Skip to main content

Risk factors for the development of severe breast cancer-related lymphedema: a retrospective cohort study



Severe lymphedema presents a challenge in terms of treatment due to the significant formation of scar tissue that accompanies it. The aim of this study was to identify intraoperative and preoperative risk factors of severe lymphedema and to develop a nomogram for estimating the risk of severe lymphedema within 3 years of surgery.


Data was collected from a retrospective cohort of 326 patients with BCRL at the Zhejiang Cancer Hospital from November 2015 to November 2018. Univariate and multivariate logistic regression analysis was conducted to identify predictive indicators of severe lymphedema. A nomogram was developed to further improve the clinical applicability.


In the retrospective cohort, the ratio of severe/non-severe lymphedema within 3 years of surgery was 1:3. Independent risk factors for severe lymphedema were determined to be age, positive lymph nodes, interpectoral (Rotter’s) lymph nodes (IPNs) dissection, and educational level. IPNs dissection was found to contribute greatly to the development of severe lymphedema with a higher odds ratio (7.76; 95% CI: 3.87–15.54) than other risk factors. A nomogram was developed by integrating age, positive lymph nodes, IPNs dissection, and educational level, which yielded a C-index of 0.810 and 0.681 in the training and validation cohort, respectively. This suggested a moderate performance of the nomogram in predicting the risk of severe lymphedema within 3 years of surgery. The cut-off values of the low-, medium- and high-risk probabilities were 0.0876 and 0.3498, and the severe lymphedema exhibited a significantly higher risk probability as compared with the non-severe lymphedema.


This study identified the risk factors of severe lymphedema and highlighted the substantial contribution of IPNs dissection to the severity of lymphedema.

Peer Review reports


Lymphedema is a condition caused by impairment of the lymphatic system, which usually results in progressive swelling due to an abnormal accumulation of lymph fluid [1, 2]. Sufferers can experience negative physical, psychological, and emotional effects, and incur additional financial burdens [3]. Breast cancer-related lymphedema (BCRL) can be a painful, potential debilitating complication after axillary dissection and regional nodal irradiation for breast cancer, having a rate ranging from 9 to 65% [4,5,6]. But due to the wider use of sentinel lymph node biopsy, the incidence of BCRL has decreased significantly, estimated to be 1–7% [7].

Although secondary lymphedema symptoms are usually mild and temporary, this group is three times more likely to suffer from moderate or severe edema compared to those with no symptoms[8]. The treatment of mild to moderate secondary lymphedema symptoms involves manual lymphatic drainage, massage, compression garments, and physical therapy [9]. However, for patients with advanced lymphedema, few treatments, including surgery, can halt the progress of the condition. Despite being the standard treatment for breast cancer, axillary lymph node dissection (ALND) may result in lymphedema in 20–50% of patients [10]. Other factors influencing include modified radical mastectomy (MRM), radiotherapy, body mass index (BMI), cellulitis, hypertension, education level, and chemotherapy[5, 11,12,13,14,15,16,17,18].

To date, no systematic evaluation of severe lymphedema risk factors has been conducted. In this study, we conducted a retrospective clinical analysis of BCRL patients who underwent either conservative breast cancer surgery or mastectomy, with the ami of pinpointing the risk factors that are likely to lead to severe lymphedema. A nomogram was further developed to facilitate the prediction of severe lymphedema risk in future patients.

Methods and materials

Study design and patients

This retrospective analysis was conducted in compliance with the tenets of the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Zhejiang Cancer Hospital. The Ethics committee of Zhejiang Cancer Hospital waived the need for written informed consent due to the retrospective nature of the study. The electronic report database of Zhejiang Cancer Hospital was searched for patients with BCRL who underwent conservative breast cancer surgery or mastectomy from November 2015 to November 2018. Patients with a 3-year period from operation time were enrolled in the study, while for those with multiple diagnostic records, the most severe degree of edema was adopted as their final outcome. The whole cohort were randomly divided into the training cohort (228) and validation cohort (98) with a ratio of 7:3.

