Publications by authors named "Sabine Siesling"

149 Publications

RE: Long-Term Outcomes of Sentinel Lymph Node Biopsy for Ductal Carcinoma in Situ.

JNCI Cancer Spectr 2020 Dec 3;4(6):pkaa079. Epub 2020 Sep 3.

Laboratory of Pathology Dordrecht, Dordrecht, the Netherlands.

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http://dx.doi.org/10.1093/jncics/pkaa079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771425PMC
December 2020

Contralateral breast cancer risk in patients with ductal carcinoma in situ and invasive breast cancer.

NPJ Breast Cancer 2020 Nov 3;6(1):60. Epub 2020 Nov 3.

Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

We aimed to assess contralateral breast cancer (CBC) risk in patients with ductal carcinoma in situ (DCIS) compared with invasive breast cancer (BC). Women diagnosed with DCIS (N = 28,003) or stage I-III BC (N = 275,836) between 1989 and 2017 were identified from the nationwide Netherlands Cancer Registry. Cumulative incidences were estimated, accounting for competing risks, and hazard ratios (HRs) for metachronous invasive CBC. To evaluate effects of adjuvant systemic therapy and screening, separate analyses were performed for stage I BC without adjuvant systemic therapy and by mode of first BC detection. Multivariable models including clinico-pathological and treatment data were created to assess CBC risk prediction performance in DCIS patients. The 10-year cumulative incidence of invasive CBC was 4.8% for DCIS patients (CBC = 1334). Invasive CBC risk was higher in DCIS patients compared with invasive BC overall (HR = 1.10, 95% confidence interval (CI) = 1.04-1.17), and lower compared with stage I BC without adjuvant systemic therapy (HR = 0.87; 95% CI = 0.82-0.92). In patients diagnosed ≥2011, the HR for invasive CBC was 1.38 (95% CI = 1.35-1.68) after screen-detected DCIS compared with screen-detected invasive BC, and was 2.14 (95% CI = 1.46-3.13) when not screen-detected. The C-index was 0.52 (95% CI = 0.50-0.54) for invasive CBC prediction in DCIS patients. In conclusion, CBC risks are low overall. DCIS patients had a slightly higher risk of invasive CBC compared with invasive BC, likely explained by the risk-reducing effect of (neo)adjuvant systemic therapy among BC patients. For support of clinical decision making more information is needed to differentiate CBC risks among DCIS patients.
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http://dx.doi.org/10.1038/s41523-020-00202-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609533PMC
November 2020

Comprehensive trends in incidence, treatment, survival and mortality of first primary invasive breast cancer stratified by age, stage and receptor subtype in the Netherlands between 1989 and 2017.

Int J Cancer 2020 Nov 30. Epub 2020 Nov 30.

Department of Research and Development, Netherlands Comprehensive Cancer Organisation, Utrecht.

Our study aimed to provide a comprehensive overview of trends in incidence, survival, mortality and treatment of first primary invasive breast cancer (BC), according to age, stage and receptor subtype in the Netherlands between 1989 and 2017. Data from all women diagnosed with first primary stage I to IV BC (N = 320 249) were obtained from the Netherlands Cancer Registry. BC mortality and general population data were retrieved from Statistics Netherlands. Age-standardised incidence and mortality rates were calculated with annual percentage change (APC) and average annual percentage change (AAPC) statistics. The relative survival (RS) was used as estimator for disease-specific survival. The BC incidence for all BC patients combined significantly increased until 2013 from 126 to 158 per 100 000 person-years, after which a declining trend was observed. Surgery became less extensive, but (neo-)adjuvant systemic treatments and their combinations were given more frequently. The RS improved for all age groups and for most stages and receptor subtypes, but remained stable for all subtypes since 2012 to 2013 and since 2000 to 2009 for Stage IV BC at 15 years of follow-up. Overall, the 5- and 10-year RS increased from 76.8% (95% confidence interval [CI]: 76.1, 77.4) and 55.9% (95% CI: 54.7, 57.1) in 1989 to 1999 to 91.0% (95% CI: 90.5, 91.5) and 82.9% (95% CI: 82.2, 83.5), respectively, in 2010 to 2016. BC mortality improved regardless of age and overall decreased from 57 to 35 per 100 000 person-years between 1989 and 2017. In conclusion, the BC incidence in the Netherlands has steadily increased since 1989, but the latest trends show promising declines. Survival improved markedly for most patients and the mortality decreased regardless of age.
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http://dx.doi.org/10.1002/ijc.33417DOI Listing
November 2020

Perceived Care and Well-being of Patients With Cancer and Matched Norm Participants in the COVID-19 Crisis: Results of a Survey of Participants in the Dutch PROFILES Registry.

