Arm Morbidity Research Articles

Financial Difficulty Over Time in Young Adults With Breast Cancer.

Young adults aged 18 to 39 years represent the minority of breast cancer diagnoses but are particularly vulnerable to financial hardship. Factors contributing to sustained financial hardship are unknown. To identify financial hardship patterns over time and characterize factors associated with discrete trajectories; it was hypothesized that treatment-related arm morbidity, a key source of expense, would be associated with long-term financial difficulty. This cohort study included US young adults aged 40 years or younger treated between 2006 and 2016. Eligible patients were treated for stage 0 to stage III breast cancer at institutions participating in the Young Women's Breast Cancer Study, which included a specialized cancer institute and 12 other academic and community hospitals. Patients who responded at baseline and returned a 1-year survey were included in analysis. Data were analyzed in March 2024. Trajectory modeling classified patterns of financial difficulty from baseline through 10 years postdiagnosis using the Cancer Rehabilitation Evaluation System (CARES) scale. Multinomial regression examined characteristics, including treatment-related arm morbidity, associated with each trajectory. A total 1008 patients were included (median [IQR] age at diagnosis, 36 [33-39] years; 60 Asian [6.0%], 35 Black [3.5%], 47 Hispanic [4.7%], 884 White [87.7%]); 840 patients were college graduates (83.3%), 764 were partnered at baseline (75.8%), 649 were nulliparous (64.4%), and 908 were without comorbidities at enrollment (90.1%). Patients' tumors were primarily stage I-II (778 [77.2%]), estrogen receptor/progesterone receptor-positive (754 [74.8%]), and ERBB2-negative (formerly HER2) (686 [68.1%]). Patients were more frequently treated with mastectomy than breast conservation (771 [76.5%] vs 297 [29.5%]; P < .001). A majority of patients received radiation therapy (627 [62.2%]), chemotherapy (760 [75.4%]), and endocrine therapy (610 [60.6%]). A total of 727 patients (72.1%) reported arm symptoms within 2 years of surgery. Three distinct trajectories of experiences with finances emerged: 551 patients (54.7%) had low financial difficulty (trajectory 1), 293 (29.1%) had mild difficulty that improved (trajectory 2), and 164 (16.3%) had moderate to severe difficulty peaking several years after diagnosis before improving (trajectory 3). Hispanic ethnicity (OR, 3.71; 95% CI, 1.47-9.36), unemployment at baseline and 1 year (OR, 2.66; 95% CI, 1.63-4.33), and arm symptoms (OR, 1.77; 95% CI, 1.06-2.96) were associated with increased odds of experiencing trajectory 3. Having a college degree (OR, 0.20; 95% CI, 0.12-0.34) or being partnered (OR, 0.24; 95% CI, 0.15-0.38) were associated with increased odds of experiencing trajectory 1. In this cohort study of young adults with breast cancer, we identified a subset of patients who experienced a high degree of financial difficulty persisting into early survivorship. Targeted interventions to mitigate financial toxicity-modifiable factors that include support for the employability or return to work support for those experiencing arm symptoms after treatment-are needed.

An associate of suspicious axillary node and sentinel node in breast cancer to minimizing axillary surgery, prospective cohort study

Background: Arm morbidity and postoperative complications following sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) are common problems in patients with breast cancer. The de-escalating axillary surgery is increasing; however, there is a lack of patients with suspicious nodes. This study aimed to reduce the need for SLNB in suspicious lymph node cases. Methods: A prospective cohort study of women with invasive breast cancer who underwent surgery between January 2021 and December 2022. The study included two cohorts: Cohort A comprised patients with stage cT1-2N0-1M0 cancer who planned upfront surgery, while Cohort B included patients with stages cT1-4N2M0, cT3-4N1M0, or cT1-2N0-1M0 who received neoadjuvant systemic treatment. During the study, a clip was inserted into the suspicious lymph node on imaging to determine whether it could serve as a sentinel node and potentially replace SLNB or reduce the need for axillary surgery. Result: In cohort A, twenty-two surgeries were performed, while in cohort B, seven surgeries were performed. The median follow-up time was 15 months. In cohort A, 71% of the patients had cN0 disease, while 28% had cN1 disease. A suspicious node correlated to a sentinel node was noted in 66.67% of cohort A. The false-negative rate (FNR) was 14.28%. However, when the clip node removal procedure was performed instead of the sentinel node procedure, the FNR was 10%. Conclusion: In early breast cancer, suspicious nodes in imaging studies could not currently represent sentinel lymph nodes, and the FNR was still high. Nevertheless, more studies with larger populations will provide a better understanding due to the limited number of patients.

