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Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT.In a cohort of 11,982 BC patients diagnosed in 1998-2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events.Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94-1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98-1.01, P = .68).Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

AIMS: The aim of TROG 14.04 was to assess the feasibility of deep inspiration breath hold (DIBH) and its impact on radiation dose to the heart in patients with left-sided breast cancer undergoing radiotherapy. Secondary end points pertained to patient anxiety and cost of delivering a DIBH programme. MATERIALS AND METHODS: The study comprised two groups - left-sided breast cancer patients engaging DIBH and right-sided breast cancer patients using free breathing through radiotherapy. The primary end point was the feasibility of DIBH, defined as left-sided breast cancer patients' ability to breath hold for 15 s, decrease in heart dose in DIBH compared with the free breathing treatment plan and reproducibility of radiotherapy delivery using mid-lung distance (MLD) assessed on electronic portal imaging as the surrogate. The time required for treatment delivery, patient-reported outcomes and resource requirement were compared between the groups. RESULTS: Between February and November 2018, 32 left-sided and 30 right-sided breast cancer patients from six radiotherapy centres were enrolled. Two left-sided breast cancer patients did not undergo DIBH (one treated in free breathing as per investigator choice, one withdrawn). The mean heart dose was reduced from 2.8 Gy (free breathing) to 1.5 Gy (DIBH). Set-up reproducibility in the first week of treatment assessed by MLD was 1.88 ± 1.04 mm (average ± 1 standard deviation) for DIBH and 1.59 ± 0.93 mm for free breathing patients. Using a reproducibility cut-off for MLD of 2 mm (1 standard deviation) as per study protocol, DIBH was feasible for 67% of DIBH patients. Radiotherapy delivery using DIBH took about 2 min longer than for free breathing. Anxiety was not significantly different in DIBH patients and decreased over the course of treatment in both groups. CONCLUSION: Although DIBH was shown to require about 2 min longer per treatment slot, it has the potential to reduce heart dose in left-sided breast cancer patients by nearly a half, provided careful assessment of breath hold reproducibility is carried out.

Although global heart dose has been associated with late cardiac toxic effects in patients who received radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructure dosimetry are limited. We investigated whether dose to the left anterior descending artery (LAD) correlates with adverse cardiac events.We identified 375 consecutively treated female patients from 2012 to 2018 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses (LAD DMedian follow-up time was 48 months. Thirty-six patients experienced a cardiac event, and 23 patients experienced a major cardiac event. On univariate and multivariable analyses, increased LAD DDose to the LAD correlated with adverse cardiac events in this cohort. Contouring and minimizing dose to the LAD should be considered for patients receiving radiation therapy for left-sided breast cancer.

Our purpose was to investigate the interfraction and intrafraction reproducibility and practical applicability of continuous positive airway pressure (CPAP) for left breast volumetric modulated arc therapy (VMAT).Interfraction reproducibility of the position of the heart was evaluated by measuring the heart-to-target distance on 20 planning computed tomography (CT) and 300 daily cone beam CT of 20 patients with left breast cancer treated with a 15-fraction VMAT. The dosimetric metrics of the whole heart and its substructures were compared between CPAP and free-breathing based VMAT plans. Intrafraction reproducibility was evaluated by measuring the motions of the breast target and diaphragm in 4-dimensional CT of 20 female patients with nonbreast cancer. Lastly, we analyzed the CPAP compliance data of 237 consecutive patients with left-sided breast cancer with and without internal mammary node irradiation (IMNI).The heart position was reproducible as evidenced by an absolute average heart-to-target distance error of 2.0 ± 2.0 mm. Compared with free-breathing, CPAP significantly reduced the mean heart dose and the dose to the left ventricle and left anterior descending artery. The average intrafraction position variation of the breast target was 0.5 ± 0.5, 2.5 ± 2.0, and 1.8 ± 1.4 mm in the mediolateral, craniocaudal, and anteroposterior directions, respectively. CPAP was successfully applied in 221 patients (93%), with a mean heart dose of 1.6 ± 0.7 Gy (IMNI: 2.0 Gy and no IMNI: 1.1 Gy).CPAP has adequate heart-sparing capability and sufficient reproducibility in VMAT for left-sided breast cancer treatment, with a high compliance rate. Thus, CPAP is applicable in routine practice for left-sided breast cancer radiation therapy.