Inclusion and exclusion criteria

Inclusion criteria consist of female participants aged 18 to 75 years old who have been diagnosed with lymphoedema within 3 years of having undergone breast cancer surgery. Exclusion criteria include patients with recurrent or metastatic breast cancer; a history of upper limb surgery or trauma; systemic diseases known to cause swelling (e.g. myocardial infarction, renal dysfunction, gastrointestinal diseases); pregnancy or lactation; and prior treatment for arm lymphoedema.

Predictor selection

Only those potential predictors with prior clinical knowledge were selected for consideration[19,20,21,22,23]. These were identified from the published literature and clinical reasoning and included age, tumor size, circle of chemotherapy, serum cholesterol, BMI, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, neoadjuvant chemotherapy, docetaxel, chemotherapy, radiotherapy, education level, hypertension, and ALND. However, all the participants in this study underwent level I/II ALND, making it impossible to gauge the role ALND played in severe lymphedema. Hence, we opted to use the data of the number of positive lymph nodes and total lymph node dissection, and interpectoral lymph nodes (IPNs) dissection in order to accurately and spatially reflect the damage to the patient’s lymphatic system and identify the association between them and the risk of severe lymphedema.

Identification of severe lymphedema

Lymphedema was defined as symptomatic arm swelling with a difference of 2 cm or more the circumference at two adjacent points between the affected and contralateral arms[14]. Specifically, circumference of both arms is measured 5 cm apart from each other with reference to the elbow flexion. The maximum value of the difference in arm circumference is used as the diagnostic result. Non-severe and severe arm lymphedema was defined as having a circumference difference of 2 to 4 cm and more than 4 cm, respectively, in the the forearm at any measurement site.

Statistical analysis

All statistical analyses were executed using SPSS version 25.0 software (IBM, Armonk, USA) and R software version 4.2.0 ( A binary logistic regression model was applied to identify and examine risk factors for severe lymphoedema. A forest plot was employed to display the odds ratios (ORs) (95% confidence interval [CI]) and p values of each variable. The candidate variables associated with severe lymphoedema with significance (p values < 0.05) were tested in a multivariable logistic regression model in the training cohort. A nomogram incorporating risk factors was created to predict the likelihood of severe BCRL and validated internally by bootstrapping and externally in the validation cohort. The calibration curve was plotted to observe the predictive performance of the nomogram. Patients from the retrospective cohort were divided into three risk groups (low, medium, and high risk) based on the first and third quartile of probabilities from the nomogram model. An unpaired t-test was used to compare the risk scores between the non-severe patients and severe patients. All p-values were two-sided and p-value < 0.05 was regarded as significant.


Characteristics of the eligible patients

This retrospective cohort enrolled 326 patients with BCRL, with a median (interquartile range) age of 48 (43–57) years. The median (interquartile range) tumor size, positive lymph nodes, total lymph node dissection, serum cholesterol, and BMI were 20 (5–30), 2(0–4), 18 (15–22), 5.107 (4.315–5.869), and 24.53 (22.43–26.86), respectively. IPNs dissection was performed in 18.4% (60/326) of the patients. Most of patients (92.3%) underwent chemotherapy, while 71.8% received radiotherapy, The median (interquartile range) circle of chemotherapy was 6 (4–8). Docetaxel was administered to 278 (85.3%) patients, while only 32.5% received neoadjuvant chemotherapy. In addition, 62.6% of the patients had a high educational level. In terms of marker genes, the expressions of ER, PR, Ki-67 and HER-2 were 66.3%, 56.1%, 50.3%, and 30%, respectively. Based on the diagnostic criteria, 235 and 91 patients were assigned to the non-severe lymphedema and severe lymphedema cohort, respectively. The initial characteristics of the cohort are presented in Table 1.

