Introduction
Materials and methods
Eligibility criteria
Information sources and search strategy
Reference screening
Data abstraction
Statistical analysis and synthesis
Results
Study type | Studies included in analysis | Total patients (n) | Mastectomy (%) | Breast conservation (%) | ALND (%) | SLNB (%) | Taxane chemotherapy (%) | RNI (%) |
---|---|---|---|---|---|---|---|---|
All Background Studies | 35 | 57,944 | 20,472 (35%) | 36,631 (63%) | 16,888 (29%) | 30,754 (53%) | 1,502 of 5,398 patients (27%)b | 2,607 of 10,184 patients (25%)b |
Background (no monitoring studies only) | 11 | 48,833 | 18,392 (37%) | 30,246 (61%) | 12,649 (25%) | 26,058 (53%) | 533 of 2,216 patients (24%)b | 503 of 2,680 patients (18%)b |
BIS Studies | 7 | 1,924 | 623 of 1,165 patients (53%)b | 541 of 1,165 patients (46%)† | 547 (28%) | 1125 (58%) | 314 of 948 patients (33%)b | 182 of 985 patients (18%)b |
Circumference Studies | 11 | 8,403 | 5,362 of 5,843 patients (91%)b | 736 (8%) | 6,213 (73%) | 2019 (24%) | 32 of 71 patients (46%)b | 139 of 180 patients (77%)b |
All Typesa | 50 | 67,712 | 26,436 (39%) | 37,858 (55%) | 23,134 (34%) | 33,845 (49%) | 1,817 of 6,383 patients (28%)b | 2,219 of 12,217 patients (18%)b |
Study | Location | Inclusion criteria | Exclusion criteria | Total patients (n) | Duration of follow-up (mean/median), years | LE definition | Patients progressed to BCRL (n) | Annual rate of progression (patients progressed/person-time) |
---|---|---|---|---|---|---|---|---|
Ammitzboll et al. [20] | Denmark | Women aged 18–75, operated with ALND for unilateral primary BC, able transport themselves, and able to participate in exercise intervention | Previous ALND either side, primary breast reconstruction, metastatic disease, and history of lymphoedema | 6 | 0·96 | > 3% interlimb volume difference (ILVD), increased score on the numeric rating scale (NRS) for cardinal symptoms of swelling, and if meeting two of four clinical assessment criteria | 1 | 0·17 |
Ammitzboll et al. [21] | Denmark | Women age 18–75 years, primary unilateral BC, ALND, and ability to participate in group exercise regimen | Distant metastases, previous ALND on contralateral side, and history of arm lymphedema | 158 | 1·00 | > 3% increase in ILVD | 32 | 0·20 |
Armer et al. [15] | USA | Women over 18, with cT0-T4, NI-2, M0 breast cancer, fine needle aspiration or core needle biopsy of axillary node documenting nodal metastasis at diagnosis | Prior ipsilateral axillary surgery, or prior SLNB; patients who had bilateral breast cancer, current limb infection, lymphangitis, or any other condition that would affect testing | 488 | 3·00 | A volume increase > 10% compared to baseline and /or the contralateral arm | 294 | 0·20 |
Bains et al. [23] | United Kingdom | Invasive breast cancer and undergoing axillary lymph node surgery | Not specified | 38 | 1·12 | 5–10% volume increase from Perometer and clinical signs of BCRL | 7 | 0·17 |
Barrio et al. [25] | USA | Female patients age > 18, newly diagnosed invasive or in situ breast carcinoma, and planned unilateral axillary surgery with either SLNB or ALND | Not specified | 186 | 1·52 | Relative arm volume difference (RAVD) of > 10% | 13 | 0·05 |
Basta et al. [26] | USA | Patients with breast cancer diagnosis and mastectomy | Patients not meeting mastectomy requirement, having lymphedema before mastectomy, and < 12 months of follow-up or mortality within 12 months of mastectomy | 3,136 | 4·20 | ICD-9 DX codes 457·0 and 457·1 | 325 | 0·02 |
Berlit et al. [28] | Germany | Used study sample from previously conducted study | Not specified | 42 | 1·00 | N/A – used circumference measurements and defined in previous study | 7 | 0·17 |
