lymphedema ( le ) is a common and debilitating condition in breast cancer survivors characterized by regional swelling , typically in one or both arms . it is characterized by an accumulation of protein - rich fluids caused by an interruption in the axillary lymphatic drainage from the arm . due to the increased survival of breast cancer patients , le has emerged as an important long - term morbidity , resulting in functional , cosmetic , and psychological problems , all of which may significantly impact quality of life . despite the frequency of this condition , there are no uniform criteria for defining le . symptom duration is generally not stated as part of the definition of le , with a diagnosis of le made primarily on the presence of swelling alone . after the initial onset of symptoms , many patients experience a spontaneous resolution of swelling without progressing to a persistent condition . this transient swelling is typically of less than six - month duration . at the time of initial swelling , determining whether a patient has either transient lymphedema ( tle ) or persistent lymphedema ( ple ) is important , particularly among ple patients who must learn to cope with this life - long complication through the use of proactive education and management . in contrast , tle patients , whose symptoms can be expected to resolve naturally , may benefit by avoiding unnecessary treatment . however , the incidence , time course of tle , and risk factors associated with progression to ple from initial swelling remain poorly understood . in this study , we analyzed the incidence and risk factors for development of tle and ple after initial swelling and estimated the ratio of tle and ple based on the presence of known treatment - related factors . the study population consisted of 1,255 consecutive breast cancer patients who underwent curative breast surgery with axillary lymph node dissection ( alnd ) at the national cancer center , korea between may 2004 and april 2009 . those with synchronous or metachronous contralateral breast cancer ( n=7 ) and those with a follow - up period of < 3 years were excluded ( n=175 ) . the remaining 1,073 patients were included in the current analysis , which was performed in accordance with the guidelines of the institutional review board at the national cancer center of korea . surgery consisted of either modified radical mastectomy ( mrm ) or breast - conserving surgery ( bcs ) , as necessary , based on the surgeon s recommendations and tumor characteristics . the general criteria for patient selection for bcs included a lack of initial extensive skin or chest wall involvement , absence of extensive microcalcifications or multifocal disease , the anticipated adequacy of residual breast tissue following bcs , and an absolute contraindication against breast irradiation . adjuvant chemotherapy ( act ) consisted of six to eight courses of a non - taxane containing ( n=264 ) or taxane - containing ( n=414 ) regimen . neoadjuvant chemotherapy ( nct ) consisted of four to six courses of anthracycline - based , taxane - based , or combined anthracycline - taxane therapy . adjuvant hormonal suppression therapy using tamoxifen or an aromatase inhibitor was offered to 951 patients ( 79% ) with estrogen receptor  positive or progesterone receptor  positive tumors . radiation therapy ( rt ) was delivered to all bcs and mrm patients with pt3 , pn2-pn3 , or pn1 with extracapsular invasion of the involved nodes for patients treated with act . all patients who received nct were treated with rt , irrespective of the type of surgery . planning computed tomography scans were obtained in all patients , and rt was performed using conventional techniques . typically , 50.4 gy were delivered in 28 fractions to the ipsilateral breast or chest wall . after bcs , all patients received an electron boost ( median , 10 gy ) to the lumpectomy cavity . ipsilateral axillary apex and supraclavicular rt ( scrt ) was delivered to patients of pn2 to pn3 status who received act , and to all patients who received nct ( median , 45 gy ) . internal mammary nodal rt was administered to only 17 patients ( 5% ) with clinically positive internal mammary nodes . determination of le was based on both objective ( circumference measurement ) and subjective ( patient perception of arm edema ) assessments , as described previously . beginning in 2004 , measurement and assessment of le was performed in all patients by a single physician ( k.h.s . ) as part of a prospective database . at each follow - up visit , patients were asked whether they were currently experiencing swelling , heaviness , thickness , tiredness , or pain in their affected arms , regardless of reported differences in arm size . patients were also asked to recall preoperative arm condition , with no patient