Table 1 Characteristics of BCRL patients in the retrospective cohort

Risk factors for severe lymphedema

A univariate logistic regression analysis was performed to identify predictive indicators associated with severe lymphedema, and the forestplot was generated to illustrate the OR and P-value of each variable (Fig. 1). Results revealed that age, IPNs dissection, positive lymph nodes, docetaxel treatment, radiotherapy, and education level were significantly associated with the severity of lymphedema (p < 0.05). Multivariable analysis suggested that all predictive factors (p < 0.05) from univariate analysis were significantly associated with the severity of lymphedema (Table 2), except for radiotherapy. Specifically, significant predictors were age (OR, 1.04; 95% CI, 1.01–1.07; p = 0.02), IPNs dissection (OR, 7.76; 95% CI, 3.87–15.54; p < 0.01), positive lymph nodes (OR, 1.06; 95% CI, 1.00−1.13, p = 0.03994), and education level (OR, 0.41; 95% CI, 0.23–0.73; p < 0.01).

Fig. 1
figure 1

The forestplot of the odd ratios (OR) of each variables for severe lyphedema

Table 2 Remaining predictors of the nomogram model after backward elimination for the prediction of severity of BCRL

Development and validation of the BCRL nomogram

As shown in Fig. 2A, a nomogram was constructed by integrating age, IPNs dissection, positive lymph nodes, and education level. To reclassify the retrospective cohort, we applied two cut-off values (0.0876 and 0.3498,) to divide the cohort into the low-, medium- and high-risk probabilities groups. The model was internally evaluated through 1000 bootstrapped samples and the calibration curve displayed predicted and actual probabilities. The C-index of the calibration curve in the internal calibration was 0.810 (Fig. 2B), while the C-index of the calibration curve for the validation set was 0.681 (Fig. 2C). Moreover, the risk probabilities in the severe cohort was significantly higher than that in the non-severe cohort (Fig. 2D, p < 0.001).

Fig. 2
figure 2

Severe-illness risk nomogram and triage tool for clinicians. (A) The nomogram integrating age, IPNs, positive lymph nodes, and education level was constructed to predict the 3-year risk probability of severe lymphedema (B) the calibration curve of internally validation with bootstrapping for the nomogram model. (C) the calibration curve for the nomogram model in the validation cohort. (D) Distribution of risk probability in the non-severe and severe lymphedema. *** p < 0.001


Breast cancer-related lymphedema is one of the most feared complications of post-surgery breast cancer survivors. Patients suffering from lymphedema frequently report a lower quality of life, poorer mobility, reduced self-esteem, coupled with an increased a higher risk of infection [16, 17]. Severe lymphedema is challenging to manage, has a higher risk of recurrence and progression, and requires long-term follow-up and monitoring. Identifying risk factors is crucial, as it aids physicians in recognizing high-risk patients and offering early interventions to prevent disease progression. A deeper understanding of risk factors can also lead to more effective treatment options. Despite the considerable evidence that has been collected regarding the risk factors for the development of lymphedema, the predictive indicators for severe lymphedema remain poorly understood. Therefore, this study examined, both individually and in combination, intraoperative or preoperative characteristics in BCRL patients in order to identify factors related to severe lymphedema and to develop a nomogram for assessing the severity of the lymphedema within 3 years of surgery. The results of this study revealed that advanced age, IPNs dissection, positive lymph nodes, and low education level were associated with an increased risk of developing severe lymphedema. IPNs dissection, in particular, had a greater influence on the development of severe lymphedema than the other risk factors. The nomogram, which integrated age, IPNs dissection, positive lymph nodes, and education level, showed a moderate performance in predicting the severity of lymphedema three years following surgery. Thus, this nomogram can be considered a useful tool for risk assessment and triage of the severity of lymphedema within 3 years of surgery.