Black et al. [29] | USA | Pathologically node-negative disease and a documented axillary surgical procedure on women aged 66 years or older | Not specified | 31,274 | 5·00 | ICD-9 DX codes 457·0 and 457·1 for Lymphedema | 2502 | 0·08 |
Blaney et al. (2014) [16] | Ireland | Women, aged 18–99 years, newly diagnosed with stages I–III unilateral breast cancer from specialist diagnostic breast clinics in Belfast City Hospital and Ulster Hospital | History of breast cancer or lymphoedema, prior severe trauma/surgery upper limb, pacemaker/ metal implant, no baseline assessment, Stage IV disease, and other additional conditions (see Appendix) | 71 | 1·00 | BIA classification: L-Dex score of > 10 or a 10 U increase from baseline | 31 | 0·44 |
Bloomquist et al. [30] | Denmark | Breast cancer patients from exercise intervention, had received ≥ 1 cycle of chemotherapy, had a WHO performance status of 0 or 1 and approved to participate by treating oncologist | Patients that had recurrent cancer, deceased, or diagnosed BCRL prior to participation in "Body & Cancer" | 149 | 1·17 | An interlimb difference of > 2 cm at to two or more measures | 41 | 0·24 |
Boccardo et al. [31] | Italy | Candidates for Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) procedure during ALND | No afferent lymphatics could be found and because of massive metastatic disease | 74 | 4·00 | Missing–not specified. Volumetry used | 3 | 0·01 |
Bulley et al. [32] | United Kingdom | Women who had completed treatment (surgery, chemotherapy and radiotherapy), and who were attending review appointments | If they had recurrence, or were unable to complete non-translated questionnaires | 613 | 5·25 | Limb volume difference (LVD) was 10% or greater (unilateral treatment only) | 115 | 0·04 |
Cariati et al. [33] | England | All patients diagnosed with breast cancer who underwent ALND | Not specified | 273 | 2·67 | > 10% arm volume increase compared to contralateral arm by perometer or subjective assessment | 74 | 0·10 |
Cintolesi et al. [34] | United Kingdom | Women newly diagnosed with breast cancer | Not specified | 26 | 2·08 | Clinical Assessment Criteria or by the volume of each upper limb changes from baseline by Perometer | 10 | 0·18 |
Coromilas et al. [35] | USA | From SEER-Medicare database, women aged 65–90 with DCIS who underwent excisional breast procedure (BCS), simple mastectomy, total mastectomy with ALND, or skin-sparing mastectomy | Excluded patients with any code for invasive breast cancer | 10,504 | 1·00 | ICD-9 DX codes 457·0 and 457·1 | 714 | 0·07 |
Cowher et al. [36] | USA | Women undergoing mastectomy with CARE performed by the same surgeon | Not specified | 587 | 5·10 | Occupational therapist or surgeon’s note documenting a decreased function and/or quality of life due to arm swelling or pain | 20 | 0·01 |
De Groef et al. [38] | Belgium | Women treated for breast cancer, radiation therapy terminated ≥ 3 months ago, upper limb region pain score of ≥ 40 of 100 on VAS, presence of myofascial dysfunctions at upper limb region | Unable to attend therapeutic sessions and measurements for the entire duration, presence of shoulder pathologies for which surgical indications exist, or presence of current episodes of cancer or metastasis | 50 | 1·00 | > 5·0% increase of relative arm volume difference compared to baseline | 23 | 0·46 |
Feldman et al. [40] | USA | Female patients with breast cancer and documented axillary nodal metastasis undergoing planned ALND or modified radical mastectomy | Those not undergoing complete ALND, allergy to Lymphazurin blue dye, and pregnancy | 37 | 0·50 | > 2 cm discrepancy in circumferential size measurements between the affected and unaffected arms or a change from baseline | 7 | 0·38 |
