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

doi:10.21203/rs.3.rs-2595690/v1

Download PDF

Research Article

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

https://doi.org/10.21203/rs.3.rs-2595690/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

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.

Breast cancer

lymphedema

Risk factors

ALND

neoadjuvant chemotherapy.

Breast cancer survival rates have increased significantly in recent decades due to improvements in screening and advances in multidisciplinary treatment [1]. Therefore, maintaining the quality of life and controlling treatment-related complications in long-term survivors has become an important goal [2–5]. Lymphedema is a common comorbidity of the upper extremity secondary to breast cancer treatment that occurs in approximately 22% of survivors [6]. Moreover, several reports have shown that BCRL may occur between initial treatment and 20 years after surgery, although most cases occur within 3 years [7]. BCRL occurs when protein-rich fluid accumulates in the soft tissues caused by an interruption of lymphatic flow, which negatively affects the patient's quality of life, both physically and psychosocially [8, 9].

Current data suggest that the development of BCRL is multifactorial and influenced by three categories of factors. Disease and treatment-related factors such as tumor size, ALND surgery, chemotherapy and radiotherapy, as well as lifestyle factors such as physical activity, body mass index (BMI) and preventive behaviors, and demographic factors such as monthly income, marital status, and ethnicity [8, 10–15]. However, in addition to the well-known risk factors, our group has recently identified two independent risk factors that have rarely been reported before: postoperative sleeping position and duration of drainage.

Neoadjuvant chemotherapy (NAC) is increasingly used in treating breast cancer because of its ability to downstage the primary tumor in the breast and the metastatic axillary lymph node [16]. However, NAC has recently been recognized as an independent risk factor for BCRL [17]. On the other hand, the advent of sentinel lymph node biopsy (SLNB) has resulted in lower lymphoedema rates by avoiding unnecessary ALND [18]. But ALND remains the standard of axillary surgery in patients with clinically positive lymph nodes or metastatic sentinel nodes [19]. Therefore, Women who have undergone NAC and surgery of ALND are at significant risk of developing lymphoedema. However, few studies have simultaneously investigated the demographic, disease and treatment-related and lifestyle factors that predict the development of BCRL for this subset of patients.

Breast cancer survivors who have been provided with BCRL information have significantly reduced symptoms and increased knowledge of BCRL [20]. In clinical practice, nurses play an essential role in raising awareness of lymphedema among patients. Therefore, this study was carried out to identify potential risk factors for the occurrence of BCRL in breast cancer patients who received NAC and ALND to optimize lymphedema surveillance and improve patient education on BCRL.

Eligibility criteria

This cohort study enrolled 356 newly diagnosed breast cancer patients who had undergone primary breast cancer surgery from June 2015 to June 2020 at Fujian Medical University's Union Hospital. The inclusion criteria were as follows: (1) 18 years of age or older, (2) cT0-T4N1-3M0 breast cancer, (3) Data are available at baseline and at least one post-operative follow-up time point, (4) Received NAC and subsequent ALND surgery. Exclusion criteria were as follows: (1) bilateral breast cancer (n = 3), (2) existing arm edema before surgery (n = 2), (3) lack of follow-up data (n = 2), (4) presence of severe cardiac or renal disease (n = 2), (5) local or systemic recurrence of breast cancer (n = 2). Finally, all 336 patients who received NAC and subsequent breast surgery and ALND were successfully included in the cohort. Figure 1 presents the flowchart of recruitment process. The hospital ethics committee approved the protocol, and informed consent was obtained from all study patients.

Measurement and assessment of lymphedema

The diagnosis of breast cancer-related lymphedema was made by objective measurement of limb circumference. Measurements were obtained at the following time points: before surgery (after completion of neoadjuvant chemotherapy) (baseline), 2 weeks after surgery, and 1, 3, 6, 12, 18, 24 and 30 months after surgery. The professionally trained nurse measured the limb circumference of both arms with flexible tape at four anatomical locations: (1) metacarpal, (2) wrist, (3) 10 cm below the lateral condyle, and (4) 10 cm above the lateral condyle, with the patient in a standing position with the elbow extended and the forearm in fore-flexion.