Recent research highlighted a series of risk factors associated with lymphedema, including ALND, BMI, radiotherapy, age, chemotherapy, and the number of cycles of chemotherapy [15, 24, 25]. Chemotherapy may influence the inflammatory response and immunological status of cancer survivors, resulting in negative impacts on the normal operation of the lymphatic system [26]. It was suggetsed that BMI at BCRL diagnosis was the major risk factor associated with severe lymphedema [27]. However, findings from this study showed no significant association between BMI, chemotherapy, the number of cycles of chemotherapy and the severity of lymphedema. We hypothesize that sustained risk factors may determine the risk of developing severe lymph edema, since the negative impacts of BMI, radiotherapy, and chemotherapy can be reversed in subsequent in-hospital treatments, whereas age, educational level, and impaired lymphatic system are irreversible. A meta-analysis of 7 studies depicted that older patients were prone to suffer from severe forms of BCRL, yet the exact cause and effect relationship remains unclear [28]. In has been suggested that impaired contractility, increased permeability and immune cell dysfunction related to aging may explain the faster deterioration seen in older women [29]. Furthermore, this study also highlighted the importance of exploring a patient’s understanding of their disease and treatment options, as lower education levels have been linked to higher risk of severe lymphedema. Previously, Fu et al. demonstrated that BCRL patients with a lower education level were more likely to develop severe symptoms at 12 months post-surgery [30, 31].

It has been demonstrated that the incidence of lymphedema was highest in patients with thirty or more lymph nodes removed and increased with the number of positive nodes [21, 24, 32]. However, the association between the number of positive lymph nodes and the development of severe lymphedema remains unclear. Our study revealed that a larger number of positive nodes contribute to a higher risk of severe lymphedema, even though we did not find an association between total lymph node dissection and severe lymphedema. Generally, the more lymph nodes that are dissected, the more severely impaired lymph flow is. Nevertheless, it appears to be related to the location of the lymph nodes, as evidenced by the contribution of IPN to lymphedema. Thus, further investigations are necessary to delineate the exact role that the number of lymph nodes plays in the development of severe lymphedema. It is possible that lymphatic blockage from tumoral infiltration of the lymph node may be responsible for the slight increase in the risk of severe lymphedema by positive lymph nodes.

Notably, our data revealed that IPNs dissection had a considerable influence on the severity of lymphedema, which had not been addressed by previous studies focusing on BCRL risk factors. These findings suggest that IPNs dissection may be a crucial independent risk factor for the onset of lymphedema, which warrants further validation. IPNs, also referred to as Rotter’s nodes, located between pectoralis major and minor, are one of the lymphatic drainage pathways in breast cancer with a metastatic rate of only 4-9.9% [33]. At present, there is an ongoing discussion regarding whether routinely conducting IPNs dissection has any prospective prognostic or therapeutic benefits despite the recommendation from National Comprehensive Cancer Network (NCCN) in their guidelines [34]. Removal of interpectoral lymphatic tissue can lead to injury of the pectoral nerves and vessels, resulting in muscle atrophy and shoulder pain [35]. Our data further showed the contribution of IPNs removal to the development of severe lymphedema. Therefore, these data suggest that greater importance should be placed on IPN dissection and its inclusion in postoperative lymphatic management. For patients with pN0/N1 breast cancer, IPN clearance can be safely omitted even when modified radical mastectomy (MRM) breast conservation surgery is performed [36].

Our study has several limitations that should be considered. Firstly, our identification of risk factors of severe lymphedema was based on an limited regional retrospective database, which may not take into account potential ethnic or regional differences. Secondly, the internal validation of the results, which was conducted using bootstrapping, was limited by the small number of cases in the retrospective cohort. It would be preferable to validate the findings in external cohorts or prospective cohorts. Thirdly, our study only looked into the contribution of intraoperative clinical and laboratory indicators to severe lymphedema, while postoperative prevention and intervention are essential to the occurrence and development of the condition. Finally, due to the retrospective nature of our study, some risk factors associated with lymphedema were likely not included due to incomplete/unavailable data, which could limit the applicability of the nomogram. Thus, further research is required to combine the intraoperative and postoperative indicators to predict the development of severe lymphedema. Despite these limitations, we believe that the findings of this study are usable in terms of severe lymphedema prevention and further intervention globally.