JAMA Oncol 2021 02;7(2):279-284

Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands.

Importance: As the resolution of the coronavirus disease 2019 (COVID-19) crisis is unforeseeable, and/or a second wave of infections may arrive in the fall of 2020, it is important to evaluate patients' perspectives to learn from this.

Objective: To assess how Dutch patients with cancer perceive cancer treatment and follow-up care (including experiences with telephone and video consultations [TC/VC]) and patients' well-being in comparison with a norm population during the COVID-19 crisis.

Design, Setting, And Participants: Cross-sectional study of patients participating in the Dutch Patient Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship (PROFILES) registry and a norm population who completed a questionnaire from April to May 2020.

Main Outcomes And Measures: Logistic regression analysis assessed factors associated with changes in cancer care (treatment or follow-up appointment postponed/canceled or changed to TC/VC). Differences in quality of life, anxiety/depression, and loneliness between patients and age-matched and sex-matched norm participants were evaluated with regression models.

Results: The online questionnaire was completed by 4094 patients (48.6% response), of whom most were male (2493 [60.9%]) and had a mean (SD) age of 63.0 (11.1) years. Of these respondents, 886 (21.7%) patients received treatment; 2725 (55.6%) received follow-up care. Treatment or follow-up appointments were canceled for 390 (10.8%) patients, whereas 160 of 886 (18.1%) in treatment and 234 of 2725 (8.6%) in follow-up had it replaced by a TC/VC. Systemic therapy, active surveillance, or surgery were associated with cancellation of treatment or follow-up appointment. Younger age, female sex, comorbidities, metastasized cancer, being worried about getting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and receiving supportive care were associated with replacement of a consultation with a TC/VC. Patients and norm participants reported that the COVID-19 crisis made them contact their general practitioner (852 of 4068 [20.9%] and 218 of 979 [22.3%]) or medical specialist/nurse (585 of 4068 [14.4%] and 144 of 979 [14.7%]) less quickly when they had physical complaints or concerns. Most patients who had a TC/VC preferred a face-to-face consultation, but 151 of 394 (38.3%) were willing to use a TC/VC again. Patients with cancer were more worried about getting infected with SARS-CoV-2 compared with the 977 norm participants (917 of 4094 [22.4%] vs 175 of 977 [17.9%]). Quality of life, anxiety, and depression were comparable, but norm participants more often reported loneliness (114 of 977 [11.7%] vs 287 of 4094 [7.0%]) than patients with cancer (P = .009).

Conclusions And Relevance: Among patients with cancer in the Netherlands, 1 in 3 reported changes in cancer care in the first weeks of the COVID-19 crisis. Long-term outcomes need to be monitored. The crisis may affect the mental well-being of the general population relatively more than that of patients with cancer.
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http://dx.doi.org/10.1001/jamaoncol.2020.6093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689559PMC
February 2021

The impact of the temporary suspension of national cancer screening programmes due to the COVID-19 epidemic on the diagnosis of breast and colorectal cancer in the Netherlands.

J Hematol Oncol 2020 11 4;13(1):147. Epub 2020 Nov 4.

Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Godebaldkwartier 419, 3511 DT, Utrecht, The Netherlands.