reporting preoperative arm swelling . circumference measurements of the ipsilateral and contralateral arms at 10 cm above the antecubital fold were performed regularly every 6 months , beginning at least 6 months postoperatively until the last follow - up . ipsilateral arm swelling of more than 5% of the circumferential difference without special conditions ( such as a previous accident or injury to the contralateral arm ) was considered objective le . graded scales combining subjective symptoms and the common terminology criteria for adverse events ver . a difference of 5%-10% in arm measurement or only self - perception of arm swelling with less than 5% measurement difference was scored as grade 1 ; arm measurement differences of 10%-30% or > 30% were scored as grades 2 or 3 , respectively . assessments were made beginning at least 6 months postoperatively and regularly every 6 months until the last follow - up . le events were defined as any case of arm swelling , including both objectively and subjectively defined incidents . tle was defined as a single episode of arm swelling that resolved spontaneously at the next follow - up . ple was defined as arm swelling that persisted over two consecutive follow - up examinations . the rates of le were calculated using the kaplan - meier method , and the development of le was measured from the date of surgery . univariate cox proportional hazards models were used for evaluation of risk factors associated with the development of le . the factors included age ( < 50 years vs.  50 years ) , body mass index ( bmi ; < 25 kg / m vs.  25 kg / m ) , t classification ( t1-t2 vs. t3-t4 ) , n classification ( n0-n1 vs. n2-n3 ) , stage ( i - ii vs. iii ) , type of surgery ( bcs vs. mrm ) , number of dissected axillary lymph nodes ( n - aln ;  10 vs. > 10 ) , and regimen of chemotherapy ( not performed or chemotherapy without taxane vs. chemotherapy with taxane ) . variables shown to be significant ( p < 0.05 ) in univariate analysis were selected for multivariate analysis . all statistical tests were two - sided , and statistical significance was defined as a p - value < 0.05 . the study population consisted of 1,255 consecutive breast cancer patients who underwent curative breast surgery with axillary lymph node dissection ( alnd ) at the national cancer center , korea between may 2004 and april 2009 . those with synchronous or metachronous contralateral breast cancer ( n=7 ) and those with a follow - up period of < 3 years were excluded ( n=175 ) . the remaining 1,073 patients were included in the current analysis , which was performed in accordance with the guidelines of the institutional review board at the national cancer center of korea . surgery consisted of either modified radical mastectomy ( mrm ) or breast - conserving surgery ( bcs ) , as necessary , based on the surgeon s recommendations and tumor characteristics . the general criteria for patient selection for bcs included a lack of initial extensive skin or chest wall involvement , absence of extensive microcalcifications or multifocal disease , the anticipated adequacy of residual breast tissue following bcs , and an absolute contraindication against breast irradiation . adjuvant chemotherapy ( act ) consisted of six to eight courses of a non - taxane containing ( n=264 ) or taxane - containing ( n=414 ) regimen . neoadjuvant chemotherapy ( nct ) consisted of four to six courses of anthracycline - based , taxane - based , or combined anthracycline - taxane therapy . adjuvant hormonal suppression therapy using tamoxifen or an aromatase inhibitor was offered to 951 patients ( 79% ) with estrogen receptor  positive or progesterone receptor  positive tumors . radiation therapy ( rt ) was delivered to all bcs and mrm patients with pt3 , pn2-pn3 , or pn1 with extracapsular invasion of the involved nodes for patients treated with act . all patients who received nct were treated with rt , irrespective of the type of surgery . planning computed tomography scans were obtained in all patients , and rt was performed using conventional techniques . typically , 50.4 gy were delivered in 28 fractions to the ipsilateral breast or chest wall . after bcs , all patients received an electron boost ( median , 10 gy ) to the lumpectomy cavity . ipsilateral axillary apex and supraclavicular rt ( scrt ) was delivered to patients of pn2 to pn3 status who received act , and to all patients who received nct ( median , 45 gy ) . internal mammary nodal rt was administered to only 17 patients ( 5% ) with clinically positive internal mammary nodes . determination of le was based on both objective ( circumference measurement ) and subjective ( patient perception of arm edema ) assessments , as described previously . beginning in 2004 , measurement and assessment of le was performed in all