In summary, we determined that age, IPNs dissection, positive lymph nodes, and education level were independent risk factors of severe lymphedema, with IPNs dissection having the most significant effect on the development of severe BCRL. These findings could be of use for the formulation of lymphedema surveillance strategies and the instruction of patients in clinical practice. Additionally, a nomogram incorporating age, IPNs dissection, positive lymph nodes, and education level was devised, which may be applied to conveniently evaluate the risk of severe lymphedema in patients undergoing surgery with ALND. Notwithstanding, further investigations in larger, multi-center, and prospective cohorts are necessary to validate these findings.

Data availability

All data generated or analyzed during this study are included in this published article.



Breast cancer-related lymphedema


axillary lymph node dissection


body mass index


interpectoral lymph nodes


estrogen receptor


progesterone receptor


human epidermal growth factor receptor 2


odd ratios


concordance index


National Comprehensive Cancer Network


modified radical mastectomy


  1. Ridner SH. Pathophysiology of lymphedema. SEMIN ONCOL NURS. 2013;29(1):4–11.

    Article  PubMed  Google Scholar 

  2. Mortimer PS. The pathophysiology of lymphedema. CANCER-AM CANCER SOC. 1998;83(12 Suppl American):2798–802.

    CAS  Google Scholar 

  3. Fu MR, Ridner SH, Hu SH, Stewart BR, Cormier JN, Armer JM. Psychosocial impact of lymphedema: a systematic review of literature from 2004 to 2011. Psycho-oncology. 2013;22(7):1466–84.

    Article  PubMed  Google Scholar 

  4. Shah C, Vicini FA. Breast cancer-related arm lymphedema: incidence rates, diagnostic techniques, optimal management and risk reduction strategies. INT J RADIAT ONCOL. 2011;81(4):907–14.

    Article  Google Scholar 

  5. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. LANCET ONCOL. 2013;14(6):500–15.

    Article  PubMed  Google Scholar 

  6. Deutsch M, Land S, Begovic M, Sharif S. The incidence of arm edema in women with breast cancer randomized on the National Surgical adjuvant breast and Bowel Project study B-04 to radical mastectomy versus total mastectomy and radiotherapy versus total mastectomy alone. INT J RADIAT ONCOL. 2008;70(4):1020–4.

    Article  Google Scholar 

  7. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981–22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. LANCET ONCOL. 2014;15(12):1303–10.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Feldman S, Bansil H, Ascherman J, Grant R, Borden B, Henderson P, Ojo A, Taback B, Chen M, Ananthakrishnan P, et al. Single Institution experience with lymphatic Microsurgical Preventive Healing Approach (LYMPHA) for the primary Prevention of Lymphedema. ANN SURG ONCOL. 2015;22(10):3296–301.

    Article  PubMed  Google Scholar 

  9. Ezzo J, Manheimer E, McNeely ML, Howell DM, Weiss R, Johansson KI, Bao T, Bily L, Tuppo CM, Williams AF et al. Manual lymphatic drainage for lymphedema following breast cancer treatment. COCHRANE DB SYST REV 2015(5):D3475.

  10. Dayan JH, Ly CL, Kataru RP, Mehrara BJ. Lymphedema: Pathogenesis and Novel Therapies. ANNU REV MED. 2018;69:263–76.

    Article  CAS  PubMed  Google Scholar 

  11. Kim M, Shin KH, Jung SY, Lee S, Kang HS, Lee ES, Chung SH, Kim YJ, Kim TH, Cho KH. Identification of prognostic risk factors for transient and persistent Lymphedema after Multimodal treatment for breast Cancer. CANCER RES TREAT. 2016;48(4):1330–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Byun HK, Chang JS, Im SH, Kirova YM, Arsene-Henry A, Choi SH, Cho YU, Park HS, Kim JY, Suh CO, et al. Risk of Lymphedema following contemporary treatment for breast Cancer: an analysis of 7617 consecutive patients from a multidisciplinary perspective. ANN SURG. 2021;274(1):170–8.