Oncological care was largely derailed due to the reprioritisation of health care services to handle the initial surge of COVID-19 patients adequately. Cancer screening programmes were no exception in this reprioritisation. They were temporarily halted in the Netherlands (1) to alleviate the pressure on health care services overwhelmed by the upsurge of COVID-19 patients, (2) to reallocate staff and personal protective equipment to support critical COVID-19 care, and (3) to mitigate the spread of COVID-19. Utilising data from the Netherlands Cancer Registry on provisional cancer diagnoses between 6 January 2020 and 4 October 2020, we assessed the impact of the temporary halt of national population screening programmes on the diagnosis of breast and colorectal cancer in the Netherlands. A dynamic harmonic regression model with ARIMA error components was applied to assess the observed versus expected number of cancer diagnoses per calendar week. Fewer diagnoses of breast and colorectal cancer were objectified amid the early stages of the initial COVID-19 outbreak in the Netherlands. This effect was most pronounced among the age groups eligible for cancer screening programmes, especially in breast cancer (age group 50-74 years). Encouragingly enough, the observed number of diagnoses ultimately reached and virtually remained at the level of the expected values. This finding, which emerged earlier in age groups not invited for cancer screening programmes, comes on account of the decreased demand for critical COVID-19 care since early April 2020, which, in turn, paved the way forward to resume screening programmes and a broad range of non-critical health care services, albeit with limited operating and workforce capacity. Collectively, transient changes in health-seeking behaviour, referral practices, and cancer screening programmes amid the early stages of the initial COVID-19 epidemic in the Netherlands conjointly acted as an accelerant for fewer breast and colorectal cancer diagnoses in age groups eligible for cancer screening programmes. Forthcoming research is warranted to assess whether the decreased diagnostic scrutiny of cancer during the COVID-19 pandemic resulted in stage migration and altered clinical management, as well as poorer outcomes.
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http://dx.doi.org/10.1186/s13045-020-00984-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609826PMC
November 2020

Assessment of Studies Evaluating Incremental Costs, Effectiveness, or Cost-Effectiveness of Systemic Therapies in Breast Cancer Based on Claims Data: A Systematic Review.

Value Health 2020 11 10;23(11):1497-1508. Epub 2020 Sep 10.

Erasmus School of Health Policy and Management, Erasmus University, Rotterdam, The Netherlands.

Objectives: Large secondary databases, such as those containing insurance claims data, are increasingly being used to compare the effects and costs of treatments in routine clinical practice. Despite their appeal, however, caution must be exercised when using these data. In this study, we aimed to identify and assess the methodological quality of studies that used claims data to compare the effectiveness, costs, or cost-effectiveness of systemic therapies for breast cancer.

Methods: We searched Embase, the Cochrane Library, Medline, Web of Science, and Google Scholar for English-language publications and assessed the methodological quality using the Good Research for Comparative Effectiveness principles. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018103992.

Results: We identified 1251 articles, of which 106 met the inclusion criteria. Most studies were conducted in the United States (74%) and Taiwan (9%) and were based on claims data sets (35%) or claims data linked to cancer registries (58%). Furthermore, most included large samples (mean 17 130 patients) and elderly patients, and they covered various outcomes (eg, survival, adverse events, resource use, and costs). Key methodological shortcomings were the lack of information on relevant confounders, the risk of immortal time bias, and the lack of information on the validity of outcomes. Only a few studies performed sensitivity analyses.

Conclusions: Many comparative studies of cost, effectiveness, and cost-effectiveness have been published in recent decades based on claims data, and the number of publications has increased over time. Despite the availability of guidelines to improve quality, methodological issues persist and are often inappropriately addressed or reported.
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http://dx.doi.org/10.1016/j.jval.2020.05.008DOI Listing
November 2020

Concurrent versus sequential use of trastuzumab and chemotherapy in early HER2+ breast cancer.

Breast Cancer Res Treat 2021 Feb 28;185(3):817-830. Epub 2020 Oct 28.

Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Purpose: The addition of trastuzumab to adjuvant chemotherapy has improved the outcome of human epidermal growth-factor receptor 2 (HER2)-positive breast cancer. Uncertainty remains about the optimal timing of trastuzumab treatment. Therefore, we compared long-term outcome after concurrent versus sequential treatment, in a population-based setting, using data from the nationwide Netherlands Cancer Registry.

Methods: We identified 1843 women diagnosed in The Netherlands from January 1st 2005 until January 1st 2008 with primary, HER2-positive, TNM breast cancer who received adjuvant chemotherapy and trastuzumab. Kaplan-Meier survival estimates and Cox regression were used to compare recurrence-free survival (RFS) and overall survival (OS) between women who received trastuzumab concurrently with versus sequentially after chemotherapy. Hazard ratios (HR) were adjusted for age, year of diagnosis, grade, pathological T-stage, number of positive lymph nodes, ER-status, PR-status, socio-economic status, radiotherapy, hormonal therapy, ovarian ablation, and type of chemotherapy.

