Adherence to the Dutch Breast Cancer Guidelines for Surveillance in Breast Cancer Survivors:Real-World Data from a Pooled Multicenter Analysis

BACKGROUND: Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce. PATIENTS AND METHODS: Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient’s imaging procedures to their demographics, tumor–treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE. RESULTS: The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings. CONCLUSION: Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients’ individual risk profiles for LRR

Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations:First Results from the TESTBREAST Study

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection

A multicenter prospective cohort study to evaluate feasibility of radio-frequency identification surgical guidance for nonpalpable breast lesions: design and rationale of the RFID Localizer 1 Trial

Background: Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions. Methods: This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance. The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events. Discussion: This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery. Trial registration: Netherlands National Trial Register, NL8019, registered on September 12th 2019

Applying Risk-Based Follow-Up Strategies on the Dutch Breast Cancer Population: Consequences for Care and Costs

Objectives: An important aim of follow-up after primary breast cancer treatment is early detection of locoregional recurrences (LRR). This study compares 2 personalized follow-up scheme simulations based on LRR risk predictions provided by a time dependent prognostic model for breast cancer LRR and quantifies their possible follow-up efficiency. Methods: Surgically treated early patients with breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. The INFLUENCE nomogram was used to estimate the 5-year annual LRR. Applying 2 thresholds, they were defined according to Youden's J-statistic and a predefined follow-up sensitivity of 95%, respectively. These patient's risk estimations served as the basis for scheduling follow-up visits; 2 personalized follow-up schemes were simulated. The number of potentially saved follow-up visits and corresponding cost savings for each follow-up scheme were compared with the current Dutch breast cancer guideline recommendation and the observed utilization of follow-up on a training and testing cohort. Results: Using LRR risk-predictions for 30 379 Dutch patients with breast cancer from 2003 to 2006 (training cohort), 2 thresholds were calculated. The threshold according to Youden's approach yielded a follow-up sensitivity of 62.5% and a potential saving of 62.1% of follow-up visits and euro24.8 million in 5 years. When the threshold corresponding to 95% follow-up sensitivity was used, 17% of follow-up visits and euro7 million were saved compared with the guidelines. Similar results were obtained by applying these thresholds to the testing cohort of 11 462 patients from 2007 to 2008. Compared with the observed utilization of follow-up, the potential cost-savings decline moderately. Conclusions: Personalized follow-up schemes based on the INFLUENCE nomogram's individual risk estimations for breast cancer LRR could decrease the number of follow-up visits if one accepts a limited risk of delayed LRR detection

Applying Risk-Based Follow-Up Strategies on the Dutch Breast Cancer Population: Consequences for Care and Costs

Objectives: An important aim of follow-up after primary breast cancer treatment is early detection of locoregional recurrences (LRR). This study compares 2 personalized follow-up scheme simulations based on LRR risk predictions provided by a time dependent prognostic model for breast cancer LRR and quantifies their possible follow-up efficiency. Methods: Surgically treated early patients with breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. The INFLUENCE nomogram was used to estimate the 5-year annual LRR. Applying 2 thresholds, they were defined according to Youden's J-statistic and a predefined follow-up sensitivity of 95%, respectively. These patient's risk estimations served as the basis for scheduling follow-up visits; 2 personalized follow-up schemes were simulated. The number of potentially saved follow-up visits and corresponding cost savings for each follow-up scheme were compared with the current Dutch breast cancer guideline recommendation and the observed utilization of follow-up on a training and testing cohort. Results: Using LRR risk-predictions for 30 379 Dutch patients with breast cancer from 2003 to 2006 (training cohort), 2 thresholds were calculated. The threshold according to Youden's approach yielded a follow-up sensitivity of 62.5% and a potential saving of 62.1% of follow-up visits and euro24.8 million in 5 years. When the threshold corresponding to 95% follow-up sensitivity was used, 17% of follow-up visits and euro7 million were saved compared with the guidelines. Similar results were obtained by applying these thresholds to the testing cohort of 11 462 patients from 2007 to 2008. Compared with the observed utilization of follow-up, the potential cost-savings decline moderately. Conclusions: Personalized follow-up schemes based on the INFLUENCE nomogram's individual risk estimations for breast cancer LRR could decrease the number of follow-up visits if one accepts a limited risk of delayed LRR detection

Breast MRI in patients after breast conserving surgery with sentinel node procedure using a superparamagnetic tracer

Background: A procedure for sentinel lymph node biopsy (SLNB) using superparamagnetic iron-oxide (SPIO) nanoparticles and intraoperative sentinel lymph node (SLN) detection was developed to overcome drawbacks associated with the current standard-of-care SLNB. However, residual SPIO nanoparticles can result in void artefacts at follow-up magnetic resonance imaging (MRI) scans. We present a grading protocol to quantitatively assess the severity of these artefacts and offer an option to minimise the impact of SPIO nanoparticles on diagnostic imaging. Methods: Follow-up mammography and MRI of two patient groups after a magnetic SLNB were included in the study. They received a 2-mL subareolar dose of SPIO (high-dose, HD) or a 0.1-mL intratumoural dose of SPIO (low-dose, LD). Follow-up mammography and MRI after magnetic SLNB were acquired within 4 years after breast conserving surgery (BCS). Two radiologists with over 10-year experience in breast imaging assessed the images and analysed the void artefacts and their impact on diagnostic follow-up. Results: A total of 19 patients were included (HD, n = 13; LD, n = 6). In the HD group, 9/13 patients displayed an artefact on T1-weighted images up to 3.6 years after the procedure, while no impact of the SPIO remnants was observed in the LD group. Conclusions: SLNB using a 2-mL subareolar dose of magnetic tracer in patients undergoing BCS resulted in residual artefacts in the breast in the majority of patients, which may hamper follow-up MRI. This can be avoided by using a 0.1-mL intratumoural dose

The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions

Background: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called “breast implant illness” (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. Methods: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. Discussion: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. Registration: This study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954)