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The article presents a study which assessed the reflection and prediction for cerebrospinal spinal fluid (CSF) biomarkers for axonal damage. The study performed baseline magnetic resonance imaging (MRI) to patients with clinically isolated syndrome (CIS). The result of the study shows that there was an increase neurofilament levels in CIS.

Background and Purpose: In the BOOG 2013-08 trial (NCT02271828), cT1-2N0 breast cancer patients were randomized between breast conserving surgery with or without sentinel lymph node biopsy (SLNB) followed by whole breast radiotherapy (WBRT). While awaiting primary endpoint results (axillary recurrence rate), this study aims to perform a quality assurance analysis on protocol adherence and (incidental) axillary radiation therapy (RT) dose., Materials and Methods: Patients were enrolled between 2015 and 2022. Data on prescribed RT and (in 25% of included patients) planning target volumes (PTV) parameters were recorded for axillary levels I-IV and compared between treatment arms. Multivariable linear regression analysis was performed to determine prognostic variables for incidental axillary RT dose., Results: 1,439/1,461 included patients (98.5%) were treated according to protocol and 87 patients (5.9%) received regional RT (SLNB 10.9%, no-SLNB 1.5 %). In 326 patients included in the subgroup analysis, the mean incidental PTV dose at axilla level I was 59.5% of the prescribed breast RT dose. In 5 patients (1.5%) the mean PTV dose at level I was ≥95% of the prescribed breast dose. No statistically or clinically significant differences regarding incidental axillary RT dose were found between treatment arms. Tumour bed boost (yes/no) was associated with a higher incidental mean dose in level I (R 2  = 0.035, F(6, 263) = 1.532, p 0.168)., Conclusion: The results indicate that RT-protocol adherence was high, and that incidental axillary RT dose was low in the BOOG 2013-08 trial. Potential differences between treatmentarms regarding the primary endpoint can thus not be attributed to different axillary radiation doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Omitting sentinel lymph node biopsy (SLNB) in breast cancer treatment results in patients with unknown positive nodal status and potential risk for systemic undertreatment. This study aimed to investigate whether gene expression profiles (GEPs) can lower this risk in cT1-2N0 ER+ HER2- breast cancer patients treated with BCT., Methods: Patients were included if diagnosed between 2011 and 2017 with cT1-2N0 ER+ HER2- breast cancer, treated with BCT and SLNB, and in whom GEP was applied. Adjuvant chemotherapy recommendations based on clinical risk status (Dutch breast cancer guideline of 2020 versus PREDICT v2.1) with and without knowledge on SLNB outcome were compared to GEP outcome. We examined missing adjuvant chemotherapy indications, and the number of GEPs needed to identify one patient at risk for systemic undertreatment., Results: Of 3585 patients, 2863 (79.9%) had pN0 and 722 (20.1%) pN + disease. Chemotherapy was recommended in 1354 (37.8% guideline-2020) and 1888 patients (52.7% PREDICT). Eliminating SLNB outcome (n = 722) resulted in omission of chemotherapy recommendation in 475 (35.1% guideline-2020) and 412 patients (21.8% PREDICT). GEP revealed genomic high risk in 126 (26.5% guideline-2020) and 82 patients (19.9% PREDICT) in case of omitted chemotherapy recommendation in the absence of SLNB. Extrapolated to the whole group, this concerns 3.5% and 2.3%, respectively, resulting in the need for 28-44 GEPs to identify one patient at risk for systemic undertreatment., Conclusion: If no SLNB is performed, clinical risk status according to the guideline of 2020 and PREDICT predicts a very low risk for systemic undertreatment. The number of GEPs needed to identify one patient at risk for undertreatment does not justify its standard use., (© 2023. The Author(s).)