Less Is (Sometimes) More: Laparoscopic Peritoneal Lavage and Drainage for Diverticulitis.

Introduction: Laparoscopic lavage and drainage (LLD) emerged as an alternative to Hartmann's procedure (HP) for patients with diverticulitis and uncontained perforation. Although initially popular as a less invasive approach, its use in modern practice is in question. This summary will review the available literature to show techniques, outcomes, and indications. Methods: The literature was reviewed for relevant case studies, randomized trials, prospective series, retrospective analyses, and meta-analyses to define peritoneal lavage and determine the clinical outcomes of peritoneal lavage. Results: LLD can be considered on an individual basis for Hinchey III diverticulitis (purulent peritonitis), but there are several contraindications. The extent of adhesionolysis (limited versus extensive) as well as the management of sites of perforation found during surgery are debated. Most surgeons continue lavage with warm saline until water runs clear and place drains in the operation. Three randomized controlled trials (RCTs), the LADIES, SCANDIV, and DILALA trials compared LLD with either resection and anastomosis or Hartmann's procedure. One other RCT (the LapLAND trial) is still with results pending. The LADIES trial studied LLD versus primary anastomosis and resection in Hinchey III diverticulitis and was terminated early secondary to higher 30-day morbidity in the LLD arm; however, 3-year data showed no significant difference in morbidity and mortality. The SCANDIV trial compared LLD with resection in acute diverticulitis (Hinchey I-III) and saw no difference in 90-day morbidity or mortality; however, it noted higher rates of reoperation in the LLD group. The DILALA trial compared Hinchey III diverticulitis patients undergoing LLD with open HP and found that the LLD group had a lower rate of reoperation at 2 years, but no difference in rates of readmission or mortality. Conclusions: Debate still remains over the technique of LLD and specific indications, as well as outcomes compared with resection and primary anastomosis or HP.

Quantifying the Impact of C7 Spinal Nerve Harvest on Spontaneous, Patient-Initiated Movement of the Donor Upper Extremity.

Transfer of a healthy C7 spinal nerve is a tool for upper extremity reanimation in patients with severe brachial plexus injury (BPI). Its use remains controversial owing to concern for neurological injury to the donor arm. Utilizing wearable motion-sensor technology, we aimed to quantify donor arm morbidity after C7 spinal nerve harvest in patients with pan-BPI, reporting both the time and magnitude of donor arm movement in a real-world setting compared to healthy controls. Seventeen patients who underwent contralateral C7 (CC7) transfer for traumatic pan-BPI at least 2 years prior were compared to 14 healthy controls. Each participant wore an accelerometer on both arms for 7 consecutive days. The vector time (VT), or time of movement measured in hours/day, and the vector magnitude (VM), or magnitude of arm movement measured as a single vector magnitude per second, were collected and compared between groups. The correlation between VT and VM and time from C7 spinal nerve harvest was also calculated. At mean 7.7 years after C7 spinal nerve harvest, there was no difference between donor and control arms for VT (5.76±1.55] vs 5.45±1.22 hours, P = 0.56) or VM (2242236±753853 vs 1919223±579723 activity counts, P = 0.20), regardless of donor arm dominance. The C7 harvest cohort used the injured arm 53% of the time and with 27% of the power of the donor arm. There was no significant difference in time or magnitude of arm movement between donor arms and the arms of healthy controls.

Prediction of High Nodal Burden in Patients With Sentinel Node–Positive Luminal ERBB2-Negative Breast Cancer

In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment. To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND. The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024. Predictors of high nodal burden. High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration. Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83). The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed. ClinicalTrials.gov Identifier: NCT02240472.

Completion axillary lymph node dissection for the identification of pN2–3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial

In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1-2, grade 1-2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1-T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1-2, histological grade 1-2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52-71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6-59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery. As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.

