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Background: Radiation associated angiosarcoma (RAAS) of the breast is a rare malignancy with poor survival. Optimal treatment strategies remain uncertain due to a lack of data, and vary between surgery alone and a combination of surgery with (neo)adjuvant chemotherapy (NACT) and/or re-irradiation. The aim of this study was to evaluate the potential benefit of taxane based NACT., Methods: In this retrospective single center study, all patients with RAAS of the breast treated between 1994 and 2024 are included. Since 2018, NACT is considered a treatment option for this patient population in our institute. The difference in oncological outcomes of patients with and without NACT were compared., Results: Thirty-five women were included. Thirteen (37 %) received NACT of which five (39 %) also had neoadjuvant re-irradiation with hyperthermia. Eleven patients (85 %) received paclitaxel, the other two (15 %) had doxorubicine/docetaxel. Complete pathological response was found in 69 % (n = 9). Median follow up was 41 months (range 24-56) for patients with NACT and 44 (range 20-108) for patients without NACT. In the NACT group, only one patient developed a recurrence after 6.5 years. Patients with NACT had improved oncological outcomes compared to patients without NACT in terms of 3-year local recurrence free survival (100% vs. 63.9 %, p = 0.14), distant metastasis free survival (100 % vs. 47.5 %, p = 0.005), and overall survival (100% vs. 56.1 %, p = 0.016)., Conclusion: In this study, neoadjuvant taxanes for RAAS of the breast leads to improved distant metastasis free survival and overal survival in patients treated with NACT compared to no NACT., Competing Interests: Declaration of competing interest N. Steeghs provided consultation or attended advisory boards for Boehringer Ingelheim, Ellipses Pharma, GlaxoSmithKline, Incyte, Luszana. N Steeghs received research grants from Abbvie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Lixte, Luszana, Merck, Merck Sharp & DohmeMerck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho, Takeda. All outside the submitted work, all payment to the Netherlands Cancer Institute. W. van der Graaf: Advisory boards SpringworkTx, Agenus and PTC Therapeutics (all to the institute) and research grants from Eli Lilly (to the Institute). W. van Houdt: advisory boards of Amgen, Boehringer Ingelheim, Sanofi, Novartis, Sirius Pintuition, Belpharma. All payment to the Netherlands Cancer Institute., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Recently, old concerns linking silicone breast implants (SBIs) with breast cancer have resurfaced. These concerns apply specifically to the risk of breast cancer recurrence in patients who received breast reconstructions with macro-textured SBIs. In this study, the authors investigated the effect of breast reconstruction with macro-textured SBIs on long-term oncologic outcomes of breast cancer patients., Materials and Methods: The authors conducted a retrospective cohort study in two large cancer centres in the Netherlands. Patients who had been treated for primary breast cancer between 1 January 2000 and 31 December 2015 were included. Data on treatment and oncologic outcomes were obtained from prospectively maintained institutional and nationwide registries. Patient files were reviewed manually to complement missing information. Missing data were accounted for by multiple imputations by chained equations (MICE). Reconstruction with a macro-textured SBI was analysed as a time-dependent variable. The main outcomes of interest were locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Hazard ratios (HRs) were estimated using multivariable Cox proportional hazard models., Results: Of the 4695 women who were eligible for inclusion, 2393 had undergone mastectomy. Of these women, 1187 (25%) had received breast reconstruction with a macro-textured SBI. The mean follow-up time was 11.5 (SD, 5.0) years. Compared with women who had undergone a simple mastectomy or autologous breast reconstruction, women with an implant-based reconstruction did not differ significantly in LRRFS or DMFS after accounting for various confounding factors [HR 1.27 (95% CI 0.93-1.72) and HR 0.94 (95% CI 0.74-1.20), respectively]. Sensitivity analysis in complete cases of patients and various subgroup analyses yielded similar results., Conclusion: Reassuringly, in this multi-centre cohort study no difference was found in long-term oncologic outcomes between women who had received breast reconstruction with a macro-textured SBI and women who had undergone a simple mastectomy or autologous breast reconstruction., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aims to evaluate the response to and surgical benefits of neoadjuvant endocrine therapy (NET) in ER+/HER2-breast cancer patients who are clinically high risk, but genomic low risk according to the 70-gene signature (MammaPrint)., Methods: Patients with ER+/HER2-invasive breast cancer with a clinical high risk according to MINDACT, who had a genomic low risk according to the 70-gene signature and were treated with NET between 2015 and 2023 in our center, were retrospectively analyzed. RECIST 1.1 criteria were used to assess radiological response using MRI or ultrasound. Surgical specimens were evaluated to assess pathological response. Two breast cancer surgeons independently scored the eligibility of breast conserving therapy (BCS) pre- and post- NET., Results: Of 72 included patients, 23 were premenopausal (100% started with tamoxifen of which 4 also received OFS) and 49 were postmenopausal (98% started with an aromatase