information: Electra D. Paskett has received grants from Merck Foundation and Pfizer. Gini F. Fleming has been the principal investigator of an industry‐sponsored trial for Corcept, Abbvie/Tesaro, Roche/Genentech, Syndax, 47 Inc, Iovance, Syros, and Eisai. The other authors made no disclosures. Charles Loprinzi reported grants from NCI during the conduct of this study as indicated on his ICMJE form. Publisher Copyright: {\textcopyright} 2020 American Cancer Society",

year = "2021",

month = jan,

day = "15",

doi = "10.1002/cncr.33183",

language = "English (US)",

volume = "127",

pages = "291--299",

journal = "Cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "2",

}

TY - JOUR

T1 - A randomized study to prevent lymphedema in women treated for breast cancer

T2 - CALGB 70305 (Alliance)

AU - Paskett, Electra D.

AU - Le-Rademacher, Jennifer

AU - Oliveri, Jill M.

AU - Liu, Heshan

AU - Seisler, Drew K.

AU - Sloan, Jeffrey A.

AU - Armer, Jane M.

AU - Naughton, Michelle J.

AU - Hock, Karen

AU - Schwartz, Michael

AU - Unzeitig, Gary

AU - Melnik, Marianne

AU - Yee, Lisa D.

AU - Fleming, Gini F.

AU - Taylor, John R.