Fu et al. [42] | USA | Women over 21 yoa, first time diagnosis of breast cancer (Stage I- III), and scheduled for surgical treatment | Women with metastatic cancer (Stage IV), prior history of breast cancer and lymphedema, and bilateral breast cancer | 140 | 1·00 | 10% LV increase from baseline in the ipsilateral arm compared to contralateral arm by perometer | 4 | 0·03 |
Fu et al. [43] | USA | Patients with non-metastatic invasive breast cancer who had undergone mastectomy and either SLNB or ALND as their first nodal surgery | Under 18, lumpectomy, no nodal surgery, pN stage: N0, neoadjuvant chemotherapy, cancer within 5 years | 151 | 3·63 | Not specified | 28 | 0·05 |
Fu et al. [41] | USA | Women over 21 yoa, first time diagnosis of breast cancer (stages 1–3), scheduled for surgical treatment | Diagnosed with metastatic cancer, prior history of breast cancer and lymphedema, bilateral breast cancer, artificial knee or hip, kidney failure, heart failure | 136 | 1·00 | L-Dex ratios greater than 7·1.[BIA measurements] | 18 | 0·13 |
Gennaro et al. [44] | Italy | Consecutive patients undergoing ARM with a diagnosis of axillary nodal involvement based on preoperative needle biopsy or a positive SLNB and scheduled for ALND | Not specified | 60 | 1·33 | Arm circumference measurements increasing by > 2 cm, and/or based on subjective symptoms and/or comparative lymphoscintigraphy | 9 | 0·11 |
Hopkins et al. [45] | USA | 321 of the CALGB 49,907 patients were also enrolled in a QOL companion trial | Not specified | 321 | 2·00 | Physician reported BCRL; Progression not specified | 24 | 0·04 |
Jammallo et al. [47] | USA | Patients undergoing treatment for primary breast underwent prospective lymphedema screening, had preoperative and postoperative measurements by Perometer | Previous bilateral breast surgery and measurements occurring after a patient was diagnosed with metastatic disease | 787 | 2·25 | RVC > 10% occurring > 3 months postoperative | 22 | 0·01 |
Jammallo et al. [46] | USA | Women undergoing treatment for newly diagnosed breast | Previous bilateral breast surgery and those with metastatic disease were excluded from the analysis | 324 | 1·25 | RVC greater than or equal to 10% | 20 | 0·05 |
Koehler et al. [49] | USA | Women having undergone early-stage surgical breast cancer treatment (lumpectomy or mastectomy) with a minimum removal of one axillary lymph node by SLNB | Previous surgical treatment for breast cancer or synchronous bilateral breast cancer, or a previous history of shoulder surgery, shoulder dysfunction, or history of upper extremity deep vein thrombosis | 36 | 1·50 | > 10% difference in volume, > 200 mL difference in volume, > 2 cm difference at any site on the upper extremity using circumferential measurements or an L-Dex > 10 | 6 | 0·11 |
Nguyen et al. [53] | USA | All incident breast cancer cases diagnosed in Olmsted County, MN residents in the Olmsted County Rochester Epidemiol-ogy Project Breast Cancer Cohort | Not specified | 1,794 | 10·00 | All cases with definite or probable lymphedema in the clinical notes | 209 | 0·01 |
O’Toole et al. [55] | USA | Women with primary breast cancer, underwent unilateral breast surgery, underwent preoperative and postoperative assessments, and at least one follow-up assessment > 3 months after surgery | Patients with bilateral breast or axillary surgery, distant metastasis or recurrence | 308 | 1·36 | An arm volume increase of > 5% RVC | 50 | 0·12 |