inhibitor). Overall, 8 (11%) showed radiological complete response. Only 1 (1.4%) patient had a pathological complete response (RCB-0) and 68 (94.4%) had a pathological partial response (RCB-1 or RCB-2). Among the 26 patients initially considered for mastectomy, 14 (53.8%) underwent successful BCS. In all 20 clinical node-positive patients, a marked axillary lymph node was removed to assess response. Four out of 20 (20%) patients had a pathological complete response of the axilla., Conclusion: The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:J.P.O., C.F.J., S.A.L.B., C.E.L., J.S., M.T.F.D.V., C.A.D., F.H.D. declare no competing financial or non-financial interests. M.K. reports research funding paid to the institute from BMS, Roche and AstraZeneca and an advisory for AstraZeneca, Daiichi Sankyo, Domain Therapeutics, Alderaan, BMS, MSD and Roche., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Significance: During breast-conserving surgeries, it is essential to evaluate the resection margins (edges of breast specimen) to determine whether the tumor has been removed completely. In current surgical practice, there are no methods available to aid in accurate real-time margin evaluation., Aim: In this study, we investigated the diagnostic accuracy of diffuse reflectance spectroscopy (DRS) combined with tissue classification models in discriminating tumorous tissue from healthy tissue up to 2 mm in depth on the actual resection margin of in vivo breast tissue., Approach: We collected an extensive dataset of DRS measurements on ex vivo breast tissue and in vivo breast tissue, which we used to develop different classification models for tissue classification. Next, these models were used in vivo to evaluate the performance of DRS for tissue discrimination during breast conserving surgery. We investigated which training strategy yielded optimum results for the classification model with the highest performance., Results: We achieved a Matthews correlation coefficient of 0.76, a sensitivity of 96.7% (95% CI 95.6% to 98.2%), a specificity of 90.6% (95% CI 86.3% to 97.9%) and an area under the curve of 0.98 by training the optimum model on a combination of ex vivo and in vivo DRS data., Conclusions: DRS allows real-time margin assessment with a high sensitivity and specificity during breast-conserving surgeries., (© 2024 The Authors.)

The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+) breast cancer patients achieve pathologic complete response (pCR) of the axilla, with higher rates observed in Human Epidermal growth factor Receptor (HER)2-positive or triple negative (TN) breast cancer subtypes. Tailoring axillary treatment for patients with axillary pCR is necessary, as they are unlikely to benefit from axillary lymph node dissection (ALND), but may suffer complications and long-term morbidity such as lymphedema and impaired shoulder motion. By combining pre-PST and post-PST axillary staging techniques, ALND can be omitted in most cN + patients with pCR. Different post-PST staging techniques (MARI/TAD/SN) show low or ultra-low false negative rates for detection of residual disease. More importantly, trials using the MARI (Marking Axillary lymph nodes with Radioactive Iodine seeds) procedure or sentinel lymph node biopsy (SLNB) as axillary staging technique post-PST have already shown the safety of tailoring axillary treatment in patients with an excellent response. Tailored axillary treatment using the MARI procedure in stage I-III breast cancer resulted in 80% reduction of ALND and excellent five-year axillary recurrence free interval (aRFI) of 97%. Similar oncologic outcomes were seen for post-SLNB in stage I-II patients. The MARI technique requires only one invasive procedure pre-NST and a median of one node is removed post-PST, whereas for the SLNB and TAD techniques two to four nodes are removed. A disadvantage of the MARI technique is its use of radioactive iodine, which is subject to extensive regulations., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Breast conserving surgery (BCS) plus radiation treatment is the favored alternative for mastectomy in patients with breast cancer. To allow for breast conservation in patients with large invasive tumors and poor response to neoadjuvant systemic treatment (NST) or patients with extensive ductal carcinoma in situ (DCIS), oncoplastic breast conserving surgery (OPBCS) techniques are introduced. OPBCS allows for breast conservation in a selective group of breast cancer patients who initially would have been treated with mastectomy due to the unfavorable tumor-to-breast ratio. With OPBCS, the oncological tumor excision is combined with plastic surgical breast conservation techniques without compromising oncological safety and maintaining aesthetic outcomes by preserving the shape of the breast. OPBCS should however not be applied to all breast cancer patients and the selection of patients who benefit from OPBCS and the timing of OPBCS are best discussed in a multidisciplinary team (MDT). Caution is required in patients with higher risk of positive margins [e.g., multifocal breast cancer, invasive lobular carcinoma (ILC), larger tumors and DCIS]. In these patients, delayed OPBCS is recommended to facilitate re-excision and maintain excellent breast conserving rates. Despite proven benefits in selected patients, the increase in the adoption of OPBCS is relatively low. This article provides a clinical perspective on OPBCS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-23-40/coif). The authors have no conflicts of interest to declare., (2023 Translational Breast Cancer Research. All rights reserved.)

Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23-1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03-0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30-3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24-87%), 71% (95% CI 48-100%) and 88% (95% CI 74-100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069., (© 2023. Springer Nature Limited.)

During breast-conserving surgeries, it remains challenging to accomplish adequate surgical margins. We investigated different numbers of fibers for fiber-optic diffuse reflectance spectroscopy to differentiate tumorous breast tissue from healthy tissue ex vivo up to 2 mm from the margin. Using a machine-learning classification model, the optimal performance was obtained using at least three emitting fibers (Matthew's correlation coefficient (MCC) of 0.73), which was significantly higher compared to the performance of using a single-emitting fiber (MCC of 0.48). The percentage of correctly classified tumor locations varied from 75% to 100% depending on the tumor percentage, the tumor-margin distance and the number of fibers., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Introduction: Some aspects of the treatment protocol for breast cancer during pregnancy (PrBC) have not been thoroughly studied. This study provides clarity regarding the safety of the use of 125 I-seeds as a localization technique for breast-conserving surgery in patients with PrBC., Methods: To calculate the exposure to the fetus of one 125 I-seed implanted in a breast tumor, we developed a model accounting for the decaying 125 I-source, time to surgery, and the declining distance between the 125 I-seed and the fetus. The primary outcome was the maximum cumulative fetal dose of radiation at consecutive gestational ages (GA)., Results: The cumulative fetal dose remains below 1 mSv if a single 125 I-seed is implanted at a GA of 26 weeks. After a GA of 26 weeks, the fetal dose can be at a maximum of 11.6 mSv. If surgery takes place within two weeks of implantation from a GA of 26 weeks, and one week above a GA of 32 weeks, the dose remains below 1 mSv., Conclusion: The use of 125 I-seeds is safe in PrBC. The maximum fetal exposure remains well below the threshold of 100 mSv, and therefore, does not lead to an increased risk of fetal tissue damage. Still, we propose keeping the fetal dose as low as possible, preferably below 1 mSv.

Introduction: The NABON Breast Cancer Audit showed that more than 70% of the Dutch women undergoing surgery for breast cancer maintained their breast contour by breast-conserving surgery (BCS) or by immediate reconstruction after ablative surgery. The proportion of oncoplastic surgery applied in patients undergoing breast-conserving treatment remains unknown. The aim of our study was to assess the need for standardization of oncoplastic breast-conserving surgery (OPBCS) in an attempt to enable measurement of the quality of OPBCS., Methods: To gain a better understanding of current practice in OPBCS, we sent a questionnaire to all breast surgeons in The Netherlands who are members of the breast surgery working group ( n = 134)., Results: A total of 60 breast surgeons, representing different hospitals in The Netherlands, responded. 61.7% of the breast surgeons performed BCS on 60-100% of their patients. 68.3% responded that BCS was performed using OPS techniques in up to 40% of their patients. OPBCS was defined as level I volume displacement by 45.2% of the breast surgeons and as BCS performed by a breast surgeon and plastic surgeon together by 32.3% of the breast surgeons. 94.5% indicated that there is a need for standardization of the definition of OPBCS in The Netherlands., Conclusion: This study demonstrates that OPBCS is a major part of daily clinical practice of Dutch breast surgeons treating BC patients. Despite this, there is no clear definition of OPS in breast-conserving treatment in The Netherlands. Only after standardization can a classification code and quality indicator be initiated for OPBCS. Ultimately, this will facilitate improvement in quality of BC care., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

There is an unmet clinical need for an accurate, rapid and reliable tool for margin assessment during breast-conserving surgeries. Ultrasound offers the potential for a rapid, reproducible, and non-invasive method to assess margins. However, it is challenged by certain drawbacks, including a low signal-to-noise ratio, artifacts, and the need for experience with the acquirement and interpretation of images. A possible solution might be computer-aided ultrasound evaluation. In this study, we have developed new ensemble approaches for automated breast tumor segmentation. The ensemble approaches to predict positive and close margins (distance from tumor to margin ≤ 2.0 mm) in the ultrasound images were based on 8 pre-trained deep neural networks. The best optimum ensemble approach for segmentation attained a median Dice score of 0.88 on our data set. Furthermore, utilizing the segmentation results we were able to achieve a sensitivity of 96% and a specificity of 76% for predicting a close margin when compared to histology results. The promising results demonstrate the capability of AI-based ultrasound imaging as an intraoperative surgical margin assessment tool during breast-conserving surgery.

Background  Postmastectomy radiotherapy (PMRT) is allegedly associated with a higher risk of complications of combined nipple-sparing or skin-sparing mastectomy and subpectoral direct-to-implant immediate breast reconstruction ([N]SSM/SDTI-IBR). For this reason, this combination is usually advised against or, even, refused in women who need to undergo PMRT. Because this advice has never been justified, we assessed the short-term complications that may potentially be associated with PMRT after [N]SSM/SDTI-IBR. Methods  We compared the complications requiring reintervention and implant loss occurring after 273 [N]SSM/SDTI-IBR that were exposed to PMRT within the first 16 postoperative weeks (interventional group) to those occurring in 739 similarly operated breasts that were not (control group). Additionally, we compared the fraction of complications requiring reintervention occurring after the onset of radiotherapy in the interventional group to that occurring after a comparable postoperative period in the control group. Results  The fraction of breasts requiring unscheduled surgical reinterventions for complications and the loss of implants did not differ significantly between both groups but significantly more reinterventions were needed among the controls ( p  = 0.00). The fraction of events after the onset of radiotherapy in the interventional group was higher than the fraction of events after 6.2 weeks in the control group, but not significantly so. Conclusion  We found no prove for the alleged increase of short-term complications of adjuvant radiotherapy. Therefore, we advise that these should not be considered valid arguments to advice against [N]SSM/SDTI-IBR., Competing Interests: Conflict of Interest None declared., (The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Radiotherapy (RT) is part of the curative treatment of approximately 70% of breast cancer (BC) patients. Wide practice variation has been reported in RT dose, fractionation and its treatment planning for BC. To decrease this practice variation, it is essential to first gain insight into the current variation in RT treatment between institutes. This paper describes the development of the NABON Breast Cancer Audit-Radiotherapy (NBCA-R), a structural nationwide registry of BC RT data of all BC patients treated with at least surgery and RT., Methods: A working group consisting of representatives of the BC Platform of the Dutch Radiotherapy Society selected a set of dose volume parameters deemed to be surrogate outcome parameters, both for tumour control and toxicity. Two pilot studies were carried out in six RT institutes. In the first pilot study, data were manually entered into a secured web-based system. In the second pilot study, an automatic Digital Imaging and Communications in Medicine (DICOM) RT upload module was created and tested., Results: The NBCA-R dataset was created by selecting RT parameters describing given dose, target volumes, coverage and homogeneity, and dose to organs at risk (OAR). Entering the data was made mandatory for all Dutch RT departments. In the first pilot study (N = 1093), quite some variation was already detected. Application of partial breast irradiation varied from 0 to 17% between the 6 institutes and boost to the tumour bed from 26.5 to 70.2%. For patients treated to the left breast or chest wall only, the average mean heart dose (MHD) varied from 0.80 to 1.82 Gy; for patients treated to the breast/chest wall only, the average mean lung dose (MLD) varied from 2.06 to 3.3 Gy. In the second pilot study 6 departments implemented the DICOM-RT upload module in daily practice. Anonymised data will be available for researchers via a FAIR (Findable, Accessible, Interoperable, Reusable) framework., Conclusions: We have developed a set of RT parameters and implemented registration for all Dutch BC patients. With the use of an automated upload module registration burden will be minimized. Based on the data in the NBCA-R analyses of the practice variation will be done, with the ultimate aim to improve quality of BC RT. Trial registration Retrospectively registered., (© 2022. The Author(s).)

Achieving an adequate resection margin during breast-conserving surgery remains challenging due to the lack of intraoperative feedback. Here, we evaluated the use of hyperspectral imaging to discriminate healthy tissue from tumor tissue in lumpectomy specimens. We first used a dataset obtained on tissue slices to develop and evaluate three convolutional neural networks. Second, we fine-tuned the networks with lumpectomy data to predict the tissue percentages of the lumpectomy resection surface. A MCC of 0.92 was achieved on the tissue slices and an RMSE of 9% on the lumpectomy resection surface. This shows the potential of hyperspectral imaging to classify the resection margins of lumpectomy specimens., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Background: There is a trend towards de-escalating axillary staging and treatment in breast cancer patients. On account of neoadjuvant systemic therapy, node-positive breast cancer patients can achieve a pathological complete response of the axilla. It is hypothesized that these patients do not benefit from an axillary lymph node dissection (ALND), and thus may be spared the risk of severe post-surgical morbidity. In an effort to omit standard ALND, less invasive axillary staging procedures are being implemented to establish response-guided treatment. However, it is unclear which less invasive staging procedure is most accurate, and long-term data are missing with regard to their oncologic safety., Summary: This article provides an overview of the literature on currently used less invasive axillary staging procedures, the accuracy and feasibility of these procedures in clinical practice, important issues concerning axillary treatment, and issues to be addressed in ongoing or future studies., Key Messages: More evidence is needed regarding the safety of replacing standard ALND by less invasive axillary staging procedures in terms of long-term prognosis. These less invasive staging procedures not only serve to select patients who may benefit from treatment de-escalation, but also to select patients who may benefit from treatment escalation., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

Purpose: Axillary staging before neoadjuvant systemic therapy in clinically node-positive breast cancer patients with tailored axillary treatment according to the Marking Axillary lymph nodes with radioactive iodine seeds (MARI)-protocol, a protocol developed at the Netherlands Cancer Institute, is performed with [ 18 F] fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). We aimed to assess the value of FDG-PET/CT in prone compared to standard supine position for axillary staging., Methods: We selected patients with FDG-PET/CT in supine and prone position who underwent the MARI-protocol. One hour after administration of 3.5 MBq/kg, [ 18 F]FDG-PET was performed with a low-dose prone position CT-thorax followed by a supine whole-body scan. Scans were separately reviewed by two nuclear medicine physicians and categorized by number of FDG-positive axillary lymph nodes (ALNs; cALN<4 or cALN≥4). Main outcome was axillary up- or downstaging., Results: Of 153 patients included, 24 (16%) patients were up- or downstaged at evaluation of prone images: One observer upstaged 14 patients, downstaged 3  patients and reported a higher number of ALNs (3.6 vs. 3.2, p < 0.001), while staging (4 up- and 5 downstaged) and number of ALNs (2.8 vs. 2.8) did not differ for the other. Observers agreed on up- or downstaging in only 1 (1%) patient. Irrespective of supine or prone position scanning, observers agreed on axillary staging in 124 (81%) patients and disagreed in 5 (3%). Interobserver agreement was lower with prone assessments (86%, K = 0.67) than supine (92%, K = 0.80)., Conclusions: Axillary staging with FDG-PET/CT in prone compared to supine position did not result in concordant up- or downstaging. Therefore, FDG-PET/CT in supine position only can be considered sufficient for axillary staging., (© 2021. The Author(s).)