Arm morbidity and financial difficulty in breast cancer survivors.

Long-term upper extremity symptoms after breast cancer treatment may impact patient-reported financial difficulty. In this cross-sectional investigation, we hypothesized that severity of arm symptoms would be associated with greater financial difficulty. Stage 0-III breast cancer patients treated at our institution from 2002 to 2012 were recruited for a 2018 survey study appraising disease-specific patient-centered outcomes using EORTC-QLQ-BR23 and EORTC-QLQ-C30 questionnaires. The association between Arm Symptom (AS) score and Financial Impact (FI) score was assessed, adjusting for clinically relevant variables. Of 1126 interested participants, 882 (78%) responded to surveys. Three hundred fourteen (36%) with incomplete responses were excluded. Median time from surgery was 9years; 181 (32%) and 117 (21%) had mastectomy with or without reconstruction, 126 (22%) received postmastectomy radiation (PMRT), and 221 (39%) underwent axillary lymph node dissection. 76 (13%) reported some degree of financial difficulty; 10 (2%) the highest degree of difficulty. Of 217 (38%) patients experiencing arm symptoms, 60 (28%) had severe symptoms. Seven (70%) of those with highest degree of financial difficulty had severe arm symptoms. Younger age at surgery (p = .029), mastectomy with reconstruction (p = 0.003), Hispanic ethnicity (p < 0.001), PMRT (p = 0.027), recurrence (p < 0.001), and higher AS score (p < 0.001) were associated with greater financial difficulty. On multivariable analysis, AS score, younger age, Hispanic ethnicity, and recurrence remained associated with financial difficulty. In this study, younger age, Hispanic ethnicity, and arm morbidity were associated with increased risk for financial difficulty. Clarifying how treatment-related adverse events such as arm morbidity increase financial hardship may guide interventions to mitigate this burden.

Shoulder proprioception changesin postmastectomy patients: an observational study.

Breast cancer surgery can cause changes in the anatomical structure of the shoulder and in shoulder mobility, leading to the increased possibility of long-term arm morbidity such as lymphedema. This study aims to evaluate the active shoulder joint position sense (AJPS) with and without lymphedema in postmastectomy patients. A total of 66 women, including 22 patients with lymphedema, 22 patients without lymphedema, and 22 healthy controls, were enrolled in the study. Pain severity was evaluated with the Numeric Pain Scale and edema severity was measured with circumferentially at 10cm intervals. The normal range of motion of the shoulder joint was evaluated with the universal goniometer and the AJPS was assessed by active position repetition testing at 55°, 90°, and 125° shoulder flexion targets using the smartphone application "Clinometer." AJPS at 55°, 90°, and 125° shoulder flexion target angles with and without lymphedema were different in all target angles compared to healthy controls (p < 0.01). There was a difference between the absolute error value of AJPS at 55° flexion (p < 0.05), and no difference at 90° and 125° flexion between the with and without lymphedema groups (p > 0.05). This study shows that the AJPS was negatively affected in with and without lymphedema postmastectomy patients compared to healthy controls. This result emphasizes the importance of adding personalized methods for the restoration of joint position sense in addition to rehabilitation programs generally applied to the patient group.

Abstract PO1-19-03: The T-REX trial: a randomized international non-inferiority trial on Tailored Regional EXternal beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases

Abstract Background: Modern systemic treatment has reduced the incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still indicated in patients with sentinel lymph node (SLN) macrometastases. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease, and secondary cancer. Therefore, there is a need to individualize the indication for regional RT in relation to risk of recurrence. Trial design: In this multicenter, prospective randomized phase 3 trial, eligible patients have a clinically node-negative, estrogen receptor-positive, HER2-negative BC with 1-2 SLN macrometastases, and have not undergone completion axillary lymph node dissection. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axillary levels I-III and the supraclavicular fossa. Internal mammary nodes are targeted in selected patients. After breast-conserving surgery (BCS), RT to the remaining breast is given in both groups while after mastectomy, chest-wall RT is only given in the standard arm. In the intervention arm, chest wall RT may be indicated in selected cases with extensive multifocality, according to national guidelines. RT quality assurance is an integral part of the trial. In addition, material from the primary tumor, SLN metastases and any recurrences is subjected to gene expression analysis to identify both prognostic markers for locoregional recurrence and predictive markers for the benefit of regional RT. After confirmation of eligibility and written informed consent, patients are randomized 1:1 between the treatment arms. Allocation is stratified by trial site and breast surgery (BCS vs. mastectomy). Participation in T-REX should not affect decisions on systemic adjuvant treatment. Eligibility criteria: Trial inclusion and exclusion criteria are given in Table 1. Specific aims: The main aim of the trial is to investigate if the omission of regional RT is non-inferior to routine regional RT in clinically node-negative BC patients with estrogen receptor-positive, HER2-negative T1-2 tumors with 1-2 SLN macrometastases not receiving axillary lymph node dissection. Secondary aims are to investigate whether refraining from regional RT reduces arm morbidity and late RT side effects, and improves short- and long-term health-related quality of life. In addition, the use of genomic classifiers for the prognostication of locoregional recurrences and the prediction of a benefit from regional RT will be investigated. Statistical methods: Primary outcome is recurrence free survival (RFS) at five years. Non-inferiority will be declared if the outcome in the intervention arm is not more than 4.5 percentage units below the standard arm, corresponding to a hazard ratio of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity, and health-related quality of life. Accrual: The trial will include 1350 patients in Sweden, Norway and Finland from April 2023 to December 2028. First sites have been opened in April 2023. Contact information: Primary Investigator: Sara Alkner, Skåne University Hospital, Lund University, sara.alkner@med.lu.se. Responsible for the biobank: Per Karlsson, Sahlgrenska University Hospital, Gothenburg University, per.karlsson@oncology.gu.se. Inclusion and exclusion criteria Citation Format: Sara Alkner, Jana de Boniface, Dan Lundstedt, Ingvil Mjaaland, Lisa Rydén, Johan vikström, Pär-Ola Bendahl, Erik Holmberg, Helena Sackey, Elinore Wieslander, Per Karlsson. The T-REX trial: a randomized international non-inferiority trial on Tailored Regional EXternal beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-03.

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-04.

Abstract PO2-07-03: Retrospective Validation Study of an Artificial Neural Network-Based Preoperative Decision-Support Tool for Noninvasive Lymph Node Staging (NILS) in Women with Primary Breast Cancer (ISRCTN14341750)

Abstract Background Surgical sentinel lymph node biopsy (SLNB) is routinely used to reliably stage axillary lymph nodes in early breast cancer (BC). However, SLNB may be associated with postoperative arm morbidities. For most patients with BC undergoing SLNB, the findings are benign, and the procedure is currently questioned. A decision-support tool for the prediction of benign sentinel lymph nodes based on preoperatively available data has been developed using artificial neural network modelling [1,2]. Methods This was a retrospective geographical and temporal validation study of the noninvasive lymph node staging (NILS) model, based on preoperatively available data from 586 women consecutively diagnosed with primary BC at two sites. Ten preoperative clinicopathological characteristics from each patient were entered into the web-based calculator (Table 1), and the probability of benign lymph nodes was predicted. Vascular invasion, the tenth feature of the NILS model, was difficult to determine preoperatively. Therefore, a separate ANN model was developed to impute this feature, using the other nine features of the NILS model as predictors. A user-friendly web implementation of the NILS model was tested in this study. The performance of the NILS model was assessed in terms of discrimination with the area under the receiver operating characteristic curve (AUC). The primary endpoint was axillary nodal status (discrimination, benign [N0] vs. metastatic axillary nodal status [N+]) determined by the NILS model compared to nodal status by definitive pathology. Results The mean age of the women in the cohort was 65 years, and most of them (93%) had luminal cancers (Table 2). Approximately three-fourths of the patients had no metastases in SLNB (N0 74%). The AUC for the predicted probabilities for the whole cohort was 0.6741 (95% confidence interval: 0.6255–0.7227). More than one in four patients (n=151, 26%) were identified as candidates for SLNB omission when applying the predefined cut-off for lymph node negativity from the development cohort (Table 3). Conclusion The performance of the NILS model was satisfactory. In approximately every fourth patient, SLNB could potentially be omitted. Considering the shift from postoperatively to preoperatively available predictors in this validation study, we have demonstrated the robustness of the NILS model. The clinical usability of the web interface will be evaluated before its clinical implementation. Trial registration Registered in the ISRCTN registry with study ID ISRCTN14341750.