Inclusion of the internal mammary chain in the radiotherapy target volume (IMC-RT) improves disease-free and overall survival in higher risk breast cancer patients, but increases radiation doses to heart and lungs. Dosimetric data show that either modified wide-tangential fields (WT) or volumetric modulated arc therapy (VMAT) together with [AQ1]voluntary deep inspiration breath hold (vDIBH) keep mean heart doses below 4 Gy in most patients. However, the impact on departmental resources has not yet been documented. This phase II clinical trial compared the time taken to deliver IMC-RT using either WT and vDIBH or VMAT and vDIBH, together with planning time, dosimetry, set-up reproducibility and toxicity.Left-sided breast cancer patients requiring IMC-RT were randomised to receive either WT(vDIBH) or VMAT radiotherapy. The primary outcome was treatment time, powered to detect a minimum difference of 75 min (5 min/fraction) between techniques. The population mean displacement, systematic error and random error for cone beam computed tomography chest wall matches in three directions of movement were calculated. Target volume and organ at risk doses were compared between groups. Side-effects, including skin (Radiation Therapy Oncology Group), lung and oesophageal toxicity (Common Terminology Criteria for Adverse Events v 4.03) rates, were compared between the groups over 3 months. Patient-reported outcome measures, including shoulder toxicity at baseline, 6 months and 1 year, were compared.Twenty-one patients were recruited from a single UK centre between February 2017 and January 2018. The mean (standard deviation) total treatment time per fraction for VMAT treatments was 13.2 min (1.7 min) compared with 28.1 min (3.3 min) for WT(vDIBH). There were no statistically significant differences in patient set-up errors in between groups. The average mean heart dose for WT(vDIBH) was 2.6 Gy compared with 3.4 Gy for VMAT(vDIBH) (P = 0.13). The mean ipsilateral lung VVMAT(vDIBH) and WT(vDIBH) are feasible options for locoregional breast radiotherapy including the IMC. VMAT improves nodal coverage and delivers treatment more quickly, resulting in less breath holds for the patient. This is at the cost of increased dose to some non-target tissues. The latter does not appear to translate into increased toxicity in this small study.

Cardiovascular toxicity from breast radiation therapy (RT) is a concern to patients and providers. Herein, we present a cardiac-sparing strategy using tangential volumetric modulated arc therapy (tVMAT) in comparison with standard 3-dimensional conformal RT. Ten patients with left-sided breast cancer previously treated with adjuvant RT covering the breast, as well as the axillary and supraclavicular nodal regions, were selected for the study. For each patient, 2 plans were created: a dual-isocenter 3-field 3-dimensional conformal RT plan and a monoisocentric tVMAT plan. The prescription for both techniques was 50 Gy in 25 fractions to the breast and nodal target volumes. Compared with 3-dimensional conformal RT, tVMAT provided more uniform coverage to the breast and regional lymph nodes (mean conformity index: 1.42 for tVMAT vs 2.42 for 3-dimensional conformal RT; P.01), and the maximum point dose for tVMAT was lower on average (112.8% for tVMAT vs 121.5% for 3-dimensional conformal RT; P.001). Coverage to the lymph nodes was superior for tVMAT (average minimum coverage to 95% of entire nodal target volumes: 99.5% of prescribed dose for tVMAT vs 94.9% for 3-dimensional conformal RT; P.001). Organ-at-risk sparing was improved with tVMAT, with a lower average V

To implement a semi-automatic planning technique for whole breast irradiation with two tangential IMRT fields and to test the produced dose distribution against clinical 3DCRT plans, for introducing the technique in clinical practice.The Auto-Planning module of the PinnacleA statistically significant improvement in target coverage and dose homogeneity was observed for autoIMRT. No statistically significant differences were observed for ipsilateral organs, except for the ipsilateral lung in left DIBH, where slightly lower DThe developed autoIMRT technique was proven to be advantageous for target coverage and homogeneity and sufficiently robust towards isocenter displacements. The use of automated planning consistently reduces the planning workload with improvements in plan quality.