The patient was diagnosed with BCRL if the affected arm's circumference was > 3 cm at ≥ 1 anatomic location, compared to baseline and the contralateral arm. The formula for calculating the increase in arm circumference: (ipsilateral time point value - ipsilateral baseline value) - (contralateral time point value - contralateral baseline value). The time to develop BCRL was calculated from the date of the defined breast surgery to the date of diagnosis of BCRL.

Statistical analysis

The purpose of this analysis was to evaluate the risk factors related to lymphedema. Categorical variables were expressed as the number of patients (%). Differences between the two groups were tested by the χ2 and Fisher’s exact tests. The cumulative risk of different factors was generated using univariate logistic regression analysis. Risk factors associated with the development of lymphedema were analyzed using univariate logistic regression, ignoring the interference of other factors. Factors with p < 0.1 were considered statistically significant and then included in multivariate logistic regression. After adjusting for the effects of other factors, multivariate logistic regression was used to determine risk factors statistically correlated with the development of lymphedema. A statistically significant difference was defined as a p-value of less than 0.05. Point estimates (e.g., percentage of patients, hazard ratio (HR) and 95% confidence interval(CI)) were used to summarize variables and correlations. ALL statistical analysis was conducted using SPSS software version 25.

This study involved 336 patients with unilateral breast cancer and, 147 (43.75%) patients had BCRL. The comparison of demographics, clinical and lifestyle characteristics between BCRL and non-BCRL cohorts is present in Table 1. Patients with BCRL showed higher BMI, more positive lymph nodes and more lymph nodes removed, and were more likely to undergo radiotherapy and longer NAC treatment than those without BCRL. In addition, there were also significant differences in the following variables: occupation, home care, TNM staging, duration of drainage and postoperative drainage volume.