Results: After a median follow-up of 8.2 years, RFS events had occurred in 224 out of 1235 (18.1%) concurrently treated women and 129 out of 608 (21.2%) sequentially treated women (adjusted-HR 0.91; 95% confidence interval (CI) 0.67-1.24; P = 0.580). Deaths occurred in 182/1235 (14.7%) concurrently treated women and 104/608 (17.1%) sequentially treated women (adjusted-HR 0.92; 95% CI 0.65-1.29; P = 0.635).

Conclusions: The results of this population-based study are consistent with earlier randomized trials, demonstrating a non-significant difference in outcome for concurrently treated women compared to those who were treated sequentially, suggesting both options are justified.
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http://dx.doi.org/10.1007/s10549-020-05978-8DOI Listing
February 2021

Effects of oncological care pathways in primary and secondary care on patient, professional and health systems outcomes: a systematic review and meta-analysis.

Syst Rev 2020 10 25;9(1):246. Epub 2020 Oct 25.

School of Nursing, Queen's University, Kingston, Canada.

Background: Pathways are frequently used to improve care for cancer patients. However, there is little evidence about the effects of pathways used in oncological care. Therefore, we performed a systematic review and meta-analysis aiming to identify and synthesize existing literature on the effects of pathways in oncological care.

Methods: All patients diagnosed with cancer in primary and secondary/tertiary care whose treatment can be characterized as the strategy "care pathways" are included in this review. A systematic search in seven databases was conducted to gather evidence. Studies were screened by two independent reviewers. Study outcomes regarding patients, professionals, and system level were extracted from each study.

Results: Out of 13,847 search results, we selected 158 articles eligible for full text assessment. One hundred fifty studies were excluded and the remaining eight studies represented 4786 patients. Most studies were conducted in secondary/tertiary care. Length of stay (LOS) was the most common used indicator, and was reported in five studies. Meta-analysis based on subgroups showed an overall shorter LOS regarding gastric cancer (weighted mean difference (WMD)): - 2.75, CI: - 4.67 to - 0.83) and gynecological cancer (WMD: - 1.58, CI: - 2.10 to - 1.05). Costs were reported in six studies and most studies reported lower costs for pathway groups.

Conclusions: Despite the differences between the included studies, we were able to present an evidence base for cancer care pathways performed in secondary/tertiary care regarding the positive effects of LOS in favor of cancer care pathways.

Systematic Review Registration: PROSPERO CRD42017057592.
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http://dx.doi.org/10.1186/s13643-020-01498-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586678PMC
October 2020

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

Authors:
Iris Kramer Maartje J Hooning Nasim Mavaddat Michael Hauptmann Renske Keeman Ewout W Steyerberg Daniele Giardiello Antonis C Antoniou Paul D P Pharoah Sander Canisius Zumuruda Abu-Ful Irene L Andrulis Hoda Anton-Culver Kristan J Aronson Annelie Augustinsson Heiko Becher Matthias W Beckmann Sabine Behrens Javier Benitez Marina Bermisheva Natalia V Bogdanova Stig E Bojesen Manjeet K Bolla Bernardo Bonanni Hiltrud Brauch Michael Bremer Sara Y Brucker Barbara Burwinkel Jose E Castelao Tsun L Chan Jenny Chang-Claude Stephen J Chanock Georgia Chenevix-Trench Ji-Yeob Choi Christine L Clarke J Margriet Collée Fergus J Couch Angela Cox Simon S Cross Kamila Czene Mary B Daly Peter Devilee Thilo Dörk Isabel Dos-Santos-Silva Alison M Dunning Miriam Dwek Diana M Eccles D Gareth Evans Peter A Fasching Henrik Flyger Manuela Gago-Dominguez Montserrat García-Closas José A García-Sáenz Graham G Giles David E Goldgar Anna González-Neira Christopher A Haiman Niclas Håkansson Ute Hamann Mikael Hartman Bernadette A M Heemskerk-Gerritsen Antoinette Hollestelle John L Hopper Ming-Feng Hou Anthony Howell Hidemi Ito Milena Jakimovska Anna Jakubowska Wolfgang Janni Esther M John Audrey Jung Daehee Kang C Marleen Kets Elza Khusnutdinova Yon-Dschun Ko Vessela N Kristensen Allison W Kurian Ava Kwong Diether Lambrechts Loic Le Marchand Jingmei Li Annika Lindblom Jan Lubiński Arto Mannermaa Mehdi Manoochehri Sara Margolin Keitaro Matsuo Dimitrios Mavroudis Alfons Meindl Roger L Milne Anna Marie Mulligan Taru A Muranen Susan L Neuhausen Heli Nevanlinna William G Newman Andrew F Olshan Janet E Olson Håkan Olsson Tjoung-Won Park-Simon Julian Peto Christos Petridis Dijana Plaseska-Karanfilska Nadege Presneau Katri Pylkäs Paolo Radice Gad Rennert Atocha Romero Rebecca Roylance Emmanouil Saloustros Elinor J Sawyer Rita K Schmutzler Lukas Schwentner Christopher Scott Mee-Hoong See Mitul Shah Chen-Yang Shen Xiao-Ou Shu Sabine Siesling Susan Slager Christof Sohn Melissa C Southey John J Spinelli Jennifer Stone William J Tapper Maria Tengström Soo Hwang Teo Mary Beth Terry Rob A E M Tollenaar Ian Tomlinson Melissa A Troester Celine M Vachon Chantal van Ongeval Elke M van Veen Robert Winqvist Alicja Wolk Wei Zheng Argyrios Ziogas Douglas F Easton Per Hall Marjanka K Schmidt