Retrospective validation study of an artificial neural network-based preoperative decision-support tool for noninvasive lymph node staging (NILS) in women with primary breast cancer (ISRCTN14341750)

BackgroundSurgical sentinel lymph node biopsy (SLNB) is routinely used to reliably stage axillary lymph nodes in early breast cancer (BC). However, SLNB may be associated with postoperative arm morbidities. For most patients with BC undergoing SLNB, the findings are benign, and the procedure is currently questioned. A decision-support tool for the prediction of benign sentinel lymph nodes based on preoperatively available data has been developed using artificial neural network modelling.MethodsThis was a retrospective geographical and temporal validation study of the noninvasive lymph node staging (NILS) model, based on preoperatively available data from 586 women consecutively diagnosed with primary BC at two sites. Ten preoperative clinicopathological characteristics from each patient were entered into the web-based calculator, and the probability of benign lymph nodes was predicted. The performance of the NILS model was assessed in terms of discrimination with the area under the receiver operating characteristic curve (AUC) and calibration, that is, comparison of the observed and predicted event rates of benign axillary nodal status (N0) using calibration slope and intercept. The primary endpoint was axillary nodal status (discrimination, benign [N0] vs. metastatic axillary nodal status [N+]) determined by the NILS model compared to nodal status by definitive pathology.ResultsThe mean age of the women in the cohort was 65 years, and most of them (93%) had luminal cancers. Approximately three-fourths of the patients had no metastases in SLNB (N0 74% and 73%, respectively). The AUC for the predicted probabilities for the whole cohort was 0.6741 (95% confidence interval: 0.6255–0.7227). More than one in four patients (n = 151, 26%) were identified as candidates for SLNB omission when applying the predefined cut-off for lymph node-negative status from the development cohort. The NILS model showed the best calibration in patients with a predicted high probability of healthy axilla.ConclusionThe performance of the NILS model was satisfactory. In approximately every fourth patient, SLNB could potentially be omitted. Considering the shift from postoperatively to preoperatively available predictors in this validation study, we have demonstrated the robustness of the NILS model. The clinical usability of the web interface will be evaluated before its clinical implementation.Trial registrationRegistered in the ISRCTN registry with study ID ISRCTN14341750.Date of registration 23/11/2018.

Targeted axillary dissection: worldwide variations in clinical practice.

Targeted axillary dissection (TAD) for the axillary staging of clinically node-positive (cN +) breast cancer patients converting to clinically node negative post neoadjuvant chemotherapy (NAC), has gained popularity due to its minimal false negative rate and low arm morbidity. The aim of this study is to shed more light on the variation in the clinical practice globally in terms of indications and perceived limitations of TAD. A panel of expert breast surgeons constructed a structured questionnaire comprising of 18 questions and asked surgeons worldwide for their opinions and routine practice on TAD. The questionnaire was electronically distributed and answers were collected between May 1st and August 1st 2022. Responses included 137 entries from 36 countries. Of them, 73.7% consider TAD for cN + patients planned to receive NAC. Among them, the greatest number of respondents (45%) perform the procedure for tumours up to T3, whereas 27% regardless of T-stage. The majority (42%) perform TAD on patients with 1-3 positive nodes and only 30% consider TAD when matted nodes are present. HER2 positive and Triple Negative subtypes are more likely to undergo TAD than Luminal A and B (86%, 79.1%, 39.5%, and 62.8%, respectively). Maximum acceptable lymph node burden is median 3 nodes for any subtype with a tendency to accept more positive nodes for Triple Negative. This study demonstrates the differences in current practice regarding TAD as well as the fact that the biology of the tumour heavily affects the method of axillary staging.