patients by a single physician ( k.h.s . ) as part of a prospective database . at each follow - up visit , patients were asked whether they were currently experiencing swelling , heaviness , thickness , tiredness , or pain in their affected arms , regardless of reported differences in arm size . patients were also asked to recall preoperative arm condition , with no patient reporting preoperative arm swelling . circumference measurements of the ipsilateral and contralateral arms at 10 cm above the antecubital fold were performed regularly every 6 months , beginning at least 6 months postoperatively until the last follow - up . ipsilateral arm swelling of more than 5% of the circumferential difference without special conditions ( such as a previous accident or injury to the contralateral arm ) was considered objective le . graded scales combining subjective symptoms and the common terminology criteria for adverse events ver . 4.0 were used for le scoring . a difference of 5%-10% in arm measurement or only self - perception of arm swelling with less than 5% measurement difference was scored as grade 1 ; arm measurement differences of 10%-30% or > 30% were scored as grades 2 or 3 , respectively . assessments were made beginning at least 6 months postoperatively and regularly every 6 months until the last follow - up . le events were defined as any case of arm swelling , including both objectively and subjectively defined incidents . tle was defined as a single episode of arm swelling that resolved spontaneously at the next follow - up . ple was defined as arm swelling that persisted over two consecutive follow - up examinations . the rates of le were calculated using the kaplan - meier method , and the development of le was measured from the date of surgery . univariate cox proportional hazards models were used for evaluation of risk factors associated with the development of le . the factors included age ( < 50 years vs.  50 years ) , body mass index ( bmi ; < 25 kg / m vs.  25 kg / m ) , t classification ( t1-t2 vs. t3-t4 ) , n classification ( n0-n1 vs. n2-n3 ) , stage ( i - ii vs. iii ) , type of surgery ( bcs vs. mrm ) , number of dissected axillary lymph nodes ( n - aln ;  10 vs. > 10 ) , and regimen of chemotherapy ( not performed or chemotherapy without taxane vs. chemotherapy with taxane ) . variables shown to be significant ( p < 0.05 ) in univariate analysis were selected for multivariate analysis . all statistical tests were two - sided , and statistical significance was defined as a p - value < 0.05 . the median age at diagnosis was 47 years ( range , 26 to 81 years ) . in terms of disease stage , 213 patients ( 19.8% ) were diagnosed with stage i , 505 patients ( 47.1% ) with stage ii , and 355 patients ( 33.1% ) with stage iii . bcs was performed in 814 patients ( 75.9% ) and mrm in 259 patients ( 24.1% ) . act was administered to 678 patients ( 63.2% ) and nct to 299 patients ( 27.9% ) . taxane - based regimen was administered to 706 patients ( 65.8% ) and non - taxane - based regimen to 271 patients ( 25.3% ) . rt was administered to 965 patients ( 89.9% ) ; 410 patients ( 38.2% ) received breast or chest wall irradiation alone , and 555 patients ( 51.7% ) received breast irradiation with scrt . the median follow - up duration from the date of surgery was 5.1 years ( range , 3.0 to 8.7 years ) . le events were reported in 370 patients ( 34.5% ) , consisting of 120 patients ( 11.2% ) with tle and 250 ( 23.3% ) with ple . the final le grade of 250 ple patients was grade 1 in 188 , grade 2 in 60 , and grade 3 in 2 . initial le grade of all 370 patients was grade 1 in 351 ( 32.7% ) and grade 2 in 19 ( 1.8% ) . a total of 120 of 351 patients who were initial grade 1 le were limited to tle ( 34% ) and the remaining 231 patients progressed to ple ( 66% ) . the initial swelling for tle patients was all grade 1 edema . among the 119 grade 1 patients who had both subjective symptoms and objective differences at initial swelling , 95 ( 80% ) progressed to ple . all 19 patients with grade 2 le at the time of initial diagnosis progressed to ple . among ple patients , 49 of 231 patients initially diagnosed as grade 1 eventually progressed to grade 2 , with one patient progressing to grade 3 . the overall 5-year cumulative incidence of tle and ple was 12.5% and 25.3% , respectively ( fig . le events occurred within 1 year after surgery in 73% of cases , 2 years in 91% of cases , and 3 years in 98% of cases . in ple patients , le events occurred within 1 year after surgery in 58% of cases , 2 years in 83% of cases , and 3 years in 93% of cases . results of univariate analysis of patient- , disease- , and treatment - related factors associated with development of tle and ple are shown in table 2 . in univariate analysis , higher rates of tle development showed