Sagen et al. [56] | Norway | ages 35–75 years, diagnosed with early-stage primary breast cancer, surgery with breast ablation or breast-conserving surgery with ALND or SLNB only | Too frail, inability to cognitively comprehend, metastasized breast cancer or other cancer, preoperative injuries, pathologic problems affecting upper limb function while performing tests | 391 | 2·50 | 10% arm volume increase compared to contralateral arm by Perometer | 40 | 0·04 |
Skuli et al. [57] | USA | Patient cohort who participated in a 60- to 90-min SV after referral by patients’ medical oncologists and occurred 1–3 months after completion of locoregional therapy and initial systemic therapy | Not specified | 87 | 2·42 | N/A–retrospective chart review | 20 | 0·10 |
Specht et al. [59] | USA | Women diagnosed with breast cancer | Patients who underwent bilateral breast or axillary surgery were excluded | 1,173 | 4·00 | RVC > 10% measured at least 3 months after surgery | 114 | 0·02 |
Swaroop et al. [60] | USA | Women diagnosed with unilateral breast cancer who underwent surgery and prospective screening for lymphedema | Arm measurements taken after bilateral breast surgery or a diagnosis of metastasis | 1,121 | 2·00 | RVC > 10% measured at least 3 months after surgery | 184 | 0·08 |
Warren et al. [65] | USA | Women who underwent surgery for unilateral or bilateral breast cancer | Patients with preexisting lymphedema | 1,476 | 2·12 | RVC > 10% measured at least 3 months after surgery | 202 | 0·06 |
Whelan et al. [62] | Canada | Women with invasive carcinoma of the breast and treated with breast-conserving surgery and SLNB or ALND and had positive axillary lymph nodes or negative axillary nodes with high-risk features | T4 tumors (clinical evidence of direct extension to chest wall or skin) or N2–3 nodes, distant metastasis, or serious nonmalignant disease that would preclude definitive radiation therapy | 1,832 | 9·50 | Not specified–clinical assessment | 117 | 0·01 |
Youssef et al. [64] | England | Patients diagnosed with micrometastasis in the axilla | Neoadjuvant chemotherapy treatment | 95 | 2·85 | Not specified–clinical assessment | 7 | 0·03 |
Darragh et al. [37] | Ireland | All patients undergoing a unilateral axillary procedure for breast cancer, preoperative measurements were required in addition to at least two postoperative readings | Previous bilateral procedures, previous axillary surgery, a pacemaker, a history of upper-limb DVT, arteriovenous fistulae, upper-limb fracture, and those who were pregnant | 354 | 4·17 | L-Dex values above the normal range or a change of more than 10 L-Dex units from baseline | 23 | 0·02 |
Erdogan et al. [39] | Turkey | Surgery due to early-stage breast cancer | History of bilateral breast cancer, previous axillary surgery, history of lymphedema, pacemakers or metal implants, secondary conditions that may affect the fluid disruption (See Appendix) | 37 | 1·00 | L-Dex ratios greater than 10 | 5 | 0·14 |
Kaufman et al. [8] | USA | Breast cancer patients undergoing definitive breast cancer surgery with no limitation on the axillary management technique | Implantable electronic devices, pregnancy, renal failure, and heart failure | 206 | 2·16 | L-Dex ratios greater than 10 from baseline | 0a | 0a |
Kilgore et al. [48] | USA | Breast cancer patients with unilateral disease undergoing treatments high-risk for BCRL | Not specified | 146 | 1·69 | BIS result of 2 standard deviations above baseline from preoperative assessment (> 10 points) | 9 | 0·04 |
Laidley et al. [50] | USA | Some form of axillary staging [SLNB or ALND], preoperative L-Dex assessment, and ≥ two subsequent L-Dex assessments | Bilateral axillary surgery, previously diagnosis of BCRL, pregnancy, and implanted electronic cardiac device | 326 | 1·81 | A change in > 10 L-Dex units | 11 | 0·02 |