A Qualitative Study of Rehabilitation Professionals' Practices to Define the Presence of Arm Morbidity After Breast Cancer Surgery

Background: Rehabilitation professionals (RPs) play a major role in identifying, managing, and treating upper-body issues in individuals following breast cancer surgery. Varying definitions of postoperative arm morbidity in the literature have hampered development of standardized surveillance programs for people undergoing breast cancer surgery within clinical care. Our objective was to explore RPs' practices in defining the presence of arm morbidity after breast cancer surgery. Methods: This qualitative study used semistructured focus group interviews with 29 RPs from 5 health authorities in British Columbia, Canada. Transcripts were analyzed using content analysis. Results: Two categories captured RPs' overarching lack of consensus in defining the presence of postoperative arm morbidity: (1) Complex concerns, complex considerations; and (2) Many ways of measuring arm morbidity. Varying perspectives exist as to which upper-body issues and functional criteria constitute arm morbidity, as well as which characteristics to consider in identifying who is at risk of developing arm morbidity. In tandem, there is currently no gold standard outcome measure or standardized assessment to identify arm morbidity. Conclusion: Because of the complex interaction between different breast cancer treatments and various environmental and personal factors, there is currently a lack of consensus among RPs about how to define and assess arm morbidity. Our findings demonstrate the presence of arm morbidity is challenging to characterize, given its multifaceted presentation, inconsistent approaches to risk stratification across clinical settings and geographical regions the RPs worked, and numerous ways of measuring arm morbidity.

Risk factors for long-term arm morbidities following breast cancer treatments: A systematic review.

To examine the risk factors for arm morbidity following breast cancer treatments, taking a broad view of all types of physical morbidity, including prolonged pain, lymphedema, decreased range of motion, and functional limitations. A systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Studies exploring the risk factors for prolonged arm morbidity following breast cancer surgery and treatments were included. The studies were assessed independently according to pre-eligibility criteria, following data extraction and methodological quality assessment. 1,242 articles were identified. After removing duplicates, the full texts of 1,153 articles were examined. Sixty-nine of these articles met the criteria and were included in the review. These 69 articles identified 29 risk factors for arm morbidity following treatments for breast cancer. The risk of bias was evaluated using NIH study quality assessment tools. The studies reviewed were published between 2001 and 2021 and included a total of 22,886 patients who were followed up for between three months and 10 years. The main risk factors for long-term morbidity are removal of lymph nodes from the axilla, body mass index >30, having undergone a mastectomy, the stage of the disease, radiation therapy, chemotherapy, infection and trauma to the affected arm after surgery. An understanding of the risk factors for prolonged arm morbidity after surgery can help doctors and therapists in making personalized decisions about the need and timing of rehabilitation treatments.

Axillary surgery in oncologic breast surgery: a narrative review.

With the improved survival for breast cancer there is now an increased focus on quality of life after treatment. Axillary surgery is known to be associated with significant risk of arm morbidity feared by the patients, and several studies have shown de-escalation is possible in different settings. In this review, an overview will be given on new techniques and procedures for de-escalation of axillary surgery in breast cancer patients and the subsequent implications for adjuvant systemic treatment. This study is a narrative review. PubMed was searched for relevant publications in English published between January 2018-June 2023. Only publications with major impact on clinical practice have been included with main emphasis on meta-analysis. In addition, Clinicaltrial.gov has been searched for on-going studies. New tracer techniques are described as well as the on-going reduction in axillary lymph node dissection (ALND) at primary surgery even in node positive patients, and the axillary staging possibilities after down-staging of the axilla by neoadjuvant treatment. Finally axillary staging at local recurrence and in case of ductal carcinoma in situ is described. ALND is no longer routinely recommended in many node positive patients and further de-escalation is investigated. The lack of knowledge on precise axillary status will require cooperating studies between oncologists and breast surgeons in order to avoid escalation of systemic treatment due to the lack of applicability of trial eligibility criteria. Furthermore, investigations on the use of axillary imaging for staging are needed.

Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases – an open, multicentre, randomised non-inferiority phase 3 trial

IntroductionModern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with...

Effectiveness of Pre-discharge Educational Intervention Session in the Prevention of Arm Lymphedema Among Post-mastectomy Women in a Teaching Hospital in Bangalore, India.