Deep inspiratory breath-hold (DIBH) has become standard in radiotherapy for left-sided breast cancer to reduce the heart dose. This study evaluated breath-hold stability and reproducibility using Elekta's Active Breathing Coordinator™ (ABC) and its effectiveness and feasibility in left-sided breast cancer patients undergoing radiotherapy.Eligible patients were planned with free breathing (FB) and DIBH protocols. DIBH treatment was considered if the mean heart dose (MHD) was ≥2 Gy on the FB plan. Those who proceeded with DIBH treatment were enrolled for the pilot study. Electronic portal images of DIBH treatment beams were taken using the movie-exposure mode for breath-hold stability and reproducibility analysis. DIBH effectiveness in heart dose reduction and impact on simulation and treatment durations were compared with FB protocol.Out of 56 eligible patients, 15 proceeded with DIBH treatment. The mean difference of patient setup within a single breath-hold was 0.4 mm; between different breath-holds of the same beam 1.1 mm and between different days 2.6 mm. DIBH reduced the MHD by 47% and the mean left anterior descending artery (LAD) dose by 35%. DIBH took longer time than FB in simulation and treatment. At least 14% of the eligible patients did not tolerate DIBH during simulation.ABC leads to stable and reproducible breath-holds and results in significant heart dose reductions. It may not be tolerated by all patients and has resource implications.

Objective To investigate the clinicopathologic characteristics and outcome of bilateral breast cancer (BBC) in the Chinese population. Methods : A retrospective study was conducted on 7797 cases with primary breast cancer diagnosed between 2016 and 2020, including 7618 cases of unilateral breast cancer (UBC) and 179 cases of BBC. Among the latter, there were 108 cases of synchronous BBC (SBBC) and 71 cases of metachronous BBC (MBBC). We compared the clinicopathological characteristics and outcomes among these groups. Results : In the present study, the incidence of SBBC and MBBC are 1.39% and 0.91% among the general population, respectively. In comparison of UBC and BBC, SBBC and MBBC, there are significant differences in the common clinicopathological characteristics, such as pathologic stage, hormone receptor (HR) status and molecular type. Additionally, differences in the pathologic stage and the type of surgery in the first and second tumors are observed in both SBBC and MBBC. In respect of the surgical treatment of BBC, 49.72% of the patients chose mastectomy. The 3-year disease free survival (DFS) for SBBC and MBBC are 94.4% and 96.9%, respectively. There is no difference in the overall survival (OS) and DFS between SBBC and MBBC. The histological grade and type of surgery on tumors of both sides are important influencing factors of DFS in the BBC patients. Conclusion : There are statistical differences in the clinicopathological characteristics and outcomes between SBBC and MBBC among the Chinese population. Therefore, the treatment of BBC patients should be individualized.

Background Published treatment technique comparisons for postoperative left-sided whole breast irradiation (WBI) with deep-inspiration breath-hold (DIBH) are scarce, small, and inconclusive. In this study, fully automated multi-criterial plan optimization, generating a single high-quality, Pareto-optimal plan per patient and treatment technique, was used to compare for a large patient cohort 1) intensity modulated radiotherapy (IMRT) with two tangential fields and 2) volumetric modulated arc therapy (VMAT) with two small tangential subarcs. Materials and methods Forty-eight randomly selected patients recently treated with DIBH and 16 × 2.66 Gy were included. The optimizer was configured for the clinical planning protocol. Comparisons between IMRT and VMAT included dosimetric plan parameters, estimated excess relative risks (ERR) for toxicities, delivery times, MUs, and deliverability accuracy at a linac. Results The automatically generated IMRT and VMAT plans applied in this study were similar or higher in quality than the manually generated clinical plans. For equal PTVin V95% (98.4 ± 0.9%), VMAT had significant advantages compared to IMRT regarding breast dose homogeneity and doses in heart and ipsilateral lung, at the cost of some minor deteriorations for contralateral breast (few cases with larger deteriorations) and lung. Conformality improved from 1.38 to 1.18 (p Conclusion For WBI in conservative therapy of left-sided breast patients treated with DIBH, VMAT with two tangential subarcs was generally dosimetrically superior to IMRT with two tangential static fields. Results need confirmation by robustness analyses.