Ridner et al. [17] | USA | Women ≥ 18 yoa with planned surgery for breast cancer, stage I–III invasive breast cancer or DCIS with at least one of these: mastectomy, axillary treatment, and taxane-based chemotherapy | Bilateral breast surgery, history of breast cancer; neoadjuvant chemotherapy; previous radiation to the breast, chest wall, or axilla; implanted medical device; previous lymphedema treatment; and other conditions (see Appendix) | 259 | 1·52 | An elevated L-Dex score of > 10 units from baseline | 2 | 0·01 |
Whitworth et al. [63] | USA | Patients with breast cancer undergoing surgery (either breast conservation or mastectomy), ALND or SLMB | Bilateral disease, electronic devices (i·e·, pacemakers), pregnancy, renal failure, and heart failure | 596 | 1·42 | L-Dex score greater than 10 points from baseline | 18 | 0·02 |
Armer et al. [15] | USA | Women over 18, with cT0-T4, NI-2, M0 breast cancer, fine needle aspiration or core needle biopsy of axillary node documenting nodal metastasis at diagnosis | Prior ipsilateral axillary surgery, or prior SLNB; patients who had bilateral breast cancer, current limb infection, lymphangitis, or any other condition that would affect testing | 488 | 3·00 | 2-cm increase from a tape measure, compared to baseline and/or the contralateral arm | 368 | 0·25 |
Ay et al. [22] | Turkey | Patients who underwent breast cancer surgery for stage II or III disease | Upper-limb trauma during the pre- and postoperative period, known vascular disease, serious thromboembolic event, neoadjuvant chemotherapy/ radiotherapy, and other conditions (See Appendix) | 5,064 | 5·33 | A difference of > 5% in circumference between the arms postoperatively | 1008 | 0·04 |
Ballal et al. [24] | Netherlands | Patients having surgical procedures for malignant breast disease | Inadequate recorded information, previously undergone ipsilateral breast cancer surgery to the axilla, or undergoing tissue flap reconstructions | 745 | 1·00 | An increase in the ipsilateral arm compared to the contralateral arm of more than 2 cm at any one point | 61 | 0·08 |
Benevento et al. [27] | Italy | Women over the age 25, absence of coagulopathy and/or liver disease, BMI = < 35, indication for ALND | Undergone previous breast surgeries and those who did not meet inclusion criteria | 60 | 1·00 | An increase in the ipsilateral arm compared to the contralateral arm of more than 2 cm at any one point | 5 | 0·08 |
Blaney et al. [16] | Ireland | Women, aged 18–99 years, newly diagnosed with stages I–III unilateral breast cancer from specialist diagnostic breast clinics in Belfast City Hospital and Ulster Hospital | History of breast cancer or lymphoedema, prior severe trauma/surgery upper limb, pacemaker/ metal implant, no baseline assessment, Stage IV disease, and other additional conditions (see Appendix) | 71 | 1·00 | Tape measurement: a ≥ 5% increase in proximal, distal or total percentage volume difference (PVD) from baseline | 28 | 0·39 |
Lorek et al. [51] | Poland | Patients with primary operative breast cancer who had received the SLNB procedure in combination with wide local excision (WLE) or simple mastectomy, or had SLNB prior to induction treatment | Not specified | 303 | 2·13 | A 10% difference between the limbs | 9 | 0·01 |
McLaughlin et al. [52] | USA | Patients from Mayo Clinic's registry | Did not complete 12 month follow-up | 120 | 1·00 | 10% increase in the ipsilateral arm when compared with the changes in the contralateral arm | 12 | 0·10 |
Ochalek et al. [54] | Poland | Women from previously conducted RCT following breast cancer surgery and axillary nodes removed | Symptoms and/or signs of infection in affected limb, signs of heart or renal failure, preoperative LE, previous bilateral lymph node dissection, and other conditions (see Appendix) | 45 | 1·00 | A volume increase > 10% compared with the volume before surgery | 7 | 0·16 |