Background: Regional recurrence (RR), also known as lymph node recurrence, is an endpoint in several trials concerning reducing axillary treatment in cT1-2N0 breast cancer patients. The risk of RR may decrease with each subsequent event-free year, affecting the yield and consequently usefulness of long (er) follow-up. The aim of this study is to determine the risk of RR as a first event within five years after diagnosis in subtypes of breast cancer, conditional to being event-free for one, two, three and four years., Methods: From the Netherlands Cancer Registry, cT1-2N0 breast cancer patients diagnosed from 2005 to 2008 were analyzed. Subgroup analysis was performed for pT1-2N+(sn) patients. RR risk was calculated with Kaplan-Meier analysis. Conditional RR (assuming x event-free years) was determined by selecting patients without an event at x years, and calculating the remaining risk for RR within five years after diagnosis., Results: A total of 18,009 cT1-2N0 (all pN stages) breast cancer patients were included. RR occurred in 1.3% of cT1-2N0 and 1.5% of pT1-2N+(sn) patients. The risk of RR varied between subtypes; it was highest for triple negative tumors and lowest for ER + PR + Her2-and ER + Her2+ tumors. After event-free years, the risk of RR decreased subsequently in both groups and in all subtypes. After two event-free years, the risk of RR was 0.8%., Conclusion: The absolute yield of follow-up to detect RR beyond two years is low; for every 125 event-free patients, one RR can be expected until five years. This suggests that follow-up longer than two years is of limited value for detecting RR in both clinical and research setting., Competing Interests: Declaration of competing interest None of the authors reported have a conflict of interest related to the outcomes of this study., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The ACOSOG Z0011 trial showed that completion axillary lymph node dissection (cALND) can be safely omitted for some patients with T1-2 clinically node-negative breast cancer with one to two involved sentinel lymph nodes (SLNs) treated with breast-conserving therapy (BCT). There is little evidence for the safety of omitting cALND for mastectomy-treated patients. Consequently, cALND is often recommended for sentinel node-positive patients treated with mastectomy. The aim of this study is to determine the proportion of patients who could avoid cALND by choosing BCT instead of mastectomy at a tertiary cancer center., Patients and Methods: All T1-2 clinically node-negative breast cancer patients treated with BCT or mastectomy between 2012 and 2017 with metastases in the SLN(s) were selected from a prospectively maintained database. Clinical factors and outcomes were evaluated between the two groups. Differences were compared using Wilcoxon rank-sum test, chi-square test or Fisher's exact test as appropriate. Significance was set at the 0.05 level for all analyses., Results: A total of 306 patients were included, 199 (65.0%) of whom were treated with BCT and 107 (35.0%) with mastectomy. Patients treated with mastectomy were more often treated with cALND compared with those treated with BCT (71.0% versus 26.6%, p < 0.0001). Overall, 52 of the mastectomy patients (68.4%) could have avoided cALND if they had chosen BCT., Conclusions: Patients treated with mastectomy are more likely to receive cALND than those treated with BCT. Axillary management should be addressed during discussion of primary tumor therapy, and cALND may be avoided when patients choose BCT instead of mastectomy.

Background: After breast cancer treatment, follow-up consists of physical examination and mammography for at least 5 years, to detect local and regional recurrence. The risk of recurrence may decrease after event-free time. This study aims to determine the risk of local recurrence (LR) as a first event until 5 years after diagnosis, conditional on being event-free for 1, 2, 3 and 4 years., Methods: From the Netherlands Cancer Registry, all M0 breast cancers diagnosed between 2005 and 2008 were included. LR risk was calculated with Kaplan-Meier analysis, overall and for different subtypes. Conditional LR (assuming x event-free years) was determined by selecting event-free patients at x years, and calculating their LR risk within 5 years after diagnosis., Results: Five-year follow-up was available for 34,453 patients. Overall, five-year LR as a first event occurred in 3.0%. This risk varied for different subtypes and was highest for triple negative (6.8%) and lowest for ER+PR+Her2- (2.2%) tumors. After 1, 2, 3 and 4 event-free years, the average risk of LR before 5 years after diagnosis decreased from 3.0 to 2.4, 1.6, 1.0, and 0.6%. The risk decreased in all subtypes, the effect was most pronounced in subtypes with the highest baseline risk (ER-Her2+ and triple negative breast cancer). After three event-free years, LR risk in the next 2 years was 1% or less in all subtypes except triple negative (1.6%)., Conclusion: The risk of 5-year LR as a first event was low and decreased with the number of event-free years. After three event-free years, the overall risk was 1%. This is reassuring to patients and also suggests that follow-up beyond 3 years may produce low yield of LR, both for individual patients and studies using LR as primary outcome. This can be used as a starting point to tailor follow-up to individual needs.

Introduction: Imaging findings can be affected by histopathological characteristics, such as breast cancer subtypes. The aim was to determine whether the diagnostic performance, in particular negative predictive value (NPV), of axillary US differs per subtype of breast cancer., Methods: All patients diagnosed between 2008 and 2016 in our hospital with primary invasive breast cancer and an axillary US prior to axillary surgery were included. Histopathology of axillary surgery specimens served as gold standard. The NPV, sensitivity, specificity, positive predictive value (PPV) and accuracy of the axillary US were determined for the overall population and for each subtype (ER+/PR+HER2-,HER2+, triple negative tumors). The Chi-square test was used to determine the difference in diagnostic performance parameters between the subtypes., Results: A total of 1094 breast cancer patients were included. Of these, 35 were diagnosed with bilateral breast cancer, resulting in 1129 cancer cases. Most common subtype was ER+/PR+HER2- in 858 cases (76.0%), followed by 150 cases of HER2+ tumors (13.3%) and 121 cases of triple negative tumors (10.7%). Sensitivity, specificity and accuracy of axillary US did not significantly differ between the subtypes. There was a significant difference for NPV between triple negative tumors and HER2+ tumors (90.3% vs. 80.2%, p = 0.05) and between HER2+ and ER/PR+HER2- tumors (80.2% vs. 87.2%, p = 0.04)., Conclusion: There was no significant difference in the diagnostic performance of axillary US between the subtypes, except for NPV. This was highest in triple negative subtype and lowest in HER2+ tumors. This can be explained by the difference in prevalence of axillary lymph node metastases in our cohort., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: This study aims to evaluate whether extracapsular extension (ECE) in the sentinel lymph node (SLN) is associated with involvement of ≥ 4 lymph node metastases at completion axillary lymph node dissection (ALND) and the effect on 5-year disease-free survival (DFS) and 10-year overall survival (OS). ECE in a SLN is usually a contraindication for omitting completion ALND in cT1-2N0 breast cancer patients treated with breast-conserving therapy and 1-2 positive SLN(s)., Methods: All cT1-2N0 breast cancer patients with 1-3 positive SLN(s) who underwent ALND between 2005 and 2008 were selected from the Netherlands Cancer Registry. Logistic regression analysis was used to determine the association between ECE and ≥ 4 lymph node metastases. Five-year DFS and 10-year OS were analyzed using Kaplan-Meier survival analysis. Cox regression analysis was performed to correct for other prognostic factors., Results: A total of 3502 patients were included. Information on ECE was available for 2111 (60.3%) patients, consisting of 741 (35.1%) patients with and 1370 (64.9%) without ECE. The incidence of ≥ 4 lymph node metastases was 116 (15.7%) in the ECE group vs. 80 (5.8%) in the group without ECE (p < 0.001). Five-year DFS rate was 86.4% in the ECE group compared to 88.8% in the group without ECE (p = 0.085). 10-year OS rate was 78.6% compared to 83.0% (p = 0.018), respectively. Cox regression analysis showed that ECE was not an independent prognostic factor for both DFS and OS., Conclusions: ECE was significantly associated with involvement of ≥ 4 lymph node metastases in the completion ALND group. ECE was not an independent prognostic factor for both DFS and OS.

Background: According to the seventh edition of tumour-node-metastasis (TNM) classification, pN3a status in breast cancer patients consists of presence of an infraclavicular lymph node metastasis (LNM) and/or presence of ≥10 axillary LNMs. The aim of this study was to determine whether prognosis of pN3a based on at least an infraclavicular LNM differs from ≥10 axillary LNMs., Methods: Data were obtained from the Netherlands Cancer Registry. All patients were diagnosed between 2005 and 2008 with primary invasive epithelial breast cancer and pN2a or pN3a status as pathologic result. Patients with pN3a were subdivided in pN3a based on at least an infraclavicular LNM or ≥10 axillary LNMs. Disease-free survival (DFS) included any local, regional or contralateral recurrence, distant metastasis or death within 5 years. Kaplan-Meier curves provided information on 5-year DFS and 8-year overall survival (OS). In addition, Cox proportional hazards model was used to measure the effect of relevant clinicopathological variables on DFS and OS., Results: A total of 3400 patients with pN2a and 1788 patients with pN3a were included. In 83 patients, pN3a was based on at least an infraclavicular LNM (4.6%) and in 1705 patients because of ≥10 axillary LNMs (95.4%). After multivariable analyses, DFS and OS were inferior in patients with pN3a based on ≥10 axillary LNMs compared to infraclavicular LNM (DFS 48.8% versus 63.8%, hazard ratio [HR] 1.59, p = 0.036; OS 46.6% versus 63.9%, HR 1.46, p = 0.042). Furthermore, pN2a and pN3a based on infraclavicular LNM had comparable DFS and OS., Conclusion: PN3a status based on an at least an infraclavicular LNM is rare, yet its prognosis is superior to ≥10 axillary LNMs. Reclassification of infraclavicular LNM in the next TNM should therefore be considered into pN2a., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy., Methods: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up., Discussion: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival., Trial Registration: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.