We aimed to compare dosimetric parameters between three-dimensional conformal radiation therapy followed by electron beam boost (3D-CRT + EB) and volumetric modulated arc therapy using simultaneous integrated boost (SIB-VMAT) in left-sided breast cancer patients.This study included 57 patients with left-sided breast cancer who underwent SIB-VMAT. All patients had a computed tomography-based maximum heart distance of ≥ 1 cm and were prescribed a dose of 42.56 Gy/16 fractions to the planning target volume and a concomitant-boosted target dose of 53.2 Gy or 51.2 Gy. The 3D-CRT + EB plan was retrospectively created for the purpose of comparison using tangential fields with field-in-field technique followed by electron beam irradiation.The doses to the clinical target volume significantly improved in the SIB-VMAT plans. All dosimetric parameters for the left anterior descending coronary artery (LAD) and LAD middle position (LAD mid) in the SIB-VMAT plans were significantly lower than those for 3D-CRT + EB plans (P 0.01), while the doses to the heart, lung, contralateral breast and non-target tissue were decreased in the 3D-CRT + EB plans compared with those in the SIB-VMAT plans (e.g., 1.9 Gy vs. 2.9 Gy; P 0.001 for the mean dose of heart).SIB-VMAT significantly improved the dose to the target while reducing the doses to the LAD and LAD mid, whereas 3D-CRT + EB significantly decreased the doses to the heart and other organs at risk in patients with left-sided breast cancer at risk for radiation-induced coronary artery disease.

To analyse stereotactic biopsies of microcalcifications in patients with previous ipsilateral breast-conserving surgery (BCS) to identify the positivity rate, assess for an association between the patient's primary cancer or mammographic appearances of the microcalcifications, and the risk of recurrence.Relevant patients from 2018-2020 were identified via a retrospective review of the prospectively maintained radiological procedure database. Clinicopathological features of the patients' primary tumour and new calcifications were obtained from the hospital electronic patient record system and the national integrated medical imaging system.Thirty-one percent of recurrences post-ipsilateral BCS presented as isolated microcalcifications on mammography. Fifty-three percent of patients undergoing stereotactic biopsy of ipsilateral calcifications had recurrence. A positive margin status was associated with new or recurrent malignancy. There was no significant correlation between oestrogen-receptor status, sentinel lymph node status, adjuvant radiotherapy or chemotherapy and the risk of recurrence. Calcifications within the tumour bed were more likely to be benign while calcifications within the same quadrant but remote from the tumour bed were more likely malignant. All coarse calcifications were benign while 67% of fine linear/fine linear branching and 89% of fine pleomorphic calcifications were malignant.Increased time since diagnosis, positive margin status, fine pleomorphic and fine linear calcifications in the same quadrant as the tumour bed were associated with malignancy. Patients with coarse calcifications and calcifications within the tumour bed may avoid stereotactic biopsy and undergo short-interval surveillance.

In whole breast and regional nodal irradiation (WB + RNI), breathhold increases organ at risk (OAR) sparing. WB + RNI is usually performed in supine position, because positioning materials obstruct beam paths in prone position. Recent advancements allow prone WB + RNI (pWB + RNI) with increased sparing of OARs compared to supine WB + RNI. We evaluate positional and dosimetrical impact of repeated breathhold (RBH) and failure to breathhold (FTBH) in pWB + RNI. Twenty left-sided breast cancer patients were scanned twice in breathhold (baseline and RBH) and once free breathing (i.e. FTBH). Positional impact was evaluated using overlap index (OI) and Dice similarity coefficient (DSC). Dosimetrical impact was assessed by beam transposition from the baseline plan. Mean OI and DSC ranges were 0.01–0.98 and 0.01–0.92 for FTBH, and 0.73–1 and 0.69–1 for RBH. Dosimetric impact of RBH was negligible. FTBH significantly decreased minimal dose to CTV WBI, level II and the internal mammary nodes, with adequate mean doses. FTBH significantly increased heart, LAD, left lung and esophagus dose. OI and DSC for RBH and FTBH show reproducible large ROI positions. Small ROIs show poor overlap. FTBH maintained adequate target coverage but increased heart, LAD, ipsilateral lung and esophagus dose. RBH is a robust technique in pWB + RNI. (Clinicaltrials.gov: NCT05179161, registered 05/01/2022).