AU - Loprinzi, Charles

N1 - Funding Information: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), UG1CA189817, UG1CA189819, U10CA180790, U10CA180836, U10CA180850, and UL1TR001409; Susan G. Komen for the Cure (POP0600316); the Lance Armstrong Foundation (66426); and a private donor. Funding Information: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), UG1CA189817, UG1CA189819, U10CA180790, U10CA180836, U10CA180850, and UL1TR001409; Susan G. Komen for the Cure (POP0600316); the Lance Armstrong Foundation (66426); and a private donor. The study was designed as a randomized phase 3 trial within Cancer and Leukemia Group B (CALGB, now Alliance [CALGB 70305]). The eligibility process used a 2-step procedure, meaning eligible participants were enrolled in step 1 and then registered for step 2 if they had either ALND or sentinel lymph node dissection (SLND). Women aged ?18 years who were newly diagnosed with breast cancer (stage I-III) and had no history of lymphedema, lobular or ductal carcinoma in situ, or invasive breast cancer were eligible. Patients who received neoadjuvant chemotherapy were eligible if presurgery arm measurements were completed prior to first chemotherapy treatment. Eligible patients had medical clearance to participate in a mild exercise program and had an upper arm size that accommodated a standard-size elastic compression sleeve and gauntlet. Patients who underwent bilateral mastectomies, bilateral ALND, and/or bilateral radiation were ineligible, but those who had immediate or delayed reconstruction were eligible. Patients were recruited from 38 CALGB and National Cancer Institute clinical trials cooperative group sites across the United States from December 2006 to September 2013, with follow-up until December 2015. Eligible sites were providing no more than lymphedema prevention education to patients before being randomly assigned to intervention groups of education only (EO) or lymphedema education and prevention (LEAP) for focused education plus exercise (including sleeve use). A stratified permuted block approach (stratified by the annual number of stage I-III breast cancer patients treated at the institution) was used for randomization. Participating institutions were randomized to EO or LEAP so that all participants at an institution received identical treatment plans to minimize contamination bias. The trial was approved by the institutional review board (IRB) of each of the participating sites, and participants signed IRB-approved, protocol-specific informed consent forms in accordance with federal and institutional guidelines. The study was designed as a randomized phase 3 trial within Cancer and Leukemia Group B (CALGB, now Alliance [CALGB 70305]). The eligibility process used a 2-step procedure, meaning eligible participants were enrolled in step 1 and then registered for step 2 if they had either ALND or sentinel lymph node dissection (SLND). Women aged ?18 years who were newly diagnosed with breast cancer (stage I-III) and had no history of lymphedema, lobular or ductal carcinoma in situ, or invasive breast cancer were eligible. Patients who received neoadjuvant chemotherapy were eligible if presurgery arm measurements were completed prior to first chemotherapy treatment. Eligible patients had medical clearance to participate in a mild exercise program and had an upper arm size that accommodated a standard-size elastic compression sleeve and gauntlet. Patients who underwent bilateral mastectomies, bilateral ALND, and/or bilateral radiation were ineligible, but those who had immediate or delayed reconstruction were eligible. Patients were recruited from 38 CALGB and National Cancer Institute clinical trials cooperative group sites across the United States from December 2006 to September 2013, with follow-up until December 2015. Eligible sites were providing no more than lymphedema prevention education to patients before being randomly assigned to intervention groups of education only (EO) or lymphedema education and prevention (LEAP) for focused education plus exercise (including sleeve use). A stratified permuted block approach (stratified by the annual number of stage I-III breast cancer patients treated at the institution) was used for randomization. Participating institutions were randomized to EO or LEAP so that all participants at an institution received identical treatment plans to minimize contamination bias. The trial was approved by the institutional review board (IRB) of each of the participating sites, and participants signed IRB-approved, protocol-specific informed consent forms in accordance with federal and institutional guidelines. Participants were recruited at their first preoperative visit, consented and registered to Step 1. Baseline measurements of height, weight, self-reported ROM, and arm circumference18 were taken by trained nurses before treatment. Participants completed questionnaires regarding demographics, lymphedema knowledge, body image, self-efficacy,19 fear of cancer recurrence, self-reported pain and swelling, self-reported ROM, health-related QOL,20 and adherence to lymphedema risk-reduction practices. Assessments were repeated after surgery and at 6 (by mail), 12, and 18 months after surgery. All eligible participants were registered to step 2 ?6 weeks after surgery. A trained lymphedema prevention educator reviewed lymphedema etiology, signs, symptoms, treatments, and preventative self-care practices (Table 1). Participants at LEAP institutions also received an intervention of assessment and instruction by a physical therapist in an individualized exercise regimen involving breathing, stretching, strengthening, and personalized ROM exercises; all patients were taught the same exercises. Participants successfully demonstrated study exercises and were instructed to perform exercises daily, provided an instructional video for home use, and asked to document exercise performance in study calendars. On average, these activities required approximately 15 min/d to complete. LEAP participants also received 2-pound (0.91-kg) hand weights for daily use and an elastic compression sleeve and gauntlet (Juzo class I 20-30 mm Hg) to wear during exercise (study-related or personal), air travel, and/or vigorous activity. Participants met with the study educator for a brief visit at 12 and 18 months postsurgery and by phone at 9 and 15 months postsurgery to answer questions and to reinforce adherence to study interventions. Abbreviations: ACS, American Cancer Society; LEAP, lymphedema education and prevention; QOL, quality of life. The primary endpoint of this trial was lymphedema-free rates at 18 months. Lymphedema was defined as an increase of ?10% in the volume of the affected arm between the preoperative and 12- or 18-month visits, after controlling for percentage change in BMI, or as a diagnosis by a participant's physician (using his/her own clinical judgment) any time following the postoperative assessment (up to 18 months postsurgery).21,22 While there is no ?gold standard? definition for lymphedema, ?10% limb volume change is a conservative and commonly used definition.23 Secondary outcomes included 1) severity of lymphedema defined as change in arm circumference at the site of greatest difference, 2) self-reported ROM, and 3) adherence to sleeve/gauntlet use and exercises (LEAP group). All analyses accounted for cluster (site) randomization as specified in the protocol. The primary study objective was to compare lymphedema-free rates between groups. The study was designed to detect an improvement in the 18-month lymphedema-free rate from 65% (EO group) to 77% (LEAP group). A total of 560 participants provided 81% power with a 1-sided type I error of 0.05 using the method described by Donner and Klar24 to account for the group-randomized design, assuming an intracluster correlation (ICC) of 0.02, based on estimates of rates of lymphedema provided by Alliance institutions as well as from CALGB 79804. The primary intent-to-treat analysis (ITT) included all eligible participants. Participants with missing lymphedema measurements at 12- and/or 18-months post-surgery and whose lymphedema status could not be determined were classified as not lymphedema-free. Lymphedema-free rates were adjusted for BMI at 18 months postsurgery, stratified by type of lymph node dissection and institution size (small, ? 275 new breast cancer patients annually; moderate, 276 to 450 new breast cancer patients annually; and large, ?450 new breast cancer patients annually), and compared between the 2 groups using an adjusted Cochran-Mantel-Haenszel test to account for ICC.25 Sensitivity analyses using complete case and simple and multiple imputations for missing data were conducted and confirmed original results. Imputation-based models produced similar findings. The difference in arm circumference from baseline to 12 and 18 months post-surgery at the site of the greatest difference was summarized and compared using the generalized estimating equation (GEE) model to account for cluster randomization. Self-reported ROM was assessed by participants choosing 1 of 6 illustrations best indicating how high they could reach above their head with each arm. Responses were dichotomized to reflect full ROM versus not full ROM. ROM differences were compared between study groups before surgery versus 12 and 18 months after surgery using GEE models to account for cluster randomization. Each arm was assessed independently, adjusting for baseline BMI, surgery type, type of lymph node dissection, affected arm being dominant, and receipt of radiation and/or chemotherapy. Analyses of these secondary endpoints were limited to complete cases. At 12 and 18 months, LEAP group participants were assessed for adherence to performing individualized arm exercises and wearing an elastic sleeve at least 75% of the time during heavy arm use, exercise, or travel. Statistical analyses concerning adherence were descriptive. Data collection and statistical analyses were conducted by the Alliance Statistics and Data Center. All analyses were completed on the study database frozen on April 30, 2016. Data quality was ensured by review of data by the Alliance Statistics and Data Center and by the study chairperson following Alliance policies. The trial was monitored at least twice annually by the Alliance Data and Safety Monitoring Committee. All analyses were conducted using SAS software version 9.4. Funding Information: Electra D. Paskett has received grants from Merck Foundation and Pfizer. Gini F. Fleming has been the principal investigator of an industry‐sponsored trial for Corcept, Abbvie/Tesaro, Roche/Genentech, Syndax, 47 Inc, Iovance, Syros, and Eisai. The other authors made no disclosures. Charles Loprinzi reported grants from NCI during the conduct of this study as indicated on his ICMJE form. Publisher Copyright: © 2020 American Cancer Society