Table 1

Baseline Characteristics by Status. ª
	Non-BCRL group (n = 187)	BCRL group (n = 149)
Characteristic	Non-BCRL group (n = 187)	BCRL group (n = 149)	P Value
Age,y
< 50 ≥ 50	89 (47.6) 98 (52.4)	63 (52.4) 86 (57.7)	0.331
BMI category
< 24	121 (64.7)	72 (48.3)	0.003
≥ 24	66 (35.3)	77 (51.7)	0.003
Education level
University	42 (22.5)	21 (14.1)	0.131
Secondary school	78 (41.7)	65 (43.6)
Elementary school and below	67 (35.8)	63 (42.3)
Pressure sleeve
Yes	45 (24.1)	32 (21.5)	0.575
No	142 (75.9)	117 (78.5)	0.575
Rehabilitation exercise
Yes	80 (42.8)	56 (37.6)	0.335
No	107 (57.2)	93 (62.4)	0.335
Monthly income, RMB
< 3000	109 (58.3%)	90 (60.4%)	0.695
≥ 3000	78 (41.7%)	59 (39.6%)	0.695
Occupation
Light physical labor	67 (35.8)	49 (32.9)	0.003
Medium physical labor	68 (36.4)	33 (22.1)
Heavy physical labor	20 (10.7)	20 (13.4)
Others	32 (17.1)	47 (31.5)
Home care
Spouse	104 (55.6)	88 (59.1)	0.027
Children	64 (34.2)	39 (26.2)
Others	18 (9.8)	14 (9.4)
No	1 (0.5)	8 (5.4)
Operative side
Left	87 (46.5)	69 (66.3)	0.969
Right	100 (53.5)	80 (53.7)	0.969
Type of surgery
Mastectomy	172 (92.0)	142 (95.3)	0.221
BCS	15 (8.0)	7 (4.7)	0.221
Anatomical location
Upper-inner quadrant	31 (16.6)	25 (16.8)	0.517
Lower-inner quadrant	10 (5.3)	7 (4.7)
Upper-outer quadrant	103 (55.1)	93 (62.4)
Lower-outer quadrant	27 (14.4)	13 (8.7)
Central Quadrant	16 (8.6)	11 (7.4)
TNM stage
YPCR	4 (2.1)	1 (0.7)	0.001
I	7 (3.7)	1 (0.7)
II	128 (68.4)	80 (53.7)
III	47 (25.1)	66 (44.3)
IV	1 (0.5)	1 (0.7)
Total nodes removed
≤ 15	70 (37.4)	27 (18.1)	< 0.001
> 15	117 (62.6)	122 (81.9)	< 0.001
Total positive nodes
0	4 (2.1)	2 (1.3)	0.006
1–3	133 (71.1)	83 (55.7)
≥ 4	50 (26.7)	64 (43.0)
Radiotherapy
Yes	99 (52.9)	108 (72.5)	<0.001
No	88 (47.1)	41 (27.5)	<0.001
Endocrine therapy regimen
No	72 (38.5)	72 (48.3)	0.101
SERM	17 (9.1)	7 (4.7)
AI	98 (52.4)	70 (47)
Neoadjuvant chemotherapy regimen
Taxane-containing regimen	62 (33.2)	42 (28.2)	0.068
Anthracycline-containing regimen	9 (4.8)	8 (5.4)
Anthracycline- and taxane-containing regimen	98 (52.4)	94 (63.1)
Others	18 (9.6)	5 (3.4)
Duration of NAC,d
< 105	51 (27.3)	14 (9.4)	< 0.001
105–143	50 (26.7)	54 (36.2)
> 143	86 (46.0)	81 (54.4)
Duration of Drainage ,d
< 10	6 (3.2)	8 (5.4)	< 0.001
10–19	129 (69.0)	79 (53.0)
20–29	31(16.6)	55(36.9)
> 29	21(11.2)	7(4.7)
Postoperative sleeping position
Biased to the healthy side	49 (26.2)	31 (20.8)	< 0.001
Biased to the surgery side	7 (3.7)	32 (21.5)
Lied flat	42 (22.5)	32 (21.5)
Alternated	89 (47.6)	54 (36.2)
Postoperative drainage volume,ml
< 200	121 (64.7)	79 (53.0)	0.030
≥ 200	66 (35.3)	70 (47.0)	0.030
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); HR, hazard ratio; NAC, neoadjuvant chemotherapy. SERM, selective estrogen receptor modulator; AI, aromatase inhibitor; TNM, Tumor Node Metastasis.
ªData are presented as number(percentage) of patients.

In the univariate analysis, ten factors were correlated with the development of BCRL and were included in the multivariate analysis (Table 2). The multivariate analysis identified five factors as independent predictors of BCRL (P < 0.05). (1) The BCRL rates significantly increased concerning the total lymph nodes removed > 15 (HR = 1.593; P = 0.036). (2) Radiotherapy was associated with a higher rate of BCRL (HR = 1.611; P = 0.020). (3) The BCRL rates were lower among patients who received NAC for 105 days or shorter (HR = 0.471; P = 0.020). (4) Women with drainage for 20–29 days were found to be at significantly increased risk of developing BCRL (HR = 1.568; P = 0.028). (5) The HR of BCRL for the postoperative sleeping position (biased to the surgery side versus Biased to the healthy side) was 2.033 with P = 0.019. However, after adjusting for other variables, BMI, postoperative drainage volume, home care, total positive nodes and endocrine therapy were not statistically significant in multivariate analysis.