Am J Hum Genet 2020 11 5;107(5):837-848. Epub 2020 Oct 5.

The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Division of Psychosocial Research and Epidemiology, Amsterdam 1066 CX, the Netherlands. Electronic address:

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS was quantified using Cox regression analyses. We assessed PRS interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10 percentile and 20.5% at the 90 percentile of PRS. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
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http://dx.doi.org/10.1016/j.ajhg.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675034PMC
November 2020

Follow-Up Care for Breast and Colorectal Cancer Across the Globe: Survey Findings From 27 Countries.

JCO Glob Oncol 2020 09;6:1394-1411

National Cancer Institute Bethesda, MD.

Purpose: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.

Methods: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes.

Results: Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care.

Conclusion: This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.
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http://dx.doi.org/10.1200/GO.20.00180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529533PMC
September 2020

From Multiple Quality Indicators of Breast Cancer Care Toward Hospital Variation of a Summary Measure.

Value Health 2020 09 15;23(9):1200-1209. Epub 2020 Aug 15.

Department of Public Health, Erasmus MC, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.jval.2020.05.011DOI Listing
September 2020

Effect of Case-Mix and Random Variation on Breast Cancer Care Quality Indicators and Their Rankability.

Value Health 2020 09 18;23(9):1191-1199. Epub 2020 Aug 18.

Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jval.2019.12.014DOI Listing
September 2020

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

Value Health 2020 09 14;23(9):1149-1156. Epub 2020 Aug 14.

Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, The Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands. Electronic address:

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 €24.8 million in 5 years. When the threshold corresponding to 95% follow-up sensitivity was used, 17% of follow-up visits and €7 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.
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http://dx.doi.org/10.1016/j.jval.2020.05.012DOI Listing
September 2020

Breast Cancer: global quality care optimizing care delivery with existing financial and personnel resources.

ESMO Open 2020 09;4(Suppl 2):e000861

Breast Health Global Initiative (BHGI), Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA.

Our vision about breast cancer quality care within a global health framework was recently published by Oxford University Press. The aim of our work was to reflect on the potential to achieve a world-wide improvement in quality care, assessing value for money. The population-based survival estimates from the CONCORD programme and the Breast Health Global Initiative (BHGI) are valuable tools for this global effort. Because cancer care delivery is becoming unsustainable in many countries assessing healthcare value for the cost is becoming increasingly important. Recommendations are made for better global quality care for patients with breast cancer.
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http://dx.doi.org/10.1136/esmoopen-2020-000861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478129PMC
September 2020

Monitoring and evaluation of breast cancer screening programmes: selecting candidate performance indicators.

BMC Cancer 2020 Aug 24;20(1):795. Epub 2020 Aug 24.

Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Background: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection.

Methods: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries.

Results: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate.