PY - 2021/1/15

Y1 - 2021/1/15

N2 - Background: Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education-only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group-randomized trial across 38 cooperative group sites. Methods: The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self-reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a ≥10% difference in limb volume at any time post-surgery up to 18 months after surgery or diagnosis by a health provider. Cochran-Mantel-Haenszel tests were used to compare lymphedema-free rates between groups, stratified by lymph node surgery type. Self-reported ROM differences were compared between groups. Results: A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema-free rates were 58% (EO) versus 55% (LEAP) (P =.37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one-third wore a sleeve ≥75% of the time; 50% performed lymphedema exercises at least weekly. Conclusion: Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.

AB - Background: Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education-only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group-randomized trial across 38 cooperative group sites. Methods: The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self-reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a ≥10% difference in limb volume at any time post-surgery up to 18 months after surgery or diagnosis by a health provider. Cochran-Mantel-Haenszel tests were used to compare lymphedema-free rates between groups, stratified by lymph node surgery type. Self-reported ROM differences were compared between groups. Results: A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema-free rates were 58% (EO) versus 55% (LEAP) (P =.37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one-third wore a sleeve ≥75% of the time; 50% performed lymphedema exercises at least weekly. Conclusion: Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.

KW - breast cancer

KW - education

KW - exercise

KW - lymphedema

KW - prevention

KW - range of motion

UR - http://www.scopus.com/inward/record.url?scp=85092724790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85092724790&partnerID=8YFLogxK

U2 - 10.1002/cncr.33183

DO - 10.1002/cncr.33183

M3 - Article

C2 - 33079411

AN - SCOPUS:85092724790

SN - 0008-543X

VL - 127

SP - 291

EP - 299

JO - Cancer

JF - Cancer

IS - 2

ER -

A randomized study to prevent lymphedema in women treated for breast cancer: CALGB 70305 (Alliance)

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