Table 2

**Univariate and multivariate analyses of risk factors associated with lymphedema.ª**
Variable	HR (95%CI)	P Value
Univariable Analysis
Age,y
< 50	1 [Reference]
≥ 50	1.195 (0.863–1.654)	0.283
BMI category
< 24	1 [Reference]
≥ 24	1.502 (1.089–2.072)	0.013
Home care
No	1 [Reference]
Spouse	0.380 (0.183–0.787)	0.009
Children	0.301 (0.140–0.647)	0.002
Others	0.359 (0.150–0.858)	0.021
Total lymph nodes removed
≤ 15	1 [Reference]
> 15	1.935 (1.275–2.936)	0.002
Total positive lymph nodes
0	0.516 (0.126–2.106)	0.356
1–3	0.604 (0.436–0.838)	0.002
≥ 4	1 [Reference]
Radiotherapy received
No	1 [Reference]
Yes	1.806 (1.261–2.589)	0.001
TNM stage
YPCR	1 [Reference]
I	0.693 (0.043–11.077)	0.795
II	2.277 (0.317–16.368)	0.413
III	3.883 (0.539–27.984)	0.178
IV	3.368 (0.211–53.872)	0.391
Duration of NAC, d
< 105	0.347 (0.193–0.625)	< 0.001
105–143	1 [Reference]
≥ 144	0.851 (0.603–1.202)	0.360
Duration of Drainage, d
< 10	1.553 (0.750–3.213)	0.236
10–19	1 [Reference]
20–29	2.077 (1.470–2.935)	< 0.001
> 29	0.653 (0.301–1.415)	0.280
Postoperative sleeping position
Biased to the healthy side	1 [Reference]
Biased to the surgery side	3.027 (1.836–4.989)	< 0.001
Lied flat	1.244 (0.759–2.039)	0.386
Alternated	0.974 (0.626–1.515)	0.908
Postoperative drainage volume, ml
< 200	1 [Reference]
≥ 200	1.420 (1.029–1.960)	0.033
Endocrine therapy
No	1 [Reference]
SERM	0.515 (0.237–1.119)	0.094
AI	0.790 (0.568–1.097)	0.159
Neoadjuvant chemotherapy regimen
Taxane-containing regimen	1 [Reference]
Anthracycline-containing regimen	1.189 (0.558–2.533)	0.653
Anthracycline- and taxane-containing regimen	1.155 (0.803–1.662)	0.437
Others	0.467 (0.185–1.179)	0.107
Multivariable Analysis
Total lymph nodes removed
≤ 15	1 [Reference]
> 15	1.593 (1.031–2.463)	0.036
Radiotherapy received
No	1 [Reference]
Yes	1.611 (1.079–2.406)	0.020
Duration of NAC,d
< 105	0.471 (0.249–0.890)	0.020
105–143	1 [Reference]
≥ 144	0.724 (0.498–1.051)	0.090
Duration of Drainage ,d
< 10	1.896 (0.896–4.014)	0.094
10–19	1 [Reference]
20–29	1.568 (1.049–2.345)	0.028
> 29	0.685 (0.310–1.514)	0.350
Postoperative sleeping position
Biased to the healthy side	1[Reference]
Biased to the surgery side	2.033(1.124–3.677)	0.019
Lied flat	1.171(0.705–1.946)	0.542
Alternated	1.044(0.729–1.495)	0.817
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); HR, hazard ratio; NAC, neoadjuvant chemotherapy; SERM, selective estrogen receptor modulator; AI, aromatase inhibitor.
ªData are presented as number(percentage) of patients.

The 2.5-year cumulative risk of BCRL according to the five independent risk factors that were found to be significantly different in both univariate and multivariate analyses (radiotherapy, total lymph nodes removed, duration of NAC, duration of drainage and postoperative sleeping position) were presented in Fig. 2.

The aim of this study was to explore potential risk factors for the development of BCRL in breast cancer patients who received NAC and ALND. In our study, we identified five independent risk factors: radiotherapy, duration of NAC, number of lymph nodes removed, duration of drainage, and postoperative sleeping position. Our study has a large number of patient data and an adequately followed-up period; we believe our research could bring more credible evidence to change management strategies and patient care.