BACKGROUND Although deep inspiratory breath-hold (DIBH) is routinely used for left-sided breast cancers, its benefits for right-sided breast cancer (rBC) have yet to be established. We compared free-breathing (FB) and DIBH treatment plans for a cohort of rBC undergoing regional nodal irradiation (RNI) to determine its potential benefits. METHODS AND MATERIALS rBC patients considered for RNI (internal mammary nodal chains, supraclavicular field, with or without axilla) from October 2017 to May 2020 were included in this analysis. For each patient, FB versus DIBH plans were generated and dose volume histograms evaluated the following parameters: mean lung dose, ipsilateral lung V20/V5 (volumes of lung receiving 20 Gy and 5 Gy, respectively); mean heart dose and heart V5 (volumes of heart receiving 5 Gy); liver V20 absolute /V30 absolute (absolute volume of liver receiving 20 Gy and 30 Gy, respectively), liver Dmax, and total liver volume irradiated (TVIliver). The dosimetric parameters were compared using Wilcoxon signed-rank testing. RESULTS Fifty-four patients were eligible for analysis, comparing 108 FB and DIBH plans. DIBH significantly decreased all lung and liver parameters: mean lung dose (19.7 Gy-16.2 Gy, P < .001), lung V20 (40.7%-31.7%, P < .001), lung V5 (61.2%-54.5%, P < .001), TVIliver (1446 cc vs 1264 cc; P = .006) liver Dmax (50.2 Gy vs 48.9 Gy; P = .023), liver V20 (78.8-23.9 cc, P < .001), and liver V30 (58.1-14.6 cc, P < .001) compared with FB. DIBH use did not significantly improve heart parameters, although the V5Heart trended on significance (1.25-0.6, P = .067). CONCLUSIONS This is the largest cohort to date analyzing DIBH for RNI-rBC. Our findings demonstrate significant improvement in all lung and liver parameters with DIBH, supporting its routine consideration for rBC patients undergoing comprehensive RNI.

Breast with supraclavicular fossa (Br+SCF) radiotherapy treatments can utilise a monoisocentric technique to concurrently treat the breast area (tangent fields) and supraclavicular area (opposing fields). The region where these treatment areas adjoin is known as the junction region, field junction, or match line. Dose variations that may occur about the junction region, due to geometrical inaccuracies, are typically feathered out in patient free-breathing treatments. However, there is limited information on how dose at the junction is influenced in deep inspiration breath hold (DIBH) treatments. This study aims to investigate dose variation at the field junction for a patient population undertaking a DIBH Br+SCF treatment course. GAFChromic EBT3 film was used to record the dose across the junction at skin surface for approximately one third of the 25 fraction treatment course for 11 patients undergoing DIBH Br+SCF treatment. Single fraction and summated fraction profiles for each patient were compared to profiles in the treatment planning system and assessed the: (1) local dose variations, (2) position of the 50% dose gradient, and (3) relative dose at the nominal junction. Local dose variations of 10% or greater, position displacement of the junction greater than 5 mm, and relative dose differences at the match line greater than 10% can be found within single fraction dose profiles. When these single fractions are summed over the treatment course, the position variations reduce to 2 mm and dose variations reduced to within 10% for 10 of the 11 patients. Only one of 11 patients recorded a summed dose difference greater than ±10% over their treatment, recording 76% ± 8% of the planned dose in this region. This was due to a small overall position displacement of 1.8 ± 1.6 mm from the nominal junction. A feathering of the dose at the junction is present for DIBH Br+SCF patient treatments. The feathering effect is sufficient, in the majority of cases studied, to reduce any differences in dose and displacement present in single fractions. This work also demonstrates that there may be exceptions from this observed behavior that should be considered. Further study in this area using a larger patient cohort is recommended.

Background/Aim: Post-operative radiotherapy for breast cancer can increase cardiac disease in a dose-dependent manner. In this study we show the reduction of dose to heart and left anterior descending artery (LAD) which can be achieved by using “Deep inspiration breath-hold” (DIBH) technique. Patients and Methods: Tangential 3D-planned radiation was delivered to 357 patients with left-sided breast cancer, 159 of them with the DIBH technique. A distinction was made according to fractionation scheme. Results: The mean heart dose was significantly reduced by DIBH from 2.64 Gy to 1.39 Gy (p