Conclusion: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.
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http://dx.doi.org/10.1186/s12885-020-07289-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444070PMC
August 2020

Spatial location of local recurrences after mastectomy: a systematic review.

Breast Cancer Res Treat 2020 Sep 13;183(2):263-273. Epub 2020 Jul 13.

Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Purpose: We performed a systematic review to document the spatial location of local recurrences (LR) after mastectomy.

Methods: A PubMed search was conducted in August 2019 for the following terms: breast [Title/Abstract] AND cancer [Title/Abstract] AND recurrence [Title/Abstract] AND mastectomy [Title/Abstract]. The search was filtered for English language. Exclusion criteria included studies that did not specify the LR location or studies reporting LR associated with inflammatory breast cancer, or other breast cancers such as phyllodes tumours, lymphoma or associated with sarcoma/angiosarcoma.

Results: A total of 3922 titles were identified, of which 21 publications were eligible for inclusion in the final analysis. A total of 6901 mastectomy patients were included (range 25-1694). The mean LR proportion was 3.5%. Among the total of 351 LR lesions, 81.8% were in the subcutaneous tissue and the skin, while 16% were pectoral muscle recurrences.

Conclusion: Local recurrences are mostly located within the subcutaneous tissue and the skin, assumed to result from unrecognized/subclinical tumour foci left behind after mastectomy, surgical implantation of tumour cells in the wound/scar and/or tumour emboli within the subcutaneous lymphatics. Pectoral muscle recurrences are less frequent and may be attributed to residual disease along the posterior surgical margin and/or lymphatic involvement.
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http://dx.doi.org/10.1007/s10549-020-05774-4DOI Listing
September 2020

Impact of mammographic screening and advanced cancer definition on the percentage of advanced-stage cancers in a steady-state breast screening programme in the Netherlands.

Br J Cancer 2020 Sep 9;123(7):1191-1197. Epub 2020 Jul 9.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: To estimate the percentages of advanced-stage breast cancers (BCs) detected during the course of a steady-state screening programme when using different definitions of advanced BC.

Methods: Data of women aged 49-74 years, diagnosed with BC in 2006-2015, were selected from the Netherlands Cancer Registry and linked to the screening registry. BCs were classified as screen-detected, interval or non-screened. Three definitions of advanced BC were used for comparison: TNM stage (III-IV), NM stage (N+ and/or M+) and T size (invasive tumour ≥15 mm). Analyses were performed assuming a 10% overdiagnosis rate. In sensitivity analyses, this assumption varied from 0 to 30%.

Results: We included 46,734 screen-detected, 17,362 interval and 24,189 non-screened BCs. By TNM stage, 4.9% of screen-detected BCs were advanced, compared with 19.4% and 22.8% of interval and non-screened BCs, respectively (p < 0.001). Applying the other definitions led to higher percentages of advanced BC being detected. Depending on the definition interval, non-screened BCs had a 2-5-times risk of being advanced.

Conclusion: Irrespective of the definition, screen-detected BCs were less frequently in the advanced stage. These findings provide evidence of a stage shift to early detection and support the potential of mammographic screening to reduce treatment-related burdens and the mortality associated with BC.
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http://dx.doi.org/10.1038/s41416-020-0968-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524754PMC
September 2020

Clinical decision trees support systematic evaluation of multidisciplinary team recommendations.

Breast Cancer Res Treat 2020 Sep 6;183(2):355-363. Epub 2020 Jul 6.

Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Purpose: EUSOMA's recommendation that "each patient has to be fully informed about each step in the diagnostic and therapeutic pathway" could be supported by guideline-based clinical decision trees (CDTs). The Dutch breast cancer guideline has been modeled into CDTs ( www.oncoguide.nl ). Prerequisites for adequate CDT usage are availability of necessary patient data at the time of decision-making and to consider all possible treatment alternatives provided in the CDT.

Methods: This retrospective single-center study evaluated 394 randomly selected female patients with non-metastatic breast cancer between 2012 and 2015. Four pivotal CDTs were selected. Two researchers analyzed patient records to determine to which degree patient data required per CDT were available at the time of multidisciplinary team (MDT) meeting and how often multiple alternatives were actually reported.