Placement of a closed-suction drain in the mastectomy site and axilla after breast cancer surgery is to decrease postoperative complications, particularly seroma formation [21–23]. However, in our study, we found that Patients with a longer duration of drainage were at higher risk of BCRL. Likewise, Saadet et al. stated that the long duration of the axillary drain was a risk factor for BCRL (P = 0.045) [24]. Two reasons may explain this phenomenon. Firstly, a longer duration of drainage reflects a higher degree of lymphatic vessel damage, supporting that more extensive axillary surgery increases the incidence of BCRL [25]. Secondly, Patients with drainage tubes need to immobilize the affected limb to reduce drainage[26]. However, carrying the drainage tube for a long time can lead to stiffness in the arm and inevitably, the optimal time for post-operative rehabilitation exercises is missed. A cross-sectional study of 766 patients showed that women who exercised their affected arm decreased the risk of developing BCRL through a potential mechanism called “muscle pump” [12].

A meta-analysis reported that the decision to remove drainage based on the amount of drainage would reduce the incidence of seroma, an independent risk factor for lymphedema [27], compared to short-term removal of drainage [28]. However, due to management regarding drain placement, the number of drains, and hospitalization varying widely between breast units [29], there are no widely applicable criteria for the removal of drainage. Therefore, future multicenter and larger cohort studies based on uniform criteria are required to better understand the relationship between drainage time and BCRL.

The relationship between postoperative sleeping position and BCRL has never been studied before. Our study found that sleeping biased towards the affected arm significantly increased the incidence of BCRL (HR = 3.027). Prolonged compression of the affected limb impedes the return of lymphatic fluid, disrupting the morphology and function of the lymphatic system and ultimately leading to BCRL. Besides, prolonged compression of the limb leads to ischemia of the subcutaneous tissues, causing a reduction in subcutaneous fat and muscle atrophy, which further affects the functional recovery of the lymphatics. Patients often consciously avoid putting pressure on the affected arm in the early postoperative period. However, later in life, they may think they have recovered from breast cancer and may unconsciously sleep on the affected side. This result demonstrates that some breast cancer survivors are under-aware of BCRL, highlighting the importance of correcting postoperative sleep position.

The association between radiotherapy and BCRL is well documented in the literature [30–33]. In our study, patients who received radiotherapy were 1.8 times more likely to develop BCRL than those who did not. A retrospective study of 7617 patients showed patients with more extensive radiation fields were at greater risk of lymphedema; compared with no radiation or breast/chest wall radiation alone, regional lymph node irradiation (RNI) increased the risk of BCRL by 2–4 times [31]. In addition, similarly, the total lymph nodes removed is another well-known independent risk factor for BCRL [6, 8, 34, 35]. Hwa Kyung Byun et al. reported that the 3-year cumulative BCRL rates were 3.0%, 10.0%, 20.2%, and 24.4% in patients with 0 to 5, 6 to 10, 11 to 15, and > 15 lymph nodes removed, respectively (P < 0.001) [31]. Interestingly, several reports suggest that the combination of ALND and radiotherapy has a synergistic effect on the development of BCRL [8, 32, 33]. However, The relationship between radiotherapy regimens and the number of lymph nodes removed has rarely been studied, which may be helpful in developing individualized radiotherapy regimens for breast cancer patients receiving axillary dissection to reduce the incidence of BCRL.

In recent years, increasing attention has focused on studying the risk factors for BCRL in the NAC setting. Giacomo Montagna et al. found that NAC was an independent risk factor for BCRL (OR = 2.10 ; 95%CI = 1.16–3.95 ; P = 0.01) [36]. Our study suggests that lower incidence of BCRL in patients with shorter duration NAC, which is in line with a study reporting that the longer NAC duration was correlated with increased BCRL incidence [17]. In general, there are two possible factors contributing to this result. Firstly, the number of cycles of chemotherapy infusion in the ipsilateral arm was reported as an independent risk factor for developing BCRL by Jose´ Luiz B. Bevilacqua et al. [37]. Secondly, regarding the specific toxicity of chemotherapy agents, many studies showed that taxane-based chemotherapy could result in BCRL by increasing extracellular fluid accumulation [38–40]. Therefore, more attention should be paid to patients with longer duration of NAC and treated with taxane-based chemotherapy.