BACKGROUND: Radiotherapy after breast surgery decreases locoregional recurrence and improves survival. This is not without risks from radiation exposure and could have implications in clinical practice. Our study investigates the correlation between tumour location and radiation dose to the heart. METHODS: Left-sided breast cancer patients who had radiotherapy at Aberdeen Royal Infirmary in 2010 were identified. Tumour location was established from notes and imaging. Radiotherapy planning scans were reviewed, and cardiac doses calculated. The mean cardiac dose, maximum dose and volume of the heart in the field, along with V5-V40, were determined. RESULTS: 40 patients had mastectomies and 118 breast conserving surgery. The median percentage of the heart in the field and the Interquartile Range was 0.59% (0.03–1.74) for all patients, with the highest for lower inner quadrant (LIQ) tumours 1.20% (0.29–2.40), followed by mastectomy 0.94% (0.02-1.82). The mean heart dose showed a higher median for mastectomies 1.59 Gy (1.00-1.94), followed by LIQ tumours 1.58 Gy (1.31–2.28), with an overall median of 1.42 Gy (1.13–1.95). The median percentage of the heart in the field, the mean cardiac dose and V5-V30 did not reach statistical significance, however, V40 and the maximum dose did. CONCLUSIONS: The benefits of radiotherapy after breast cancer surgery are established, but with potential harm from cardiac exposure. Our cohort showed higher radiation exposure to the heart in patients with LIQ tumours and mastectomies but reached significance only for V40 and maximum dose. This highlights tumour location as a potentially important risk factor for cardiac exposure with breast radiotherapy.

Background Non-coplanar volumetric modulated arc therapy (ncVMAT) is proposed to reduce toxicity in heart and lungs for locoregional radiotherapy of left-sided breast cancer, including internal mammary nodes (IMN). Patients and methods This retrospective study included 10 patients with left-sided breast cancer who underwent locoregional radiotherapy after breast-conserving surgery. For each patient, the ncVMAT plan was designed with four partial arcs comprising two coplanar arcs and two non-coplanar arcs, with a couch rotating to 90°. The prescribed dose was normalized to cover 95% of planning target volume (PTV), with 50 Gy delivered in 25 fractions. For each ncVMAT plan, dosimetric parameters were compared with the coplanar volumetric modulated arc therapy (coV-MAT) plan. Results T here were improvements in conformity index, homogeneity index and V55 of total target volume (PTVall) comparing ncVMAT to coVMAT (p < 0.001). Among the organs at risk, the average V30, V20, V10, V5, and mean dose (Dmean) of the heart decreased significantly (p < 0.001). Furthermore, ncVMAT significantly reduced the mean V20, V10, V5, and Dmean of left lung and the mean V10 and V5 and Dmean of contralateral lung (p < 0.001). An improved sparing of the left anterior descending coronary artery and right breast were also observed with ncVMAT (p < 0.001). Conclusions Compared to coVMAT, ncVMAT provides improved conformity and homogeneity of whole P TV, better dose sparing of the heart, bilateral lungs, left anterior descending coronary artery (LAD), and right breast for locoregional radiotherapy of left-sided breast cancer with IMN, potentially reducing the risk of normal tissue damage.

To review and update the incidence and risk factors for breast cancer-related lymphedema based on cohort studies.The study was guided by the Joanna Briggs Institute methodology and the Cochrane handbook for systematic reviews. PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, CNKI, SinoMed, and Wan Fang Database were searched from inception to November 15, 2021. Cohort studies reported adjusted risk factors were selected. PRISMA guideline was followed. Study quality were evaluated using the Newcastle-Ottawa scale. Random-effects models were adopted. The robustness of pooled estimates was validated by meta-regression and subgroup analysis. Lymphedema incidence and adjusted risk factors in the multivariable analyses with hazard / odds ratios and 95% CIs were recorded.Eighty-four cohort studies involving 58,358 breast cancer patients were included. The pooled incidence of lymphedema was 21.9% (95% CI, 19.8-24.0%). Fourteen factors were identified including ethnicity (black vs. white), higher body mass index, higher weight increase, hypertension, higher cancer stage (III vs. I-II), larger tumor size, mastectomy (vs. breast conservation surgery), axillary lymph nodes dissection, more lymph nodes dissected, higher level of lymph nodes dissection, chemotherapy, radiotherapy, surgery complications, and higher relative volume increase postoperatively. Additionally, breast reconstruction surgery, and adequate finance were found to play a protective role. However, other variables such as age, number of positive lymph nodes, and exercise were not correlated with risk of lymphedema.Treatment-related factors still leading the development of breast cancer-related lymphedema. Other factors such as postoperative weight increase and finance status also play a part. Our findings suggest the need to shift the focus from treatment-related factors to modifiable psycho-social-behavioral factors.