A comparison of treatment allocation and survival between younger and older patients with HER2-overexpressing de novo metastatic breast cancer.

INTRODUCTION: There have been several developments in the treatment of HER2-overexpressing metastatic breast cancer. However, pivotal trials mainly included younger and healthier patients, resulting in a lack of information about the benefits and harms of treatment for most older patients. The aim of this study was to provide an overview of the differences in treatment allocation and survival outcomes over time between younger and older patients with HER2-overexpressing metastatic breast cancer. MATERIALS AND METHODS: All patients from the Netherlands Cancer Registry with de novo metastatic breast cancer between 2005 and 2021 were included. Patients were divided into three age groups: <65, 65-74, and ≥ 75 years. Changes in treatment allocation were graphically depicted over time. Cox proportional hazard models were used to calculate overall survival and Poisson models for relative survival. RESULTS: Overall, 2,722 patients were included. Between 2005 and 2021, the use of targeted therapy as first-line treatment increased for all age groups (<65 years from 33.8% to 90.6%, p < 0.001; 65-74 years from 29.2% to 86.5%, p = 0.001; ≥75 years from 4.3% to 55.8%, p < 0.001). Use of chemotherapy as first-line treatment also increased for all age groups (<65 years from 73.5% to 89.8%, p < 0.001; 65-74 years from 50.0% to 78.4%, p = 0.01; ≥75 years from 8.7% to 37.2%, p = 0.04). Although not statistically significant, the use of endocrine therapy, both as monotherapy and in combination with targeted therapy in the first line, decreased (<65 years 19.1% to 5.5%, p < 0.001; 65-74 years 25.0% to 13.5%, p = 0.03; ≥75 years 65.2% to 37.2%, p = 0.16). Changes in relative and overall survival were similar and improved in all age groups, but most in the youngest age group (relative excess risk [RER] 0.93, 95% confidence interval [CI] 0.91-0.94 per year, p < 0.001), and least in patients ≥75 (RER 0.96, 95% CI 0.93-0.98 per year, p = 0.001). DISCUSSION: The use of first-line chemotherapy and targeted therapy increased in all age groups, while the use of endocrine therapy decreased over time. Nevertheless, the uptake of chemotherapy and targeted therapies was substantially slower in the oldest age group. Overall survival and relative survival improved for all age groups, but these improvements were smaller in the older age groups.

Internal Responsiveness of EQ-5D-5L and EORTC QLQ-C30 in Dutch Breast Cancer Patients during the First Year Post-Surgery: A Longitudinal Cohort Study.

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.

Surgical outcomes and prognosis of HER2+ invasive breast cancer patients with a DCIS component treated with breast-conserving surgery after neoadjuvant systemic therapy.

INTRODUCTION: In up to 72 % of HER2+ invasive breast cancer (IBC), a ductal carcinoma in situ (DCIS) component is present. The presence of DCIS is associated with increased positive surgical margins after breast-conserving surgery (BCS). The aim of this study was to assess surgical margins, recurrence and survival in a nationwide cohort of HER2+ IBC with versus without a DCIS component, treated with neoadjuvant systemic therapy (NST) and BCS. MATERIALS AND METHODS: Women diagnosed with HER2+ IBC treated with NST and BCS, between 2010 and 2019, were selected from the Netherlands Cancer Registry and linked to the Dutch Nationwide Pathology Databank. Kaplan-Meier and Cox regression analyses were performed to determine locoregional recurrence rate (LRR) and overall survival (OS) and associated clinicopathological variables. Surgical outcomes and prognosis were compared between IBC only and IBC+DCIS. RESULTS: A total of 3056 patients were included: 1832 with IBC and 1224 with IBC+DCIS. Patients with IBC+DCIS had significantly more often positive surgical margins compared to IBC (12.8 % versus 4.9 %, p < 0.001). Five-year LRR was significantly higher in patients with IBC+DCIS compared to IBC (6.8 % versus 3.6 %, p < 0.001), but the presence of DCIS itself was not significantly associated with LRR after adjusting for confounders in multivariable analysis. Five-year OS did not differ between IBC+DCIS and IBC (94.9 % versus 95.7 %, p = 0.293). CONCLUSION: The presence of DCIS is associated with higher rates of positive surgical margins, but not with LRR and lower OS when adjusted for confounders. Further research is necessary to adequately select IBC+DCIS patients for BCS after NST.

Tumor-Infiltrating Lymphocytes in Patients With Stage I Triple-Negative Breast Cancer Untreated With Chemotherapy.

Importance: The absolute benefit of chemotherapy for all patients with stage I triple-negative breast cancer (TNBC) is unclear, and biomarkers are not currently available for selecting patients with an excellent outcome for whom neoadjuvant or adjuvant chemotherapy may have negligible benefit. High levels of stromal tumor-infiltrating lymphocytes (sTILs) are associated with favorable survival in TNBC, but data solely in stage I TNBC are lacking. Objective: To examine the outcomes of patients of all ages with stage I TNBC solely and who received neither neoadjuvant nor adjuvant chemotherapy, according to centrally reviewed sTIL levels at prespecified cutoffs. Design, Setting, and Participants: This cohort study used the Netherlands Cancer Registry to identify patients diagnosed with stage I TNBC between January 1, 2005, and December 31, 2015, who were not treated with chemotherapy. Only patients who did not receive neoadjuvant and/or adjuvant chemotherapy were selected. The clinical data were matched with their corresponding pathology data provided by the Dutch Pathology Registry. Data analysis was performed between February and October 2023. Main Outcomes and Measures: The primary end point was breast cancer-specific survival (BCSS) at 5, 10, and 15 years for the prespecified sTIL level cutoffs of 30%, 50%, and 75%. Hematoxylin and eosin-stained slides were used for central review of histologic subtype, grade, and lymphovascular invasion. The International Immuno-Oncology Biomarker Working Group guidelines were used to score the sTIL levels; these levels were determined for 1041 patients. Results: A total of 4511 females with stage I TNBC (mean [SD] age at diagnosis, 64.4 [11.1] years; median follow-up, 11.4 [95% CI, 10.9-11.9] years) were included. Most tumors (952 [91.5%]) were invasive carcinomas of nonspecial histologic subtype. Most patients (548 [52.6%]) had pT1cN0 tumors. Median (range) sTIL level was 5% (1%-99%). A total of 775 patients (74.4%) had sTIL levels below 30%, 266 (25.6%) had 30% or greater, 203 (19.5%) had 50% or greater, and 141 (13.5%) had 75% or greater. Patients with pT1abN0 tumors had a more favorable outcome vs patients with pT1cN0 tumors, with a 10-year BCSS of 92% (95% CI, 89%-94%) vs 86% (95% CI, 82%-89%). In the overall cohort, sTIL levels of at least 30% were associated with better BCSS compared with sTIL levels less than 30% (96% and 87%, respectively; hazard ratio [HR], 0.45; 95% CI, 0.26-0.77). High sTIL levels of 50% or greater were associated with a better outcome than low sTIL levels of less than 50% (HR, 0.27; 95% CI, 0.10-0.74) in patients with pT1C tumors, with a 10-year BCSS of 95% increasing to 98% with sTIL levels of 75% or greater. Conclusions and Relevance: Results of this study showed that patients with stage I TNBC and high level of sTILs who did not receive neoadjuvant or adjuvant chemotherapy had excellent 10-year BCSS. The findings further support the role of sTILs as integral biomarkers in prospective clinical trials of therapy optimization for this patient population.

The effectiveness of personalised surveillance and aftercare in breast cancer follow-up: a systematic review.

PURPOSE: Breast cancer follow-up (surveillance and aftercare) varies from one-size-fits-all to more personalised approaches. A systematic review was performed to get insight in existing evidence on (cost-)effectiveness of personalised follow-up. METHODS: PubMed, Scopus and Cochrane were searched between 01-01-2010 and 10-10-2022 (review registered in PROSPERO:CRD42022375770). The inclusion population comprised nonmetastatic breast cancer patients ≥ 18 years, after completing curative treatment. All intervention-control studies studying personalised surveillance and/or aftercare designed for use during the entire follow-up period were included. All review processes including risk of bias assessment were performed by two reviewers. Characteristics of included studies were described. RESULTS: Overall, 3708 publications were identified, 64 full-text publications were read and 16 were included for data extraction. One study evaluated personalised surveillance. Various personalised aftercare interventions and outcomes were studied. Most common elements included in personalised aftercare plans were treatment summaries (75%), follow-up guidelines (56%), lists of available supportive care resources (38%) and PROs (25%). Control conditions mostly comprised usual care. Four out of seven (57%) studies reported improvements in quality of life following personalisation. Six studies (38%) found no personalisation effect, for multiple outcomes assessed (e.g. distress, satisfaction). One (6.3%) study was judged as low, four (25%) as high risk of bias and 11 (68.8%) as with concerns. CONCLUSION: The included studies varied in interventions, measurement instruments and outcomes, making it impossible to draw conclusions on the effectiveness of personalised follow-up. There is a need for a definition of both personalised surveillance and aftercare, whereafter outcomes can be measured according to uniform standards.

High-value breast cancer care within resource limitations.

Breast cancer care is a costly global health issue where effective management depends on early detection and treatment. A breast cancer diagnosis can result in financial catastrophe especially in low- and middle-income countries (LMIC). Large inequities in breast cancer care are observed and represent a global challenge to caregivers and patients. Strategies to improve early diagnosis include awareness and clinical breast examination in LMIC, and screening in high-income countries (HIC). The use of clinical guidelines for the management of breast cancer is needed. Adapted guidelines from HIC can address disparities in populations with limited resources. Locally developed strategies still provide effective guidance in improving survival. Integrated practice units (IPU) with timely multidisciplinary breast care conferences and patient navigators are required to achieve high-value, personalized breast cancer management in HIC as well as LMIC. Breast cancer patient care should include a quality of life evaluation using ideally patient-reported outcomes (PROM) and experience measurements (PREM). Evaluation of breast cancer outcomes must include the financial cost of delivered care. The resulting value perspective should guide resource allocation and program priorities. The value of care must be improved by translating the findings of social and economic research into practice and resolving systemic inequity in clinical breast cancer research. Cancer survivorship programs must be put in place everywhere. The treatment of patients with metastatic breast cancer must require more attention in the future, especially in LMIC.

Information and communication priorities of patients and healthcare professionals in shared decision making regarding adjuvant systemic breast cancer treatment: A survey study.

PURPOSE: To assess information and communication priorities of patients and healthcare professionals in Shared Decision Making about adjuvant systemic treatment of primary breast cancer and identify key decision-relevant information accordingly. METHODS: Patients (N = 122) and professionals working with breast cancer patients (N = 118), of whom 38 were nurse practitioners and 32 nurses, were recruited using convenience sampling, and surveyed about information/communication aspects key to decision-making, using ranking assignments. We further posed a simple open question, questions about receiving population-based statistics versus personalized statistics concerning treatment outcomes, and their attitude and experience concerning Shared Decision Making. Data were analyzed using descriptive analysis and a qualitative analysis. RESULTS: Both patients and professionals prioritized information about treatment outcomes (i.e., survival, recurrence) as key decision-relevant information for patients. Patients prioritized information about relatively severe treatment side-effects and late effects (e.g., blood clot, stroke), whilst professionals prioritized information about effects that occur relatively often (e.g., hair loss, fatigue). Patients specifically wanted to know if the benefit of treatment is worth the negative impact. Both groups prioritized personalized statistics over population-based statistics. CONCLUSIONS: Some differences between patients and professionals were found in information and communication priorities, specifically related to the different side-effects. It seems worthwhile to precisely address these side-effects in Shared Decision Making concerning adjuvant systemic treatment. Furthermore, it seems important to deliberate together on the question if expected benefit of treatment is worth the potential negative impact for the individual patient.

Evaluation of the Implementation of the Dutch Breast Cancer Surveillance Decision Aid including Personalized Risk Estimates in the SHOUT-BC Study: A Mixed Methods Approach.

BACKGROUND: To improve Shared decision-making (SDM) regarding personalized post-treatment surveillance, the Breast Cancer Surveillance Decision Aid (BCS-PtDA), integrating personalized risk information, was developed and implemented in eight hospitals. The aim of this mixed-methods study was to (1) assess the implementation and participation rates, (2) identify facilitators and barriers for use by health care professionals (HCPs), (3) quantify the observed level of SDM, and (4) evaluate risk communication and SDM application in consultations. METHODS: Implementation and participation rates and patients' BCS-PtDA use were calculated using hospital registry data and BCS-PtDA log data. HCPs' perspective on facilitators and barriers were collected using the MIDI framework. Observed SDM levels in consultation transcripts were quantified using the OPTION-5 scale. Thematic analysis was performed to assess consultation content. RESULTS: The average PtDA implementation and participation rates were, respectively, 26% and 61%. HCPs reported that the PtDA supported choice awareness. Reported barriers for implementation were mainly increased workload and a lack of perceived benefits. The consultation analysis (n = 64) showed patients were offered a choice, but deliberation was lacking. Risk communication was generally adequate. DISCUSSION: When the BCS-PtDA was used, patients were clearly given a choice regarding their post-treatment surveillance, but information provision and SDM application can be improved.

Clinical decision support systems for multidisciplinary team decision-making in patients with solid cancer: Composition of an implementation model based on a scoping review.

Generating guideline-based recommendations during multidisciplinary team (MDT) meetings in solid cancers is getting more complex due to increasing amount of information needed to follow the guidelines. Usage of clinical decision support systems (CDSSs) can simplify and optimize decision-making. However, CDSS implementation is lagging behind. Therefore, we aim to compose a CDSS implementation model. By performing a scoping review of the currently reported CDSSs for MDT decision-making we determined 102 barriers and 86 facilitators for CDSS implementation out of 44 papers describing 20 different CDSSs. The most frequently reported barriers and facilitators for CDSS implementation supporting MDT decision-making concerned CDSS maintenance (e.g. incorporating guideline updates), validity of recommendations and interoperability with electronic health records. Based on the identified barriers and facilitators, we composed a CDSS implementation model describing clinical utility, analytic validity and clinical validity to guide CDSS integration more successfully in the clinical workflow to support MDTs in the future.

Opportunities for personalised follow-up in breast cancer: the gap between daily practice and recurrence risk.

PURPOSE: Follow-up guidelines barely diverge from a one-size-fits-all approach, even though the risk of recurrence differs per patient. However, the personalization of breast cancer care improves outcomes for patients. This study explores the variation in follow-up pathways in the Netherlands using real-world data to determine guideline adherence and the gap between daily practice and risk-based surveillance, to demonstrate the benefits of personalized risk-based surveillance compared with usual care. METHODS: Patients with stage I-III invasive breast cancer who received surgical treatment in a general hospital between 2005 and 2020 were selected from the Netherlands Cancer Registry and included all imaging activities during follow-up from hospital-based electronic health records. Process analysis techniques were used to map patients and activities to investigate the real-world utilisation of resources and identify the opportunities for improvement. The INFLUENCE 2.0 nomogram was used for risk prediction of recurrence. RESULTS: In the period between 2005 and 2020, 3478 patients were included with a mean follow-up of 4.9 years. In the first 12 months following treatment, patients visited the hospital between 1 and 5 times (mean 1.3, IQR 1-1) and received between 1 and 9 imaging activities (mean 1.7, IQR 1-2). Mammogram was the prevailing imaging modality, accounting for 70% of imaging activities. Patients with a low predicted risk of recurrence visited the hospital more often. CONCLUSIONS: Deviations from the guideline were not in line with the risk of recurrence and revealed a large gap, indicating that it is hard for clinicians to accurately estimate this risk and therefore objective risk predictions could bridge this gap.

Impact of the COVID-19 pandemic on the in-hospital diagnostic pathway of breast and colorectal cancer in the Netherlands: A population-based study.

BACKGROUND: In the Netherlands, the COVID-19 pandemic resulted in a temporary halt of population screening for cancer and limited hospital capacity for non-COVID care. We aimed to investigate the impact of the pandemic on the in-hospital diagnostic pathway of breast cancer (BC) and colorectal cancer (CRC). METHODS: 71,159 BC and 48,900 CRC patients were selected from the Netherlands Cancer Registry. Patients, diagnosed between January 2020 and July 2021, were divided into six periods and compared to the average of patients diagnosed in the same periods in 2017-2019. Diagnostic procedures performed were analysed using logistic regression. Lead time of the diagnostic pathway was analysed using Cox regression. Analyses were stratified for cancer type and corrected for age, sex (only CRC), stage and region. RESULTS: For BC, less mammograms were performed during the first recovery period in 2020. More PET-CTs were performed during the first peak, first recovery and third peak period. For CRC, less ultrasounds and more CT scans and MRIs were performed during the first peak. Lead time decreased the most during the first peak by 2 days (BC) and 8 days (CRC). Significantly fewer patients, mainly in lower stages, were diagnosed with BC (-47%) and CRC (-36%) during the first peak. CONCLUSION: Significant impact of the COVID-19 pandemic was found on the diagnostic pathway, mainly during the first peak. In 2021, care returned to the same standards as before the pandemic. Long-term effects on patient outcomes are not known yet and will be the subject of future research.

Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status.

BACKGROUND: Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. METHODS: We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients' outcomes were compared using Cox regression and competing risk models. RESULTS: Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18-3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78-0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9-100%). Conversely, among the 61 patients with gBRCA1m and < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7-65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29-7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19-0.95) incidence of second primary tumors, compared to BRCA1-non-alteration. CONCLUSIONS: Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic: A population-based observational study.

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1-12 2020: pre-COVID-19, weeks 12-20 2020: 1st peak, weeks 21-41 2020: recovery, weeks 42-53 2020: 2nd peak, weeks 1-20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77-0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72-0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p < .001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.

European quality indicators developed by the European Commission Initiative on Breast Cancer: a first nationwide assessment for the Dutch setting.

PURPOSE: This observational study aims to assess the feasibility of calculating indicators developed by the European Commission Initiative on Breast Cancer (ECIBC) for the Dutch breast cancer population. METHODS: Patients diagnosed with invasive or in situ breast cancer between 2012 and 2018 were selected from the Netherlands Cancer Registry (NCR). Outcomes of the quality indicators (QI) were presented as mean scores and were compared to a stated norm. Variation between hospitals was assessed by standard deviations and funnel plots and trends over time were evaluated. The quality indicator calculator (QIC) was validated by comparing these outcomes with the outcomes of constructed algorithms in Stata. RESULTS: In total, 133,527 patients were included. Data for 24 out of 26 QIs were available in the NCR. For 67% and 67% of the QIs, a mean score above the norm and low or medium hospital variation was observed, respectively. The proportion of patients undergoing a breast reconstruction or neoadjuvant systemic therapy increased over time. The proportion treated within 4 weeks from diagnosis, having >10 lymph nodes removed or estrogen negative breast cancer who underwent adjuvant chemotherapy decreased. The outcomes of the constructed algorithms in this study and the QIC showed 100% similarity. CONCLUSION: Data from the NCR could be used for the calculation of more than 92% of the ECIBC indicators. The quality of breast cancer care in the Netherlands is high, as more than half of the QIs already score above the norm and medium hospital variation was observed. The QIC can be easy and reliably applied.

Method of primary breast cancer detection and the disease-free interval, adjusting for lead time.

BACKGROUND: Little is known about the impact of screen-detected breast cancer compared with clinically detected breast cancer on the disease-free interval (ie, free from locoregional recurrences, distant metastasis, contralateral breast cancer). Moreover, it is thought that most studies overestimate the beneficial effect of screening, as they do not adjust for lead time. We investigated the association between method of breast cancer detection and disease-free interval, taking lead time into account. METHODS: Women aged 50-76 years, diagnosed with breast cancer between 2005 and 2008 were selected from the Netherlands Cancer Registry. Women diagnosed in 2005 were divided into screen-detected and clinically detected cancer and had a follow-up of 10 years (2005 cohort). Women diagnosed in 2006-2008 were divided into screen-detected, interval, and nonscreen-related cancer and had a follow-up of 5 years (2006-2008 cohort). A previously published method was used to adjust for lead time. Analyses were repeated correcting for confounding variables instead of lead time. RESULTS: The 2005 cohort included 6215 women. Women with screen-detected cancer had an improved disease-free interval compared with women with clinically detected cancer (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.68 to 0.87). The 2006-2008 cohort included 15 176 women. Women with screen-detected or interval cancer had an improved disease-free interval compared with women with nonscreen-related cancer (HR = 0.76, 95% CI = 0.66 to 0.88; HR = 0.88, 95% CI = 0.78 to 0.99, respectively). Correcting for confounders instead of lead time did not change associations. CONCLUSION: Women with screen-detected cancer had an improved disease-free interval compared with women with a nonscreen-related or clinically detected cancer, after correction for lead time.

Prognostic effect of nodal status before and after neoadjuvant chemotherapy in breast cancer: a Dutch population-based study.

PURPOSE: In breast cancer, neoadjuvant chemotherapy (NAC) can downstage the nodal status, and can even result in a pathological complete response, which is associated with improved prognosis. This study aimed to determine the prognostic effect of nodal status before and after NAC. METHODS: Women with breast cancer treated with NAC were selected from the Netherlands Cancer Registry if diagnosed between 2005 and 2019, and classified based on nodal status before NAC: node-negative (cN0), or node-positive based on fine needle aspiration cytology or core needle biopsy (cN+). Subgroups were based on nodal status after NAC: absence (ypN0) or presence (ypN+) of nodal disease. Five-year overall survival (OS) was assessed with Kaplan-Meier survival analyses, also per breast cancer molecular subtype. To adjust for potential confounders, multivariable analyses were performed. RESULTS: A total of 6,580 patients were included in the cN0 group, and 11,878 in the cN+ group. The 5-year OS of the cN0ypN0-subgroup was statistically significant better than that of the cN+ypN0-subgroup (94.4% versus 90.1%, p < 0.0001). In cN0 as well as cN+ disease, ypN+ had a statistically significant worse 5-year OS compared to ypN0. For hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)-, HR+ HER2+, HR-HER2+, and triple negative disease, respectively, 5-year OS in the cN0ypN+-subgroup was 89.7%, 90.4%, 73.7%, and 53.6%, and in the cN+ypN+-subgroup 84.7%, 83.2%, 61.4%, and 48.8%. In multivariable analyses, cN+ and ypN+ disease were both associated with worse OS. CONCLUSION: This study suggests that both cN-status and ypN-status, and molecular subtype should be considered to further improve prognostication.

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic: A retrospective population-based study.

BACKGROUND: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. AIM: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. DESIGN: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, >1 emergency room contact, >1 hospitalization, hospitalization >14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. PARTICIPANTS: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. RESULTS: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74-0.88 and OR 0.92; 95% CI 0.87-0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. CONCLUSIONS: Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.

Development of machine learning models to predict cancer-related fatigue in Dutch breast cancer survivors up to 15 years after diagnosis.

PURPOSE: To prevent (chronic) cancer-related fatigue (CRF) after breast cancer, it is important to identify survivors at risk on time. In literature, factors related to CRF are identified, but not often linked to individual risks. Therefore, our aim was to predict individual risks for developing CRF. METHODS: Two pre-existing datasets were used. The Nivel-Primary Care Database and the Netherlands Cancer Registry (NCR) formed the Primary Secondary Cancer Care Registry (PSCCR). NCR data with Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship (PROFILES) data resulted in the PSCCR-PROFILES dataset. Predictors were patient, tumor and treatment characteristics, and pre-diagnosis health. Fatigue was GP-reported (PSCCR) or patient-reported (PSCCR-PROFILES). Machine learning models were developed, and performances compared using the C-statistic. RESULTS: In PSCCR, 2224/12813 (17%) experienced fatigue up to 7.6 ± 4.4 years after diagnosis. In PSCCR-PROFILES, 254 (65%) of 390 patients reported fatigue 3.4 ± 1.4 years after diagnosis. For both, models predicted fatigue poorly with best C-statistics of 0.561 ± 0.006 (PSCCR) and 0.669 ± 0.040 (PSCCR-PROFILES). CONCLUSION: Fatigue (GP-reported or patient-reported) could not be predicted accurately using available data of the PSCCR and PSCCR-PROFILES datasets. IMPLICATIONS FOR CANCER SURVIVORS: CRF is a common but underreported problem after breast cancer. We aimed to develop a model that could identify individuals with a high risk of developing CRF, ideally to help them prevent (chronic) CRF. As our models had poor predictive abilities, they cannot be used for this purpose yet. Adding patient-reported data as predictor could lead to improved results. Until then, awareness for CRF stays crucial.

A holistic profile for cancer-related fatigue for women with breast cancer - a qualitative study.

Objective: Cancer- related fatigue (CRF) is one of the most reported long-term effects after breast cancer and severely impacts quality of life. To come towards optimal treatment of multidimensional CRF, the first step is to use a holistic approach to develop a holistic patient profile including the patient's experience and impact of CRF on their life. Methods and measures: Four semi- structured focus groups with twenty- seven breast cancer patients and fourteen interviews with healthcare professionals (HCPs) were held. Reflexive thematic analysis was used to define (sub)themes for the holistic patient profile. The themes of the interviews and focus groups were compared for validity. Results: Breast cancer patients and HCPs described the same five major themes, consisting of experience of CRF, impact and consequences, coping, personality, and CRF treatment. Experience of CRF consists of cognitive, emotional, and physical aspects. Impact and consequences include work, family, partner relation, social contact and hobbies, body, and misunderstanding. Coping consists of twelve (mal)adaptive strategies. Personality and CRF treatment were summarised as themes. Conclusions: A first holistic patient profile was introduced for CRF for breast cancer. This profile can be conceptualized into a questionnaire to collect information for personalized treatment recommendations and monitoring of CRF over time.