    Article  PubMed  Google Scholar 

  13. Zou L, Liu FH, Shen PP, Hu Y, Liu XQ, Xu YY, Pen QL, Wang B, Zhu YQ, Tian Y. The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: a 2-year follow-up prospective cohort study. BREAST CANCER-TOKYO. 2018;25(3):309–14.

    Article  Google Scholar 

  14. Coen JJ, Taghian AG, Kachnic LA, Assaad SI, Powell SN. Risk of lymphedema after regional nodal irradiation with breast conservation therapy. INT J RADIAT ONCOL. 2003;55(5):1209–15.

    Article  Google Scholar 

  15. De Groef A, Van Kampen M, Tieto E, Schönweger P, Christiaens MR, Neven P, Geraerts I, Gebruers N, Devoogdt N. Arm lymphoedema and upper limb impairments in sentinel node-negative breast cancer patients: a one year follow-up study. Breast. 2016;29:102–8.

    Article  PubMed  Google Scholar 

  16. Hidding JT, Beurskens CH, van der Wees PJ, van Laarhoven HW, Nijhuis-van DSM. Treatment related impairments in arm and shoulder in patients with breast cancer: a systematic review. PLoS ONE. 2014;9(5):e96748.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jørgensen MG, Toyserkani NM, Sørensen JA. The effect of prophylactic lymphovenous anastomosis and shunts for preventing cancer-related lymphedema: a systematic review and meta-analysis. MICROSURG. 2018;38(5):576–85.

    Article  Google Scholar 

  18. Penn IW, Chang YC, Chuang E, Chen CM, Chung CF, Kuo CY, Chuang TY. Risk factors and prediction model for persistent breast-cancer-related lymphedema: a 5-year cohort study. SUPPORT CARE CANCER. 2019;27(3):991–1000.

    Article  PubMed  Google Scholar 

  19. McLaughlin SA, Brunelle CL, Taghian A. Breast Cancer-related Lymphedema: risk factors, screening, management, and the impact of Locoregional Treatment. J CLIN ONCOL. 2020;38(20):2341–50.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Liu YF, Liu JE, Zhu Y, Mak YW, Qiu H, Liu LH, Yang SS, Chen SH. Development and validation of a nomogram to predict the risk of breast cancer-related lymphedema among chinese breast cancer survivors. SUPPORT CARE CANCER. 2021;29(9):5435–45.

    Article  PubMed  Google Scholar 

  21. Armer JM, Ballman KV, McCall L, Ostby PL, Zagar E, Kuerer HM, Hunt KK, Boughey JC. Factors Associated with Lymphedema in Women with node-positive breast Cancer treated with Neoadjuvant Chemotherapy and Axillary Dissection. JAMA SURG. 2019;154(9):800–9.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Aoishi Y, Oura S, Nishiguchi H, Hirai Y, Miyasaka M, Kawaji M, Shima A, Nishimura Y. Risk factors for breast cancer-related lymphedema: correlation with docetaxel administration. BREAST CANCER-TOKYO. 2020;27(5):929–37.

    Article  Google Scholar 

  23. Konishi T, Tanabe M, Michihata N, Matsui H, Nishioka K, Fushimi K, Seto Y, Yasunaga H. Risk factors for arm lymphedema following breast cancer surgery: a japanese nationwide database study of 84,022 patients. BREAST CANCER-TOKYO. 2023;30(1):36–45.

    Article  Google Scholar 

  24. Iyigun ZE, Duymaz T, Ilgun AS, Alco G, Ordu C, Sarsenov D, Aydin AE, Celebi FE, Izci F, Eralp Y, et al. Preoperative lymphedema-related risk factors in early-stage breast Cancer. LYMPHAT RES BIOL. 2018;16(1):28–35.

    Article  PubMed  Google Scholar 

  25. Voss RK, Cromwell KD, Chiang YJ, Armer JM, Ross MI, Lee JE, Gershenwald JE, Stewart BR, Shaitelman SF, Cormier JN. The long-term risk of upper-extremity lymphedema is two-fold higher in breast cancer patients than in melanoma patients. J SURG ONCOL. 2015;112(8):834–40.