Background: The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of breast cancer., Methods: Women included in the Netherlands Cancer Registry and diagnosed during four periods in weeks 2-17 of 2020 were compared with reference data from 2018/2019 (averaged). Weekly incidence was calculated by age group and tumor stage. The number of women receiving initial treatment within 3 months of diagnosis was calculated by period, initial treatment, age, and stage. Initial treatment, stratified by tumor behavior (ductal carcinoma in situ [DCIS] or invasive), was analyzed by logistic regression and adjusted for age, socioeconomic status, stage, subtype, and region. Factors influencing time to treatment were analyzed by Cox regression., Results: Incidence declined across all age groups and tumor stages (except stage IV) from 2018/2019 to 2020, particularly for DCIS and stage I disease (p < 0.05). DCIS was less likely to be treated within 3 months (odds ratio [OR] wks2-8 : 2.04, OR wks9-11 : 2.18). Invasive tumors were less likely to be treated initially by mastectomy with immediate reconstruction (OR wks12-13 : 0.52) or by breast conserving surgery (OR wks14-17 : 0.75). Chemotherapy was less likely for tumors diagnosed in the beginning of the study period (OR wks9-11 : 0.59, OR wks12-13 : 0.66), but more likely for those diagnosed at the end (OR wks14-17 : 1.31). Primary hormonal treatment was more common (OR wks2-8 : 1.23, OR wks9-11 : 1.92, OR wks12-13 : 3.01). Only women diagnosed in weeks 2-8 of 2020 experienced treatment delays., Conclusion: The incidence of breast cancer fell in early 2020, and treatment approaches adapted rapidly. Clarification is needed on how this has affected stage migration and outcomes.

Objectives: To improve quality in breast cancer care, large numbers of quality indicators are collected per hospital, but benchmarking remains complex. We aimed to assess the validity of indicators, develop a textbook outcome summary measure, and compare case-mix adjusted hospital performance., Methods: From a nationwide population-based registry, all 79 690 nonmetastatic breast cancer patients surgically treated between 2011 and 2016 in 91 hospitals in The Netherlands were included. Twenty-one indicators were calculated and their construct validity tested by Spearman's rho. Between-hospital variation was expressed by interquartile range (IQR), and all valid indicators were included in the summary measure. Standardized scores (observed/expected based on case mix) were calculated as above (>100) or below (<100) expected. The textbook outcome was presented as a continuous and all-or-none score., Results: The size of between-hospital variation varied between indicators. Sixteen (76%) of 21 quality indicators showed construct validity, and 13 were included in the summary measure after excluding redundant indicators that showed collinearity with others owing to strong construct validity. The median all-or-none textbook outcome score was 49% (IQR 42%-54%) before and 49% (IQR 48%-51%) after case-mix adjustment. From the total of 91 hospitals, 3 hospitals were positive (3%) and 9 (10%) were negative outliers., Conclusions: The textbook outcome summary measure showed discriminative ability when hospital performance was presented as an all-or-none score. Although indicator scores and outlier hospitals should always be interpreted cautiously, the summary measure presented here has the potential to improve Dutch breast cancer quality indicator efforts and could be implemented to further test its validity, feasibility, and usefulness., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Hospital comparisons to improve quality of care require valid and reliable quality indicators. We aimed to test the validity and reliability of 6 breast cancer indicators by quantifying the influence of case-mix and random variation., Methods: The nationwide population-based database included 79 690 patients with breast cancer from 91 Dutch hospitals between 2011 and 2016. The indicator-scores calculated were: (1) irradical breast-conserving surgery (BCS) for invasive disease, (2) irradical BCS for ductal carcinoma-in-situ, (3) breast contour-preserving treatment, (4) magnetic resonance imaging (MRI) before neo-adjuvant chemotherapy, (5) radiotherapy for locally advanced disease, and (6) surgery within 5 weeks from diagnosis. Case-mix and random variation adjustments were performed by multivariable fixed and random effect logistic regression models. Rankability quantified the between-hospital variation, representing unexplained differences that might be the result of the level of quality of care, as low (<50%), moderate (50%-75%), or high (>75%)., Results: All of the indicators showed between-hospital variation with wide (interquartile) ranges. Case-mix adjustment reduced variation in indicators 1 and 3 to 5. Random variation adjustment (further) reduced the variation for all indicators. Case-mix and random variation adjustments influenced the indicator-scores of individual hospitals and their ranking. Rankability was poor for indicator 1, 2, and 5, and moderate for 3, 4, and 6., Conclusions: The 6 indicators lacked validity and/or reliability to a certain extent. Although measuring quality indicators may stimulate quality improvement in general, comparisons and judgments of