Lymphedema is a severe post-mastectomy complication that still causes much morbidity in breast cancer patients with axillary lymph node dissection.Therefore, after mastectomy, lymphedema prevention is crucial for long-term survival and an increase in quality of life. Thestudy'sprimaryobjectivewastodeterminewhetherpre-dischargeeducationalinterventionsessions forpost-mastectomy women effectively improve the knowledge in preventing arm lymphedema. A quasi-experimental research study, one-group pretest-posttest design, was conducted in a teaching hospital in Bangalore.Thesampleincluded80females who were diagnosed with breastcancer,had recentlyundergone mastectomy,andhad chemoandradiationtherapy plans.Questions were based on the knowledge of lymphedema preventive concepts, including the definition of the lymphatic system and lymphedema, its causes, symptoms, prevention, and management, and were included in a structured self-administered questionnaire.Conveniencesampling was used among women who had undergone mastectomy for breast cancer.The pre-discharge educational interventions session included instructions on a self or simple lymphatic drainage technique demonstration, arm exercises, and an e-brochure on risk reduction strategies and arm lymphedema prevention. The knowledge of pre-discharge educational interventionsessions highlighting risk reduction/prevention strategies among post-mastectomy women was evaluated using the self-structured knowledge questionnaire pretest and posttest data. The entire study population comprised women who had undergone mastectomy.Almost half of the subjects were older than 55 years.Prior to the intervention, the majority of patients (58) had poor knowledge (72%) about preventing lymphedema, whereas nearly all patients (80) had good knowledge (100%) after the intervention sessions.All participants felt comfortable using the treatment plan to avoid arm lymphedema. The knowledge gain was statistically significant at the 0.05 level. It was determined that pre-discharge educational intervention sessions enhanced post-mastectomy women's awareness and risk reduction behaviors toward preventing arm lymphedema and reducing arm morbidity. Therefore, it is suggested that women who have had breast cancer surgery participate in a pre-discharge educational intervention program. This will guarantee that all mastectomy patients have access to educational information/materials and that risk reduction strategies are followed to prevent lymphedema.

Association of psychological distress with arm morbidity symptoms in breast cancer survivors: outcomes from the use of PHQ-9 and GAD-7 questionnaires.

Although higher survival rates of breast cancer are achieved these days, breast cancer survivors are challenged with unwanted side effects from treatment or management that affect physical, functional, and psychological well-being of an individual. This study aimed to assess psychological distress status in Malaysian breast cancer survivors and factors that affected the condition. A cross-sectional study design was conducted on 162 breast cancer survivors from various breast cancer support groups in Malaysia. Psychological distress status was assessed based on depression and anxiety scores by applying the Malay version of Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7). Both instruments were self-administered along with a set of questionnaires comprising demographic, medical history, quality of life, and upper extremity function assessment. Outcomes from the PHQ-9 and GAD-7 were analyzed for severity level of psychological distress, and its association with relevant variables, arm morbidity symptoms, as well as the duration of cancer survivorship. The univariate analysis showed that breast cancer survivors with arm morbidities after breast surgery had a higher score of depression (5.0 vs 4.0, p = 0.011) and anxiety (3.0 vs 1.0, p = 0.026) than those who did not. Besides that, receiving fewer post-rehabilitation treatments (p = 0.049) and having a family history of cancer (p = 0.022) were correlated with higher anxiety level. The level of depression and anxiety was inversely proportionate with quality of life and positively correlated with greater disability of the arm function (p < 0.05). Subsequent analysis showed that arm morbidity symptoms including difficulties in finding a t-shirt that fits and pain in the arm area after breast cancer surgery were positively associated with ahigher level of psychological distress. Our study demonstrated the association between psychological distress with arm morbidities in breast cancer survivors. Given that arm morbidities can affect not only physical, but psychological well-being, continuous or serial assessment on both aspects during cancer treatment may effectively help to address mental health issue experienced by this cancer population.

Abstract OT1-08-01: AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with clinically axillary lymph node involvement metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR23, Lymph-ICF and SOC 13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 2347 patients from 247 study sites and 23 countries were enrolled in the study between June 2020 and June 2022. Among 1804 patients with a defined surgical concept 758 women were scheduled for ALND, 722 for TAD, 232 for SLNB, 16 for TLNB and 19 for other procedures. A target lymph node was marked in 1215 patients, most frequently using clips/coils (982, 82.0%), followed by magnetic seeds (100, 8.4%), carbon ink (99, 8.3%), radar marker (21, 1.8%), radioactive seeds (5, 0.4%), and other techniques (8, 0.7%). Citation Format: Thorsten Kühn. AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-08-01.