    Article  PubMed  PubMed Central  Google Scholar 

  26. van der Willik KD, Koppelmans V, Hauptmann M, Compter A, Ikram MA, Schagen SB. Inflammation markers and cognitive performance in breast cancer survivors 20 years after completion of chemotherapy: a cohort study. BREAST CANCER RES. 2018;20(1):135.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Leray H, Malloizel-Delaunay J, Lusque A, Chantalat E, Bouglon L, Chollet C, Chaput B, Garmy-Susini B, Yannoutsos A, Vaysse C. Body Mass Index as a major risk factor for severe breast Cancer-related Lymphedema. LYMPHAT RES BIOL. 2020;18(6):510–6.

    Article  CAS  PubMed  Google Scholar 

  28. Guliyeva G, Huayllani MT, Boczar D, Avila FR, Forte AJ. Correlation of older age with severity of lymphedema in breast cancer survivors: a systematic review. Breast Dis. 2021;40(3):191–7.

    Article  CAS  PubMed  Google Scholar 

  29. Shang T, Liang J, Kapron CM, Liu J. Pathophysiology of aged lymphatic vessels. Aging. 2019;11(16):6602–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fu MR, Aouizerat BE, Yu G, Conley Y, Axelrod D, Guth AA, Gagner JP, Qiu JM, Zagzag D. Model-based patterns of Lymphedema Symptomatology: phenotypic and Biomarker characterization. CURR BREAST CANCER R. 2021;13(1):1–18.

    Article  CAS  Google Scholar 

  31. Fahradyan A, El-Sabawi B, Patel KM. Understanding patient expectations of Lymphedema surgery. PLAST RECONSTR SURG. 2018;141(6):1550–7.

    Article  CAS  PubMed  Google Scholar 

  32. Golshan M, Smith B. Prevention and management of arm lymphedema in the patient with breast cancer. J Support Oncol. 2006;4(8):381–6.

    PubMed  Google Scholar 

  33. Zhou X, Yang JX, Liu XY, Zhu NS, Jiang GL. Interpectoral nodes metastases in breast cancer. Chin J CANCER RES. 2008;20(3):202–4.

    Article  Google Scholar 

  34. Bale A, Gardner B, Shende M, Fromowitz F. Can interpectoral nodes be sentinel nodes? AM J SURG. 1999;178(5):360–1.

    Article  CAS  PubMed  Google Scholar 

  35. Fregnani JHTG, Macéa JR. Lymphatic drainage of the breast: from Theory to Surgical Practice. Int J Morphology. 2009;27:873–8.

    Article  Google Scholar 

  36. Yan Y, Jiang L, Fang J, Dai Y, Chenyu X, Ding J. Interpectoral Lymph Node Dissection can be spared in pN0/N1 invasive breast Cancer undergoing modified radical mastectomy: Single-Institution experience from Mainland China. CANCER MANAG RES. 2021;13:5855–63.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


Not applicable.


This study was supported by Medical and Health Science and Technology Project of Zhejiang Province (2023KY505;2023KY046). Traditional Chinese Medicine Science and technology Project of Zhejiang Province (2023ZL273)

Author information

Authors and Affiliations



XZL and YFL formulated the idea of the article and supervised the research. XZL, KWS, HJY, LLX, and YFL performed the research, analyzed the data and wrote the manuscript. KFL, XLM and YFL participated in revising the data and improving manuscript writing. All authors reviewed the manuscript, and all authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Yongfeng Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was conducted in accordance with the principles of the Declaration of Helsinki,and the study protocol was approved by the ethics committee of Zhejiang Provincial People’s Hospital. Ethics committee of Zhejiang Cancer Hospital waived the need for informed consent due to retrospective nature of the study.

Consent for publication

Not applicable..

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Sun, K., Yang, H. et al. Risk factors for the development of severe breast cancer-related lymphedema: a retrospective cohort study. BMC Cancer 23, 361 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: