12035 Background: The safety of silicone breast implants (SBIs) has been challenged in various large observational studies that suggest an association with autoimmune and rheumatic diseases (ARDs). Additionally, an increasing number of women seem to attribute constitutional, rheumatic, mental and cognitive symptoms to their SBIs. This constellation of symptoms is often referred to as ‘Breast implant illness (BII). To date, BII is a self-identified diagnosis without an evidence-based definition. The risks of ARDs and BII have not been evaluated in breast cancer survivors with implant-based breast reconstructions. Methods: We conducted a retrospective cohort study among patients treated for breast cancer between 2000 and 2015 in six large regional hospitals. Clinical data and diagnoses of ARDs were obtained up to 2023 from prospectively maintained institutional and nationwide registries. Patients who were alive at the time of study were invited to participate in a survey. The occurrence of eighteen symptoms, that have been associated with BII by international experts, was assessed. The SBI-exposed patients were compared with patients who had received other surgical treatment modalities. In the entire cohort (including deceased patients and survey non-responders), Hazard Ratios (HRs) for receiving an ARD diagnosis were estimated through multivariable Cox models. Among responders to the survey, person-centered symptom clusters were determined through a latent class analysis approach. The association between SBI-exposure and the observed symptom clusters was analyzed in multivariable logistic regression models. Results: Of 12,262 women in the entire cohort, 3,082 (25%) had received a SBI-based breast reconstruction. Median follow-up time was 12.0 (IQR, 7.0) years. Compared with non-exposed patients, patients with an implant-based breast reconstruction did not have an increased risk of ARDs in general (HR, 1.06, 95% CI [0.89–1.27]) or any specific ARD-category or specific condition. In total, 6,073 patients (64.5% of all invited patients) completed the questionnaire including 1,818 patients with an SBI. In the survey cohort, the median follow-up time was 13.7 (IQR, 6.8) years. Five distinct BII-related symptom clusters were identified, none of which were significantly associated with SBI-exposure in multivariable logistic regression analyses. Additionally, when comparing exposed to non-exposed women, women with SBIs did not have a significantly increased risk for any of the individual BII-associated symptoms. Conclusions: Our results indicate that breast cancer patients with SBIs do not have an increased risk of ARDs nor do they experience more BII-associated symptoms compared with breast cancer patients without SBIs. This information can aid healthcare professionals in counseling breast cancer patients who are worried about the alleged long-term harms of SBI(s).

BACKGROUND:The aim of this study was to develop and validate a clinical prediction model to predict the occurrence of persistent hypoparathyroidism after total or completion thyroidectomy. METHODS:This multicentre retrospective cohort study included patients who underwent total or completion thyroidectomy between January 2010 and June 2021 in 12 Dutch hospitals. RESULTS:Of the 366 patients included, 44 (12.0%) patients developed persistent hypoparathyroidism in the first year follow-up after surgery. Multivariable logistic regression analysis showed that ΔPTH the day after surgery, corrected calcium the day after surgery, and not identifying at least one parathyroid during surgery were strong predictors for persistent hypoparathyroidism. The discriminative ability of the model was excellent (optimism-corrected C-index: 0.88, 95% CI: 0.84-0.92) with moderately calibrated predictions. CONCLUSIONS:The model proposed in this study could be used to perform an individual assessment of patients at risk for persistent hypoparathyroidism after total thyroidectomy.

BACKGROUND:"Breast implant illness" (BII) is a constellation of non-specific constitutional, rheumatologic, mental, and cognitive symptoms reported increasingly by women carrying silicone breast implants (SBIs). The impact of BII on the well-being of breast cancer patients with SBI-based breast reconstructions is a subject of debate. METHODS:In a multicenter cohort of breast cancer survivors (n = 9590) treated between 2000 and 2015 in 6 major regional hospitals in the Netherlands, we performed a health survey (response rate 64.7%). The presence of 18 BII-associated symptoms was compared between patients with and without SBIs in multivariable logistic regression models. In a latent class analysis (LCA), distinct symptom patterns were identified in the study population. RESULTS:Median follow-up time was 13.7 (IQR, 6.8) years. Of all SBI-exposed patients (n = 1821), 20.7% reported ≥4 BII-associated symptoms vs 21.2% of non-exposed patients (risk ratio 0.98; 95% CI = 0.88 to 1.09). Joint pain, sicca, sleep impairment, morning stiffness, and shoulder pain were reported most frequently. Patients with SBIs did not have a significantly increased risk of any of the individual BII-associated symptoms. The LCA identified 5 distinct symptom clusters. Patients with SBI-exposure had a lower risk of falling in the most severe symptom cluster (odds ratio 0.64; 95% CI = 0.43 to 0.96). The other symptom clusters were not significantly associated with SBI-exposure. CONCLUSIONS:Our results indicate that breast cancer survivors with SBI-based reconstructions do not experience more BII-associated symptoms than breast cancer survivors without SBIs, challenging the notion of BII as a distinct clinical entity based on a generic silicone-induced biomechanical pathophysiological mechanism. TRIAL REGISTRATION:This study was preregistered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

Background: Due to an increasing incidence, improving survival rates and changes in treatment patterns, a comprehensive overview of trends in breast tumor events (BTE) in breast cancer survivors is highly needed. In this study, contemporary trends in the occurrence of locoregional and contralateral BTE in patients with previous non-metastatic invasive breast cancer in the Netherlands were investigated. Methods. In this nationwide population-based study, women ≥18 years diagnosed with primary non-metastatic invasive breast cancer between 2003-2008 and 2012-2016, treated with local surgery in the Netherlands, were selected. Data on patient-, tumor-, and treatment-related characteristics were retrieved from the Netherlands Cancer Registry. Data on BTE of breast cancer patients diagnosed between 2003 and 2008 were collected 5 years after primary diagnosis from all hospitals in the Netherlands in retrospect by checking all patient files. For patients diagnosed between 2012 and 2016, data on locoregional BTE were collected by linking the NCR to the Nationwide Pathology Archive (PALGA). Patients with suspected locoregional recurrence were selected through an algorithm based on diagnostic codes within the database and dates of occurrence. Descriptive statistics and Chi-squared tests were performed to compare both cohorts with regard to patient-, tumor-, and treatment-related characteristics and to identify potential differences over time. Five-year event rates were calculated per type of BTE (ipsilateral, regional, and contralateral), and stratified for age at primary diagnosis (<50, 50-69, or ≥70), primary tumor stage (stage I, II, or III), primary subtype based on hormone receptor status and human epidermal growth factor receptor 2 (HR+/HER2-, HR+/HER2+, HR-/HER2+, or HR-/HER2-), and primary tumor grade (grade I, II or III). An ipsilateral breast event was defined as an event in the same breast as the primary breast cancer, i.e. an in-breast recurrence or a second primary breast cancer. A regional event was defined as a regional lymph node metastasis on the same side as the primary breast cancer, where regional lymph nodes were defined as either axillary, periclavicular, or internal mammary lymph node regions. A contralateral breast event was defined as an event in the contralateral breast as the primary breast cancer, which could be either in situ or invasive breast cancer. Findings. Of the 121,426 included breast cancer patients, at least one type of BTE was observed in 6,256 patients (5.2%), of which 422 patients (6.7%) had multiple events at the same time (occurring within 30 days). Five-year ipsilateral, regional and contralateral breast event rates decreased from 3.3%, 1.8% and 2.7% in 2003 to 2.0%, 1.3% and 2.0% in 2016, respectively. The largest decreases were shown in ipsilateral breast event rates for stage III (4.7% in 2003 to 1.7% in 2016) and grade III (5.5% in 2003 to 2.1% in 2016). Interpretation. Taking the change of way of notification into account, our study indicates a slight decrease in or at least stable event rates of ipsilateral, regional, and contralateral BTE in breast cancer patients with a primary diagnosis between 2003-2008 and 2012-2016 in the Netherlands. As breast cancer treatment has been personalised increasingly over the last decades, with de-escalation of local treatment and more options in systemic treatment, it is reassuring that BTE have not increased. Citation Format: Sabine Siesling, Joyce Meijer, Marissa C. van Maaren, Linda de Munck, Linetta Koppert, Desirée van den Bongard. Locoregional and contralateral breast tumor events within 5 years after diagnosis of primary breast cancer in the Netherlands: a population-based study including 121,426 breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-12-06.

The EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) are commonly used Patient-Reported Outcome Measures (PROMs) for breast cancer. This study assesses and compares the internal responsiveness of the EQ-5D-5L and EORTC QLQ-C30 in Dutch breast cancer patients during the first year post-surgery. Women diagnosed with breast cancer who completed the EQ-5D-5L and EORTC QLQ-C30 pre-operatively (T0), 6 months (T6), and 12 months post-surgery (T12) were included. Mean differences of the EQ-5D-5L and EORTC QLQ-C30 between baseline and 6 months (delta 1) and between baseline and 12 months post-surgery (delta 2) were calculated and compared against the respective minimal clinically important differences (MCIDs) of 0.08 and 5. Internal responsiveness was assessed using effect sizes (ES) and standardized response means (SRM) for both deltas. In total, 333 breast cancer patients were included. Delta 1 and delta 2 for the EQ-5D-5L index and most scales of the EORTC QLQ-C30 were below the MCID. The internal responsiveness for both PROMs was small (ES and SRM < 0.5), with greater internal responsiveness for delta 1 compared to delta 2. The EQ-5D-5L index showed greater internal responsiveness than the EORTC QLQ-C30 Global Quality of Life scale and summary score. These findings are valuable for the interpretation of both PROMs in Dutch breast cancer research and clinical care.

PurposeSexual distress impacts the quality of life (QoL) of breast cancer patients but is often overlooked in standard care pathways. This study evaluated the prevalence and factors of sexual distress among Dutch breast cancer patients, compared them to the general population, and explored how sexual distress is discussed in clinical settings from the perspectives of patients and healthcare professionals (HCPs).MethodsQuestionnaires containing the Female Sexual Distress Scale (FSDS) and demographic variables were distributed to women with breast cancer. The effect of breast cancer on sexual distress was assessed with a Mann-Whitney U test. Multivariable linear regression was used to analyze variables associated with FSDS. The Sexuality Attitudes and Beliefs Survey (SABS) was sent to HCPs.ResultsBreast cancer patients reported significantly higher sexual distress compared to a Dutch non-breast cancer cohort, respectively 16.38 (SD 11.81) and 23.35 (SD 11.39). Factors associated with higher sexual distress were psychological comorbidities, the body image scale, and being diagnosed >10 years ago. Sexual distress was not discussed as often as patients needed. Barriers to addressing sexual distress were time constraints, HCPs’ confidence in their ability to address sexual distress, and uncertainty about who is responsible for initiation.ConclusionsBreast cancer patients showed significantly higher sexual distress compared to the Dutch population. However, it was not frequently addressed in the consultation room. While some barriers have been identified, this study highlights the importance of further exploring obstacles to integrating discussions about sexual distress into routine care to improve QoL of breast cancer patients.

The sustainability of healthcare systems is under pressure. Unlike care for many other chronic diseases, cancer care has yet to empower patients in effectively self-managing both the medical and emotional consequences of their condition, including adapting to changes in lifestyle and work, which is essential to achieve optimal health and recovery. Although proposed as a potential solution for sustainable healthcare and support for optimal health and recovery already decades ago, practical implementation of digital care lags behind.We believe electronic patient reported outcome measures (ePROMs) could play an important role in creating sustainable healthcare, both to guide complex treatment pathways and to empower survivors to self-manage consequences of diagnosis and treatment. That is, ePROMs can be used for screening and monitoring of symptoms, but also for treatment decision-making and to facilitate communication about quality of life. We therefore see opportunities for improvements in quality of care, quality of life, and survival of cancer patients, as well as research opportunities, as ePROMs collection can lead to better understanding of care needs. The ‘10 Actions for Change report’ of the Advanced Breast Cancer Global Alliance stresses a critical need for improvement of care for metastatic breast cancer (MBC) patients. We therefore in this paper focus on MBC care and research.

BACKGROUND:In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted axillary dissection, increases accuracy. Targeted axillary dissection procedures differ in terms of the targeted lymph node excision technique. This systematic review aimed to provide an overview of targeted axillary dissection procedures regarding definitive marker type and timing of placement: before neoadjuvant systemic therapy (1-step procedure) or after neoadjuvant systemic therapy adjacent to a clip placed before the neoadjuvant therapy (2-step procedure). METHODS:PubMed and Embase were searched, to 4 July 2023, for RCTs, cohort studies, and case-control studies with at least 25 patients. Studies of targeted lymph node excision only (without sentinel lymph node biopsy), or where intraoperative localization of the targeted lymph node was not attempted, were excluded. For qualitative synthesis, studies were grouped by definitive marker and timing of placement. The targeted lymph node identification rate was reported. Study quality was assessed using a National Institutes of Health quality assessment tool. RESULTS:Of 277 unique records, 51 studies with a total of 4512 patients were included. Six definitive markers were identified: wire, 125I-labelled seed, 99mTc, (electro)magnetic/radiofrequency markers, black ink, and a clip. Fifteen studies evaluated one-step procedures, with the identification rate of the targeted lymph node at surgery varying from 8 of 13 to 47 of 47. Forty-one studies evaluated two-step procedures, with the identification rate of the clipped targeted lymph node on imaging after neoadjuvant systemic therapy varying from 49 to 100%, and the identification rate of the targeted lymph node at surgery from 17 of 24 to 100%. Most studies (40 of 51) were rated as being of fair quality. CONCLUSION:Various targeted axillary dissection procedures are used in clinical practice. Owing to study heterogeneity, the optimal targeted lymph node excision technique in terms of identification rate and feasibility could not be determined. Two-step procedures are at risk of not identifying the clipped targeted lymph node on imaging after neoadjuvant systemic therapy.

In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs). Four hundred sixty four female patients with breast cancer treated at Erasmus MC, the Netherlands, completed EQ-5D-5L questionnaires from diagnosis throughout their treatment. Average utilities were calculated stratified by age and treatment. These utilities were applied in CEAs analysing 920 breast cancer screening policies differing in eligible ages and screening interval simulated by the MISCAN-Breast microsimulation model, using a willingness-to-pay threshold of €20,000. The CEAs included varying sets on normative, breast cancer treatment and screening and follow-up utilities. Efficiency frontiers were compared to assess the impact of the utility sets. The calculated average patient utilities were reduced at breast cancer diagnosis and 6 months after surgery and increased toward normative utilities 12 months after surgery. When using normative utility values of 1 in CEAs, QALYs were overestimated compared to using average gender and age-specific values. Only small differences in QALYs gained were seen when varying treatment utilities in CEAs. The CEAs varying screening and follow-up utilities showed only small changes in QALYs gained and the efficiency frontier. Throughout all variations in utility sets, the optimal strategy remained robust; biennial for ages 40-76 years and occasionally biennial 40-74 years. In sum, we recommend to use gender and age stratified normative utilities in CEAs, and patient-based breast cancer utilities stratified by age and treatment or disease stage. Furthermore, despite varying utilities, the optimal screening scenario seems very robust.

BACKGROUND:Axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT combined with pathological axillary treatment response has been proposed to guide de-escalation of axillary treatment for clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy. The aim of this study was to assess whether axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype are predictors of axillary pCR. METHODS:This study included clinically node-positive patients treated with neoadjuvant systemic therapy in the prospective Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy ('RISAS') trial (NCT02800317) with baseline [18F]fluorodeoxyglucose PET/CT imaging available. The predictive value of axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype to estimate axillary pCR was evaluated using logistic regression analysis. Discriminative ability is expressed using ORs with 95% confidence intervals. RESULTS:Overall, 185 patients were included, with an axillary pCR rate of 29.7%. The axillary pCR rate for patients with limited versus advanced baseline axillary disease according to [18F]fluorodeoxyglucose PET/CT was 31.9% versus 26.1% respectively. Axillary disease extent was not a significant predictor of axillary pCR (OR 0.75 (95% c.i. 0.38 to 1.46) (P = 0.404)). There were significant differences in axillary pCR rates between breast cancer molecular subtypes. The lowest probability (7%) was found for hormone receptor+/human epidermal growth factor receptor 2- tumours. Using this category as a reference group, significantly increased ORs of 14.82 for hormone receptor+/human epidermal growth factor receptor 2+ tumours, 40 for hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 6.91 for triple-negative tumours were found (P < 0.001). CONCLUSION:Molecular subtype is a significant predictor of axillary pCR after neoadjuvant systemic therapy, whereas axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT is not.

BACKGROUND:Comparison of quality indicators can improve quality of care. However, case-mix adjustment is deemed essential. The aim of this study was to develop and validate case-mix adjustment models and to evaluate the effect of case-mix adjustment for the quality indicators related to complications after breast cancer surgery. METHODS:Multivariable logistic regression with backward selection (P < 0.1) was used to develop case-mix models in patients undergoing breast cancer surgery (all types, breast-conserving surgery, mastectomy with or without immediate reconstruction) in the Netherlands (NABON Breast Cancer Audit). High-impact complications were defined as Clavien Dindo grade ≥3. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), corrected for optimism with bootstrap validation. Observed-to-expected plots were used to visualize the difference between unadjusted and case-mix adjusted hospital performance (hospital shifts). RESULTS:In total 32 084 patients from 72 hospitals treated in 2021-2022 were included. A between-hospital variation in complication rates was observed for all surgeries (interquartile range 2.4-6.0%), breast-conserving surgery (interquartile range 1.4-3.4%), and mastectomy with (interquartile range 9.4-9.1%) and without reconstruction (interquartile range 3.3-9.7%). Of the considered variables, body mass index, smoking, multifocality and neoadjuvant therapy were weakly associated with complications. However, surgery type was strongly related to complications (AUC 0.70), resulting in noticeable hospital shifts in the quality indicator scores comprising all surgeries. After stratification for surgery type, no evident hospital shifts were observed after case-mix correction. CONCLUSION:For valid comparison of complication rates after breast cancer surgery between hospitals, stratification by surgery type is crucial. Subsequently, the evaluated patient and tumour characteristics have a negligible effect on the hospital variation.

Background: In clinically node-positive (cN+) breast cancer patients treated with neoadjuvant systemic therapy (NST), axillary disease extent on baseline 18F-FDG PET/CT combined with pathologic axillary response to NST has been proposed to guide axillary treatment de-escalation. Nevertheless, axillary pathologic complete response (pCR) was found to strongly depend on breast molecular subtype. This study aimed to assess whether axillary disease extent on baseline 18F-FDG PET/CT and breast molecular subtype are predictors for axillary pCR.

This review aims to investigate the effect of patient-reported symptom monitoring, defined as the process of active and systematic reporting of symptoms initiated by the patient, on the health-related quality of life of breast cancer patients. Evidence suggests that online patient-reported symptom monitoring has the potential to positively impact the health-related quality of life of non-metastatic breast cancer patients, who are receiving systemic therapy. However, there is a lack of literature specifically addressing patient-reported symptom monitoring and HRQoL in metastatic breast cancer patients. Additional research on symptom monitoring and HRQoL in breast cancer patients at all stages and during all phases in the disease trajectory, including its impact on personalized treatment, is needed before integration into routine care can be considered. Validated questionnaires and current implementation frameworks should be used to accelerate knowledge development about symptom monitoring for patients and their healthcare professionals, ultimately enhancing symptom self-management and the efficiency of breast cancer healthcare in the future.

PURPOSE:This study investigated self-reported clinically relevant cognitive impairment of breast cancer patients in routine clinical care and assessed factors associated with new-onset clinically relevant cognitive impairment. METHODS:Cognitive functioning was assessed before start of any treatment (T0) and at 6 (T6) and 12 (T12) months after diagnosis. Cognitive functioning (CF) was measured on a scale of 0-100 with the EORTC QLQ-C30 questionnaire, and the EORTC pre-defined threshold for clinical importance. Multivariable logistic regression analyses was used to identify factors associated with new-onset clinically relevant cognitive impairment at T6 ((CF > 75 at T0 and CF < 75 at T6 and T12) or (CF > 75 at T0 and T6 and <75 at T12)). RESULTS:Pre-treatment, 21% of patients reported clinically relevant cognitive impairment. At T12, percentage was 32%; 20% of patients reported new-onset clinically relevant cognitive impairment at T6 and/or T12. New-onset clinically relevant cognitive impairment was associated with chemo(immuno)therapy and impairment in role and emotional functioning. Younger patients and patients receiving chemo(immuno)therapy were more likely to report new-onset clinically relevant cognitive impairment post treatment. CONCLUSION:One in five breast cancer patients reported clinically relevant cognitive problems before start of treatment. This percentage further increased within the first year, particularly among patients treated with chemo(immuno)therapy. One in five patients reported new-onset clinically relevant cognitive impairment. Ultimately, these patients may benefit from systematic monitoring and potential referral to interventions.

Background: A large variety of staging and treatment strategies is used in daily practice for clinically node positive (cN+) breast cancer treated with neoadjuvant systemic therapy (NST). A nationwide retrospective registry study was conducted to assess the long-term oncologic safety of these strategies.