Ridner et al. [17] | USA | Women ≥ 18 yoa with planned surgery for breast cancer, stage I–III invasive breast cancer or DCIS with at least one of these: mastectomy, axillary treatment, and taxane-based chemotherapy | Bilateral breast surgery, history of breast cancer; neoadjuvant chemotherapy; previous radiation to the breast, chest wall, or axilla; implanted medical device; previous lymphedema treatment; and other conditions (see Appendix) | 239 | 1·47 | volume change in the at-risk arm ≥ 10% above the presurgical baseline | 10 | 0·03 |
Soran et al. [58] | USA | Patients who underwent ALND for BC in LE monitoring program | Patients with preoperatively diagnosed clinical or subclinical LE and prior trauma on the operated upper limb | 180 | 1·76 | Girth difference of ≥ 2·0 cm in the involved limb versus the uninvolved limb | 22 | 0·07 |
Wetzig et al. [61] | Australia | Women with unifocal breast cancers < 3 cm diameter and clinically negative lymph nodes | Not specified | 1,088 | 5·00 | An increase of 15% or more from baseline in upper limb volume | 28 | 0·01 |
No intervention (background rate) | Monitoring with BIS | Monitoring with circumference | Comparative rate ratio | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Included studies (n) | Incidence (%; 95% CI) | Included studies (n) | Incidence (%; 95% CI) | Rate ratioa | p-value | Included studies (n) | Incidence (%; 95% CI) | Rate ratiob | p-value | BIS vs. circumference | p-value | |
Overall pooled estimate | 35 | 4·9 (4·3–5·5) | 7 | 1·5 (0·6–2·4) | 0·31 | < 0·001 | 11 | 7·7 (5·6–9·8) | 1·57 | < 0·001 | 0·19 | < 0·001 |
By follow-up duration | ||||||||||||
≤ 2 years | 18 | 10·1 (8·0–12·2) | 5 | 1·9 (0·7–3·2) | 0·19 | < 0·001 | 7 | 9·4 (5·5–13·3) | 0·93 | 0·36 | 0·20 | < 0·001 |
> 2 years | 17 | 3·4 (2·8–3·9) | 2 | 0·8 (− 0·6–2·2) | 0·24 | < 0·001 | 4 | 6·9 (4·1–9·8) | 2·03 | < 0·001 | 0·12 | < 0·001 |
By study type | ||||||||||||
Prospective | 19 | 7·9 (6·1–9·8) | 4 | 2·1 (0·0–4·1) | 0·27 | < 0·001 | 6 | 11·0 (5·8–16·3) | 1·39 | < 0·001 | 0·19 | < 0·001 |
Randomized clinical trials | 6 | 10·1 (6·1–14·0) | 1 | 0·5 (− 0·2–1·2) | 0·05 | < 0·001 | 3 | 7·1 (0·4–13·8) | 0·70 | 0·04 | 0·07 | < 0·001 |
Retrospective | 10 | 3·5 (2·7–4·4) | 2 | 1·6 (1·1–2·2) | 0·46 | < 0·001 | 2 | 5·8 (1·5–10·2) | 1·66 | < 0·001 | 0·28 | < 0·001 |
No intervention (background rate) | Monitoring with BIS | Monitoring with circumference | Comparative rate ratio | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Included studies (n) | Annualized Incidence (%; 95% CI) | Included studies (n) | Annualized Incidence (%; 95% CI) | Rate Ratioa | p-value | Included studies (n) | Annualized incidence (%; 95% CI) | Rate ratiob | p-value | BIS vs. circumference | p-value | |
Axillary lymph node dissection (ALND) | ||||||||||||
≤ 50% | 17 | 4·4 (3·6–5·2) | 4 | 1·4 (0·2–2·5) | 0·32 | < 0·001 | 3 | 8·6 (6·7–10·5) | 1·95 | < 0·001 | 0·16 | < 0·001 |
> 50% | 16 | 6·8 (5·3–8·4) | 2 | 6·8 (− 2·2–15·8) | 1·00 | 1·0 | 5 | 15·4 (5·0–25·8) | 2·26 | < 0·001 | 0·44 | < 0·001 |
Sentinel lymph node biopsy (SLNB) | ||||||||||||
≤ 50% | 10 | 6·0 (4·5–7·5) | 1 | 13·5 (1·7–25·4) | 2·25 | 0·06 | 2 | 14·4 (− 6·6–35·4) | 2·40 | < 0·001 | 0·94 | 0·88 |
> 50% | 15 | 5·0 (3·8–6·2) | 4 | 1·4 (0·2–2·5) | 0·28 | < 0·001 | 6 | 6·1 (3·1–9·1) | 1·22 | < 0·001 | 0·23 | < 0·001 |
Mastectomy | ||||||||||||
≤ 40% | 17 | 4·1 (3·4–4·8) | 1 | 13·5 (1·7–25·4) | 3·29 | 0·004 | 4 | 14·5 (2·1–26·8) | 3·54 | < 0·001 | 0·93¥ | 0·87 |
> 40% | 15 | 5·2 (3·9–6·6) | 3 | 1·3 (− 0·2–2·8) | 0·25 | < 0·001 | 3 | 6·1 (2·7–9·5) | 1·17 | < 0·001 | 0·21 | < 0·001 |