The limitations of this study were as follows: Firstly, in our study, BCRL was diagnosed by objective measures only, lacking a subjective approach, which may have contributed to missing some potential patients. However, according to a meta-analysis, objective measures are the most used diagnostic criteria for lymphedema [41]. What’s more, we only considered whether radiotherapy was administered and did not analyze the impact of different chemotherapy regimens. But there have been many studies showing that RNI is associated with a higher risk of developing BCRL than radiation to the breast or chest wall alone [31, 33, 41]. In addition, a strength of our study is that we collected uniform bilateral arm measurements at several time points up to 30 months, including pre-surgical measurement, to reduce the impact of the patient's initial body size differences.

In conclusion, our research showed that more than 40% of breast cancer patients who received NAC and ALND suffered BCRL. We identified five independent risk factors associated with the development of BCRL: radiotherapy, duration of NAC, number of lymph nodes removed, duration of drainage, and postoperative sleeping position. Healthcare workers should focus on monitoring patients with one or more of these factors to enable early detection and intervention. Further research is needed to investigate the effects of drainage time and sleep position on the development of BCRL.

Acknowledgements

The authors thank all of the women who participated in the study and the assistance of Fujian Medical University's Union Hospital.

Author contribution

Conceptualization: YJL, CGS and JQF. Data collection: LJH, LQB, ZDL and WJJ. Data analysis: RLC and YSY. Writing-original draft preparation: RLC and YSY. Writing-review and editing: RLC and JZ. All authors read and approved the final manuscript.

Funding

This study was funded by the Fujian Provincial Department of Finance (2022CZ003).

Ethics approval

All research procedures involving human participants comply with the ethical standards of the institution and/or the National Research Council, which follows the ethical guidelines of the 1975 Declaration of Helsinki.

Consent to participate

Informed consent was obtained from all of the participants in this study.

Consent to publish

Not applicable.

Conflict of interest

The authors declare no competing interests.

DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, Jemal A, Siegel RL (2019) Breast cancer statistics, 2019 CA Cancer J Clin 69: 438-451
Bakar Y, Tugral A, Uyeturk U (2018) Measurement of Local Tissue Water in Patients with Breast Cancer-Related Lymphedema Lymphat Res Biol 16: 160-164
Khan F, Amatya B, Pallant JF, Rajapaksa I (2012) Factors associated with long-term functional outcomes and psychological sequelae in women after breast cancer Breast 21: 314-320
Rief W, Bardwell WA, Dimsdale JE, Natarajan L, Flatt SW, Pierce JP (2011) Long-term course of pain in breast cancer survivors: a 4-year longitudinal study Breast Cancer Res Treat 130: 579-586
Ahmed RL, Prizment A, Lazovich D, Schmitz KH, Folsom AR (2008) Lymphedema and quality of life in breast cancer survivors: the Iowa Women's Health Study J Clin Oncol 26: 5689-5696
Shen A, Lu Q, Fu X, Wei X, Zhang L, Bian J, Qiang W, Pang D (2022) Risk factors of unilateral breast cancer-related lymphedema: an updated systematic review and meta-analysis of 84 cohort studies Support Care Cancer 31: 18
Petrek JA, Senie RT, Peters M, Rosen PP (2001) Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis Cancer 92: 1368-1377
Kim M, Kim SW, Lee SU, Lee NK, Jung SY, Kim TH, Lee ES, Kang HS, Shin KH (2013) A model to estimate the risk of breast cancer-related lymphedema: combinations of treatment-related factors of the number of dissected axillary nodes, adjuvant chemotherapy, and radiation therapy Int J Radiat Oncol Biol Phys 86: 498-503
Chachaj A, Malyszczak K, Pyszel K, Lukas J, Tarkowski R, Pudelko M, Andrzejak R, Szuba A (2010) Physical and psychological impairments of women with upper limb lymphedema following breast cancer treatment Psychooncology 19: 299-305
DiSipio T, Rye S, Newman B, Hayes S (2013) Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis Lancet Oncol 14: 500-515
Cormier JN, Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM (2010) Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema Cancer 116: 5138-5149
Liu YF, Liu JE, Zhu Y, Mak YW, Qiu H, Liu LH, Yang SS, Chen SH (2021) Development and validation of a nomogram to predict the risk of breast cancer-related lymphedema among Chinese breast cancer survivors Support Care Cancer 29: 5435-5445
Jung SY, Shin KH, Kim M, Chung SH, Lee S, Kang HS, Lee ES, Kwon Y, Lee KS, Park IH, Ro J (2014) Treatment factors affecting breast cancer-related lymphedema after systemic chemotherapy and radiotherapy in stage II/III breast cancer patients Breast Cancer Res Treat 148: 91-98
Leysen L, Beckwee D, Nijs J, Pas R, Bilterys T, Vermeir S, Adriaenssens N (2017) Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis Support Care Cancer 25: 3607-3643
Rockson SG (2018) Lymphedema after Breast Cancer Treatment N Engl J Med 379: 1937-1944
Wang H, Mao X (2020) Evaluation of the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer Drug Des Devel Ther 14: 2423-2433
Armer JM, Ballman KV, McCall L, Ostby PL, Zagar E, Kuerer HM, Hunt KK, Boughey JC (2019) Factors Associated With Lymphedema in Women With Node-Positive Breast Cancer Treated With Neoadjuvant Chemotherapy and Axillary Dissection JAMA Surg 154: 800-809
Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M (2017) Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial JAMA 318: 918-926
Wilke LG, McCall LM, Posther KE, Whitworth PW, Reintgen DS, Leitch AM, Gabram SG, Lucci A, Cox CE, Hunt KK, Herndon JE, 2nd, Giuliano AE (2006) Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial Ann Surg Oncol 13: 491-500
Fu MR, Chen CM, Haber J, Guth AA, Axelrod D (2010) The effect of providing information about lymphedema on the cognitive and symptom outcomes of breast cancer survivors Ann Surg Oncol 17: 1847-1853
Oertli D, Laffer U, Haberthuer F, Kreuter U, Harder F (1994) Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer Br J Surg 81: 856-859
Troost MS, Kempees CJ, de Roos MAJ (2015) Breast cancer surgery without drains: no influence on seroma formation Int J Surg 13: 170-174
Talbot ML, Magarey CJ (2002) Reduced use of drains following axillary lymphadenectomy for breast cancer ANZ J Surg 72: 488-490
