Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients

Konishi, Takaaki; Tanabe, Masahiko; Michihata, Nobuaki; Matsui, Hiroki; Nishioka, Koki; Fushimi, Kiyohide; Seto, Yasuyuki; Yasunaga, Hideo

doi:10.1007/s12282-022-01395-5

Cited by 7 publications

(8 citation statements)

References 40 publications

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“…The association between radiotherapy and BCRL is well documented in the literature [30][31][32][33]. In our study, patients who received radiotherapy were 1.8 times more likely to develop BCRL than those who did not.…”

Section: Discussionsupporting

confidence: 62%

Factors affecting lymphedema after neoadjuvant chemotherapy and axillary dissection in female breast cancer patients: A retrospective cohort study based on the Chinese population

Chen

et al. 2023

Preprint

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Purpose Breast cancer-related lymphedema (BCRL) is a common complication in breast cancer survivors. Most BCRL studies have focused on patients receiving adjuvant chemotherapy, and relatively little attention has been paid to BCRL in patients with neoadjuvant chemotherapy (NAC). This study aimed to investigate the risk factors associated with BCRL in Chinese women undergoing NAC and axillary lymph node dissection (ALND). Methods In our institution, this cohort study collected data from 336 women with clinically node-positive breast cancer who received NAC and ALND surgery from 2015 to 2020. The BCRL was assessed by objective measurement of limb circumference. Multivariate logistic regression was used to determine risk factors for BCRL, including clinical, demographic and lifestyle-related characteristics. Results The cumulative incidence of BCRL within 2.5 years was 43.75%. The factors independently associated with BCRL were radiotherapy (versus no radiotherapy; hazard ratio [HR]=1.611; P=0.020), NAC for 105 days or shorter (versus NAC for 105-143 days; HR=0.471; P=0.020), >15 lymph nodes removed (versus ≤15 lymph nodes removed; HR=1.593; P=0.036 ), drainage for 20-29 days (versus drainage for 10-19 days; HR=1.568; P=0.028), and sleeping biased toward affected arm (versus sleeping biased toward healthy arm; HR=2.033; P=0.019). Conclusion This study identified several risk factors for BCRL in breast cancer patients after NAC and ALND. Patients with one or more of these factors should be monitored carefully for early detection and intervention. Further research is needed to investigate the effects of drainage time and sleep position on the development of BCRL.

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Section: Discussionsupporting

confidence: 62%

Factors affecting lymphedema after neoadjuvant chemotherapy and axillary dissection in female breast cancer patients: A retrospective cohort study based on the Chinese population

Chen

et al. 2023

Preprint

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Section: Discussionmentioning

confidence: 99%

“…At least 13 BCRL predictive models have been published (eTable 4 in Supplement 1), although all have at least 1 conceptual issue that inhibits functionality. In addition to inclusion of data points that are not readily available, omission of SLNB, and diagnoses based on patient-reported symptoms, some studies define lymphedema based on retrospective identification via ICD - 9 or ICD - 10 diagnosis codes or treatment associated with lymphedema, both of which introduce bias. Specifically, models based on ICD -defined cohorts of patients with lymphedema may include patients with mild or subclinical lymphedema; this may explain the relatively low sensitivity of our preoperative model (38.7%)—a model that was trained on a cohort with a more stringent definition of lymphedema—when validated with an ICD -based cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Some models have favorable predictive ability, as measured by the area under the receiver operating characteristic curve (AUC), but include variables that are not readily available in a preoperative and/or postoperative setting; these variables include radiation field and fractionation type, number of cycles of chemotherapy in the ipsilateral arm, chemotherapeutic agent, proportion of lymph flow above the level of the axillary vein, mammographic breast density, and number of lymph nodes removed or positive nodes . Many models neglect or have a low AUC on external validation . An additional problem is the omission of sentinel lymph node biopsy (SLNB) from nearly all models, despite de-escalation of axillary surgery following the ACOSOG Z0011 and AMAROS trials, increasing rates of SLNB, and an approximate 5% to 6% rate of lymphedema after SLNB .…”

Section: Introductionmentioning

confidence: 99%

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Feasibility and Clinical Utility of Prediction Models for Breast Cancer–Related Lymphedema Incorporating Racial Differences in Disease Incidence

et al. 2023

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ImportanceBreast cancer–related lymphedema (BCRL) is a common complication of axillary lymph node dissection (ALND) but can also develop after sentinel lymph node biopsy (SLNB). Several models have been developed to predict the risk of disease development before and after surgery; however, these models have shortcomings that include the omission of race, inclusion of variables that are not readily available to patients, low sensitivity or specificity, and lack of risk assessment for patients treated with SLNB.ObjectiveTo create simple and accurate prediction models for BCRL that can be used to estimate preoperative or postoperative risk.Design, Setting, and ParticipantsIn this prognostic study, women with breast cancer who underwent ALND or SLNB from 1999 to 2020 at Memorial Sloan Kettering Cancer Center and the Mayo Clinic were included. Data were analyzed from September to December 2022.Main Outcomes and MeasuresDiagnosis of lymphedema based on measurements. Two predictive models were formulated via logistic regression: a preoperative model (model 1) and a postoperative model (model 2). Model 1 was externally validated using a cohort of 34 438 patients with an International Classification of Diseases diagnosis of breast cancer.ResultsOf 1882 included patients, all were female, and the mean (SD) age was 55.6 (12.2) years; 80 patients (4.3%) were Asian, 190 (10.1%) were Black, 1558 (82.8%) were White, and 54 (2.9%) were another race (including American Indian and Alaska Native, other race, patient refused to disclose, or unknown). A total of 218 patients (11.6%) were diagnosed with BCRL at a mean (SD) follow-up of 3.9 (1.8) years. The BCRL rate was significantly higher among Black women (42 of 190 [22.1%]) compared with all other races (Asian, 10 of 80 [12.5%]; White, 158 of 1558 [10.1%]; other race, 8 of 54 [14.8%]; P &lt; .001). Model 1 included age, weight, height, race, ALND/SLNB status, any radiation therapy, and any chemotherapy. Model 2 included age, weight, race, ALND/SLNB status, any chemotherapy, and patient-reported arm swelling. Accuracy was 73.0% for model 1 (sensitivity, 76.6%; specificity, 72.5%; area under the receiver operating characteristic curve [AUC], 0.78; 95% CI, 0.75-0.81) at a cutoff of 0.18, and accuracy was 81.1% for model 2 (sensitivity, 78.0%; specificity, 81.5%; AUC, 0.86; 95% CI, 0.83-0.88) at a cutoff of 0.10. Both models demonstrated high AUCs on external (model 1: 0.75; 95% CI, 0.74-0.76) or internal (model 2: 0.82; 95% CI, 0.79-0.85) validation.Conclusions and RelevanceIn this study, preoperative and postoperative prediction models for BCRL were highly accurate and clinically relevant tools comprised of accessible inputs and underscored the effects of racial differences on BCRL risk. The preoperative model identified high-risk patients who require close monitoring or preventative measures. The postoperative model can be used for screening of high-risk patients, thus decreasing the need for frequent clinic visits and arm volume measurements.

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“…Only those potential predictors with prior clinical knowledge were selected for consideration[ 19 – 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.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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

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Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients

Cited by 7 publications

References 40 publications

Factors affecting lymphedema after neoadjuvant chemotherapy and axillary dissection in female breast cancer patients: A retrospective cohort study based on the Chinese population

Factors affecting lymphedema after neoadjuvant chemotherapy and axillary dissection in female breast cancer patients: A retrospective cohort study based on the Chinese population

Feasibility and Clinical Utility of Prediction Models for Breast Cancer–Related Lymphedema Incorporating Racial Differences in Disease Incidence

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

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