significant correlation with advanced stage at diagnosis ( iii ) , n - aln ( > 10 ) , chemotherapy regimen ( with taxane ) , and rt ( breast with scrt ) ; higher rates of ple development showed correlation with advanced stage at diagnosis ( iii ) , type of surgery ( mrm ) , n - aln ( > 10 ) , chemotherapy regimen ( with taxane ) , and rt ( breast with scrt ) . patients with more advanced stages of disease showed higher rates of le ( 12.4% in stage iii vs. 10.6% in stage i or ii for tle , 41.7% vs. 14.2% for ple ; p < 0.001 ) . the rates of ple in patients who underwent bcs and mrm were 21.6% and 28.2% , respectively ( p=0.02 ) . the le rates for n - alns  10 and > 10 for tle were 9% and 13% , respectively ( p=0.001 ) , compared with 13.7% and 31.3% , respectively , for ple ( p < 0.001 ) . regarding chemotherapy regimens , chemotherapy with taxane showed significant association with an increased risk of both tle and ple , compared with patients receiving no chemotherapy or chemotherapy without taxane ( 13.5% vs. 6.8% for tle , 33.0% vs. 4.6% for ple ; p < 0.001 ) . incidences of tle and ple were significantly higher in patients who received breast rt with scrt than in patients who received no rt or breast rt only ( 14.2% vs. 7.9% for tle , 37.8% vs. 7.7% for ple ; p < 0.001 ) . factors not significantly associated with le outcomes included age and bmi in both tle and ple , with tle also showing no association with type of surgery . in multivariate analysis using a stepwise backward selection procedure , chemotherapy with taxane ( hazard ratio [ hr ] , 1.86 ; p=0.03 ) and breast rt with scrt ( hr , 2.03 ; p=0.003 ) were independent risk factors for tle development ( table 3 ) . the advanced stage and n - aln did not affect tle . for ple development , advanced stage ( hr , 1.49 ; p=0.006 ) , chemotherapy with taxane ( hr , 3.74 ; p < 0.001 ) , and breast rt with scrt ( hr , 2.74 ; p < the treatment - related factors n - aln , scrt , and taxane chemotherapy have been shown to significantly affect the development of le ; therefore we examined whether the tendency of tle and ple could be estimated using those factors . the incidences of tle and ple relative to the number of treatment factors in 351 patients with initial grade 1 swelling are shown in table 4 . among 15 patients who had no risk factors , 13 patients ( 87% ) sixteen of 36 patients ( 44% ) with one risk factor were tle ; the remaining 20 ( 56% ) were ple . the incidences of tle and ple in 107 patients with two risk factors increased to 36% ( n=39 ) and 64% ( n=68 ) , respectively , to an approximate ratio of 1:2 . of the 193 patients with three risk factors , the approximate ratio of tle to ple was 1:3 . the median follow - up duration from the date of surgery was 5.1 years ( range , 3.0 to 8.7 years ) . le events were reported in 370 patients ( 34.5% ) , consisting of 120 patients ( 11.2% ) with tle and 250 ( 23.3% ) with ple . the final le grade of 250 ple patients was grade 1 in 188 , grade 2 in 60 , and grade 3 in 2 . initial le grade of all 370 patients was grade 1 in 351 ( 32.7% ) and grade 2 in 19 ( 1.8% ) . a total of 120 of 351 patients who were initial grade 1 le were limited to tle ( 34% ) and the remaining 231 patients progressed to ple ( 66% ) . the 119 grade 1 patients who had both subjective symptoms and objective differences at initial swelling , 95 ( 80% ) progressed to ple . all 19 patients with grade 2 le at the time of initial diagnosis progressed to ple . among ple patients , 49 of 231 patients initially diagnosed as grade 1 eventually progressed to grade 2 , with one patient progressing to grade 3 . the overall 5-year cumulative incidence of tle and ple was 12.5% and 25.3% , respectively ( fig . le events occurred within 1 year after surgery in 73% of cases , 2 years in 91% of cases , and 3 years in 98% of cases . in ple patients , le events occurred within 1 year after surgery in 58% of cases , 2 years in 83% of cases , and 3 years in 93% of cases . results of univariate analysis of patient- , disease- , and treatment - related factors associated with development of tle and ple are shown in table 2 . in univariate analysis , higher rates of tle development showed significant correlation with advanced stage at diagnosis ( iii ) , n - aln ( > 10 ) , chemotherapy regimen ( with taxane ) , and rt ( breast with scrt ) ; higher rates of ple development showed correlation with advanced stage at diagnosis ( iii ) , type of surgery ( mrm ) , n - aln ( > 10 ) , chemotherapy regimen ( with taxane ) , and rt ( breast with scrt ) . patients with more advanced stages of disease showed higher rates of le ( 12.4% in stage iii vs. 10.6% in stage i or ii for tle , 41.7% vs. 14.2% for ple ; p < 0.001 ) . the rates of ple in patients who underwent bcs and mrm were 21.6% and 28.2% , respectively ( p=0.02 ) . the le rates for n - alns  10 and > 10 for tle were 9% and 13% , respectively ( p=0.001 ) , compared with 13.7% and 31.3% , respectively , for ple ( p < 0.001 ) . regarding chemotherapy regimens , chemotherapy with taxane showed significant association with an increased risk of both tle and ple , compared with patients receiving no chemotherapy or chemotherapy without taxane ( 13.5% vs. 6.8% for tle , 33.0% vs. 4.6% for ple ; p < 0.001 ) . incidences of tle and ple were significantly higher in patients who received breast rt with scrt than in patients who received no rt or breast rt only ( 14.2% vs. 7.9% for tle , 37.8% vs. 7.7% for ple ; p < 0.001 ) . factors not significantly associated with le outcomes included age and bmi in both tle and ple , with tle also showing no association with type of surgery . in multivariate analysis using a stepwise backward selection procedure , chemotherapy with taxane ( hazard ratio [ hr ] , 1.86 ; p=0.03 ) and breast rt with scrt ( hr , 2.03 ; p=0.003 ) were independent risk factors for tle development ( table 3 ) . the advanced stage and n - aln did not affect tle . for ple development , advanced stage ( hr , 1.49 ; p=0.006 ) , chemotherapy with taxane ( hr , 3.74 ; p < 0.001 ) , and breast rt with scrt ( hr , 2.74 ; p < 0.001 ) were independent risk factors . the treatment - related factors n - aln , scrt , and taxane chemotherapy have been shown to significantly affect the development of le ; therefore we examined whether the tendency of tle and ple could be estimated using those factors . the incidences of tle and ple relative to the number of treatment factors in 351 patients with initial grade 1 swelling are shown in table 4 . among 15 patients who had no risk factors , 13 patients ( 87% ) sixteen of 36 patients ( 44% ) with one risk factor were tle ; the remaining 20 ( 56% ) were ple . the incidences of tle and ple in 107 patients with two risk factors increased to 36% ( n=39 ) and 64% ( n=68 ) , respectively , to an approximate ratio of 1:2 . of the 193 patients with three risk factors , the approximate ratio of tle to ple was 1:3 . le is an adverse and chronic condition affecting a considerable number of breast cancer survivors . the incidence of le among patients with breast cancer varies from less than 5% with lumpectomy alone to more than 60% when treatment includes mastectomy with alnd and rt . reports of the incidence of each condition are also inconsistent due to the variation in the criteria used to define le and the variety of assessment techniques . here , we used a grading scale combining both the objective method of circumference measurement and the subjective method of patient perception of arm edema to complement the accuracy of each method . le was then further subdivided in tle and ple according to presence or absence of arm swelling during the 6-month follow - up examination . ple ( chronic ) is of greater than 6 months in duration , whereas tle typically lasts less than 6 months and is related to pitting edema without brawny skin changes ; this distinction allowed for a clear demarcation between the two types of le . examination of tle is important , as the natural history of the condition , including incidence , time course , and risk factors , are not well documented in the literature . werner et al .   reported that transient and persistent edema occurred in 7% and 12% of women , respectively , in a study of 282 patients with stage i or ii breast cancer who received bcs with alnd . in which 23.1% of patients experienced mild le that generally resolved , or diminished to the point of only mild flare - ups . in terms of timing , the majority of swelling in the first year was shown to be largely transient , with factors including exercise and taxane chemotherapy associated with swelling incidence . in our current study , the overall 5-year cumulative incidence of tle was 12.5% , while that of ple was 25.3% . the onset of first swelling in patients with tle was generally earlier compared to those with ple , possibly due to acute swelling associated with three breast cancer treatment modalities . of the tle patients , 73% developed swelling within 1 year after surgery , compared to only 58% of ple patients . we have since expanded on this finding , showing a clear association between chemotherapy and an increased risk of le in the context of both act and nct , with taxane identified as an independent risk factor for le . in the current study , chemotherapy with taxane , compared with no chemotherapy or chemotherapy without taxane , increased the risk of tle and ple . this observation was unsurprising , as taxane is known to cause generalized edema by increasing the amount of extracellular fluid in the interstitial compartment . the increased incidence of le in the ipsilateral arm following taxane - based chemotherapy has been shown to persist for at least 6 months after cessation chemotherapy ; however , generalized swelling in the legs and contralateral arm resolved within 6 months after chemotherapy . reported that taxane - based chemotherapy causes preferential transient swelling in the first year following surgery . the risk of le has been shown to increase in response to an increase in n - alns . here , n - aln > 10 was identified as a risk factor for both ple and tle by univariate analysis . scrt was also a strong contributing factor , associated with a 2- to 4.5-fold increase in the risk of le . similarly , coen et al .   reported a significant increase in the risk of le from 1.8% to 8.9% over a 10-year follow - up period in patients with bcs following the addition of scrt . in this study , scrt was identified as an independent risk factor for development of not only ple but also tle in a multivariate analysis . because le is progressive , and early diagnosis could lead to more effective treatment , diagnosis of le at the earliest possible stage is important . at first presentation of arm swelling , understanding of risk factors associated with ple and predicting whether this condition is expected to be self - limiting or persistent may enable clinicians to mitigate ple incidence and severity by providing proactive education and management . this study showed that the tendency of tle and ple after initial grade 1 swelling could be estimated using a combination of three treatment - related risk factors : n - aln , scrt , and taxane chemotherapy . in patients with no risk factor , ~90% of swelling events were limited in scope , and had completely disappeared within 6 months . however , in all other patients , the likelihood of edema persisting or progressing to a more serious form increased according to the number of risk factors . the approximate ratio of tle vs. ple was 1:1 in patients with one risk factor , 1:2 in patients with two factors , and 1:3 in those with three risk factors . as mentioned above , 95 of 119 grade 1 patients ( 80% ) who had both subjective symptoms and an objective arm circumference difference progressed to ple , implying that patients who had at least one risk factor or both subjective and objective symptoms of le may require more careful follow - up . patient - related factors  such as obesity , hand use , injury , and infection  could be modified to reduce the risk for these patients . in a study of 109 patients with mild le at le diagnosis by bar ad et al . , 52 ( 48% ) progressed to more severe stages at some point during the first 5 years of follow - up . in our study , 49 of 351 patients ( 14% ) initially diagnosed as grade 1 eventually progressed to grade 2 , with one patient progressing to grade 3 . limitations of our study include the lack of preoperative baseline information on arm circumference or the ability to interview patients about arm swelling . in a meta - analysis by disipio et al . , even in the absence of pretreatment le status , prevalence was thought to be a reasonable estimate of incidence because the proportion of female patients with le before surgery for breast cancer has been reported to be very low . the subjective patient s perception of arm edema was dependent on patient recall or swelling sense at the time of the outpatient clinic visit . for objective measurements , only the upper arm circumference was measured ; hence , localized forearm or hand edema would not have been detected , although subjective assessments may have been sufficient to overcome this limitation . in addition , we used a percentage difference rather than an actual difference in arm circumference for consideration of different bmi among patients and body weight changes overtime in each patient . the other limitation is that our study did not include data regarding treatment of le . however , in our hospital , education on the modification of patient - related factors such as reducing excessive arm use , avoiding arm infection of injury , and weight control was mandatorily provided to all breast cancer patients regardless of swelling episodes . in addition , most patients with objective le at the first swelling episodes were managed using a compression stocking or bandage . in conclusion , one - third of initial swelling events were transient in nature , with the remaining two - thirds progressing to a more persistent form of le . among patients with tle , chemotherapy with taxane and rt covering the breast and supraclavicular region were identified as independent risk factors . the approximate incidence ratios of tle and ple in patients with initial grade 1 edema were estimated according to treatment - related factors , which could facilitate prediction and treatment of this life - long , undesired complication .