Ugur S, Arici C, Yaprak M, Mesci A, Arici GA, Dolay K, Ozmen V (2013) Risk factors of breast cancer-related lymphedema Lymphat Res Biol 11: 72-75
Goldberg JI, Wiechmann LI, Riedel ER, Morrow M, Van Zee KJ (2010) Morbidity of sentinel node biopsy in breast cancer: the relationship between the number of excised lymph nodes and lymphedema Ann Surg Oncol 17: 3278-3286
Browse DJ, Goble D, Jones PA (1996) Axillary node clearance: who wants to immobilize the shoulder? Eur J Surg Oncol 22: 569-570
Toyserkani NM, Jorgensen MG, Haugaard K, Sorensen JA (2017) Seroma indicates increased risk of lymphedema following breast cancer treatment: A retrospective cohort study Breast 32: 102-104
Droeser RA, Frey DM, Oertli D, Kopelman D, Baas-Vrancken Peeters MJ, Giuliano AE, Dalberg K, Kallam R, Nordmann A (2009) Volume-controlled vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery: a meta-analysis Breast 18: 109-114
Gupta R, Pate K, Varshney S, Goddard J, Royle GT (2001) A comparison of 5-day and 8-day drainage following mastectomy and axillary clearance Eur J Surg Oncol 27: 26-30
Konishi T, Tanabe M, Michihata N, Matsui H, Nishioka K, Fushimi K, Seto Y, Yasunaga H (2023) Risk factors for arm lymphedema following breast cancer surgery: a Japanese nationwide database study of 84,022 patients Breast Cancer 30: 36-45
Byun HK, Chang JS, Im SH, Kirova YM, Arsene-Henry A, Choi SH, Cho YU, Park HS, Kim JY, Suh CO, Keum KC, Sohn JH, Kim GM, Lee IJ, Kim JW, Kim YB (2021) Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective Ann Surg 274: 170-178
Gross JP, Whelan TJ, Parulekar WR, Chen BE, Rademaker AW, Helenowski IB, Donnelly ED, Strauss JB (2019) Development and Validation of a Nomogram to Predict Lymphedema After Axillary Surgery and Radiation Therapy in Women With Breast Cancer From the NCIC CTG MA.20 Randomized Trial Int J Radiat Oncol Biol Phys 105: 165-173
Nguyen TT, Hoskin TL, Habermann EB, Cheville AL, Boughey JC (2017) Breast Cancer-Related Lymphedema Risk is Related to Multidisciplinary Treatment and Not Surgery Alone: Results from a Large Cohort Study Ann Surg Oncol 24: 2972-2980
Kilbreath SL, Refshauge KM, Beith JM, Ward LC, Ung OA, Dylke ES, French JR, Yee J, Koelmeyer L, Gaitatzis K (2016) Risk factors for lymphoedema in women with breast cancer: A large prospective cohort Breast 28: 29-36
Togawa K, Ma H, Sullivan-Halley J, Neuhouser ML, Imayama I, Baumgartner KB, Smith AW, Alfano CM, McTiernan A, Ballard-Barbash R, Bernstein L (2014) Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study Breast Cancer Res 16: 414
Montagna G, Zhang J, Sevilimedu V, Charyn J, Abbate K, Gomez EA, Mehrara B, Morrow M, Barrio AV (2022) Risk Factors and Racial and Ethnic Disparities in Patients With Breast Cancer-Related Lymphedema JAMA Oncol 8: 1195-1200
Bevilacqua JL, Kattan MW, Changhong Y, Koifman S, Mattos IE, Koifman RJ, Bergmann A (2012) Nomograms for predicting the risk of arm lymphedema after axillary dissection in breast cancer Ann Surg Oncol 19: 2580-2589
Penn IW, Chang YC, Chuang E, Chen CM, Chung CF, Kuo CY, Chuang TY (2019) Risk factors and prediction model for persistent breast-cancer-related lymphedema: a 5-year cohort study Support Care Cancer 27: 991-1000
Aoishi Y, Oura S, Nishiguchi H, Hirai Y, Miyasaka M, Kawaji M, Shima A, Nishimura Y (2020) Risk factors for breast cancer-related lymphedema: correlation with docetaxel administration Breast Cancer 27: 929-937
Swaroop MN, Ferguson CM, Horick NK, Skolny MN, Miller CL, Jammallo LS, Brunelle CL, O'Toole JA, Isakoff SJ, Specht MC, Taghian AG (2015) Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort Breast Cancer Res Treat 151: 393-403
Sanniyasi E, Patrick APR, Rajagopalan K, Gopal RK, Damodharan R (2022) Characterization and in vitro anticancer potential of exopolysaccharide extracted from a freshwater diatom Nitzschia palea (Kutz.) W.Sm. 1856 Sci Rep 12: 22114

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

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

Status:

Version 1

Abstract

Figures

Introduction

Methods

Eligibility criteria

Measurement and assessment of lymphedema

Statistical analysis

Result

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1