individual hospital performance should be made with caution if based on indicators that have not been tested or adjusted for validity and reliability, especially in benchmarking., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Selective removal of initially tumor-positive axillary lymph nodes in breast cancer patients who underwent neoadjuvant systemic treatment (NST) improves the accuracy of nodal staging and provides the opportunity for more tailored axillary treatment. This study evaluated whether radioguided occult lesion localization (ROLL) of clip-marked lymph nodes is feasible in clinical practice., Methods: Prior to NST, a clip marker was placed inside a proven tumor-positive lymph node in all breast cancer patients (cTis-4N1-3 M0). After NST, technetium-99m-labeled macroaggregated albumin was injected in the clip-marked lymph nodes. The next day, these ROLL-marked nodes were selectively removed at surgery to evaluate the pathological response of the axilla., Results: Thirty-seven patients (38 axillae) underwent clip insertion. After NST, the clip was visible by ultrasound in 36 procedures (95%). In the other two patients, the ROLL-node injection was performed in a sonographically suspicious unclipped node (1), and near the clip under computed tomography guidance (1). Initial surgery successfully identified the ROLL-marked node with clip in 33 procedures (87%). Removed specimens in the other five procedures contained only the sonographically suspicious tumor-positive unclipped node (1), a node with signs of complete response but no clip (2), a clip without node (1), and tissue without node nor clip, and a second successful ROLL-node procedure was performed (1). Overall, 10 ROLL-marked nodes had no residual disease., Conclusions: This study demonstrates that the ROLL procedure to identify clip-marked lymph nodes is feasible. This facilitates selective removal at surgery and may tailor axillary treatment in patients treated with NST.

Purpose: Complete tumor removal during cancer surgery remains challenging due to the lack of accurate techniques for intraoperative margin assessment. This study evaluates the use of hyperspectral imaging for margin assessment by reporting its use in fresh human breast specimens., Experimental Design: Hyperspectral data were first acquired on tissue slices from 18 patients after gross sectioning of the resected breast specimen. This dataset, which contained over 22,000 spectra, was well correlated with histopathology and was used to develop a support vector machine classification algorithm and test the classification performance. In addition, we evaluated hyperspectral imaging in clinical practice by imaging the resection surface of six lumpectomy specimens. With the developed classification algorithm, we determined if hyperspectral imaging could detect malignancies in the resection surface., Results: The diagnostic performance of hyperspectral imaging on the tissue slices was high; invasive carcinoma, ductal carcinoma in situ , connective tissue, and adipose tissue were correctly classified as tumor or healthy tissue with accuracies of 93%, 84%, 70%, and 99%, respectively. These accuracies increased with the size of the area, consisting of one tissue type. The entire resection surface was imaged within 10 minutes, and data analysis was performed fast, without the need of an experienced operator. On the resection surface, hyperspectral imaging detected 19 of 20 malignancies that, according to the available histopathology information, were located within 2 mm of the resection surface., Conclusions: These findings show the potential of using hyperspectral imaging for margin assessment during breast-conserving surgery to improve surgical outcome., (©2019 American Association for Cancer Research.)

Background: Tumors with homologous recombination deficiency (HRD), such as BRCA1-associated breast cancers, are not able to reliably repair DNA double-strand breaks (DSBs) and are therefore highly sensitive to both DSB-inducing chemotherapy and poly (ADP-ribose) polymerase inhibitors. We have studied markers that may indicate the presence of HRD in HER2-negative breast cancers and related them to neoadjuvant chemotherapy response., Patients and Methods: Array comparative genomic hybridization (aCGH), BRCA1 promoter methylation, BRCA1 messenger RNA (mRNA) expression and EMSY amplification were assessed in 163 HER2-negative pretreatment biopsies from patients scheduled for neoadjuvant chemotherapy., Results: Features of BRCA1 dysfunction were frequent in triple-negative (TN) tumors: a BRCA1-like aCGH pattern, promoter methylation and reduced mRNA expression were observed in, respectively, 57%, 25% and 36% of the TN tumors. In ER+ tumors, a BRCA2-like aCGH pattern and the amplification of the BRCA2 inhibiting gene EMSY were frequently observed (43% and 13%, respectively) and this BRCA2-like profile was associated with a better response to neoadjuvant chemotherapy., Conclusions: Abnormalities associated with BRCA1 inactivation are present in about half of the TN breast cancers but were not predictive of chemotherapy response. In ER+/HER2- tumors, a BRCA2-like aCGH pattern was predictive of chemotherapy response. These findings should be confirmed in independent series., (© The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)