Results: The four selected CDTs were indication for magnetic resonance imaging (MRI) scan, preoperative and adjuvant systemic treatment, and immediate breast reconstruction. For 70%, 13%, 97% and 13% of patients, respectively, all necessary data were available. The two most frequent underreported data-items were "clinical M-stage" (87%) and "assessable mammography" (28%). Treatment alternatives were reported by MDTs in 32% of patients regarding primary treatment and in 28% regarding breast reconstruction.

Conclusion: Both the availability of data in patient records essential for guideline-based recommendations and the reporting of possible treatment alternatives of the investigated CDTs were low. To meet EUSOMA's requirements, information that is supposed to be implicitly known must be explicated by MDTs. Moreover, MDTs have to adhere to clear definitions of data-items in their reporting.
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http://dx.doi.org/10.1007/s10549-020-05769-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383031PMC
September 2020

Long-Term Health-Related Quality of Life after Four Common Surgical Treatment Options for Breast Cancer and the Effect of Complications: A Retrospective Patient-Reported Survey among 1871 Patients.

Plast Reconstr Surg 2020 07;146(1):1-13

From the Department of Plastic and Reconstructive Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam; Department of Research, Netherlands Comprehensive Cancer Organisation; Department of Health Technology and Services Research, Technical Medical Centre, University of Twente; Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus Medical Center; Department of Plastic, Reconstructive, and Hand Surgery, Hospital Medisch Spectrum Twente/Hospital Group Twente; and Department of Surgery, Hospital Group Twente.

Background: Differences in quality-of-life outcomes after different surgical breast cancer treatment options, including breast reconstruction, are relevant for counseling individual patients in clinical decision-making, and for (societal) evaluations such as cost-effectiveness analyses. However, current literature shows contradictory results, because of use of different patient-reported outcome measures and study designs with limited patient numbers. The authors set out to improve this evidence using patient-reported outcome measures in a large, cross-sectional study for different surgical breast cancer treatment options.

Methods: Quality of life was assessed through the EQ-5D-5L, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23, and the BREAST-Q. Patients with different treatments were compared after propensity-weighted adjustment of pretreatment differences. The EQ-5D was used to value the effect of surgical complications.

Results: A total of 1871 breast cancer patients participated (breast-conserving surgery, n = 615; mastectomy, n = 507; autologous reconstruction, n = 330; and implant-based reconstruction, n = 419). Mastectomy patients reported the lowest EQ-5D score (mastectomy, 0.805, breast-conserving surgery, 0.844; autologous reconstruction, 0.849; and implant-based reconstruction, 0.850) and functioning scores of the C30 questionnaire. On the BREAST-Q, autologous reconstruction patients had higher mean Satisfaction with Outcome, Satisfaction with Breasts, and Sexual Well-being scores than implant-based reconstruction patients. Complications in autologous reconstruction patients resulted in a substantially lower quality of life than in implant-based reconstruction patients.

Conclusions: This study shows the added value of breast conservation and reconstruction compared with mastectomy; however, differences among breast-conserving surgery, implant-based reconstruction, and autologous breast reconstruction were subtle. Complications resulted in poorer health-related quality of life.
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http://dx.doi.org/10.1097/PRS.0000000000006887DOI Listing
July 2020

Adjuvant chemotherapy in small node-negative triple-negative breast cancer.

Eur J Cancer 2020 08 14;135:66-74. Epub 2020 Jun 14.

Department of Medical Oncology, The Netherlands Cancer Institute, PO Box 90203, 1006 BE, Amsterdam, the Netherlands. Electronic address:

Background: Recommendations on adjuvant chemotherapy in pT1N0M0 triple-negative breast cancer (TNBC) differ among international guidelines owing to lack of randomized trial data. We evaluated associations of adjuvant chemotherapy with a long-term outcome in a population-based cohort of pT1N0M0 TNBC.

Methods: All patients diagnosed with pT1N0M0 TNBC in the Netherlands between 2005 and 2016 were identified from the Netherlands Cancer Registry. Patient, tumour and treatment characteristics were recorded. The date and cause of death were obtained from Statistics Netherlands. We used multivariable Cox regression models to evaluate associations of adjuvant chemotherapy with breast cancer-specific survival (BCSS) and overall survival (OS), adjusted for baseline characteristics and performed sensitivity analyses using propensity score (PS) weighting.

Results: We identified 4366 patients: 284 with pT1a, 923 with pT1b and 3159 with pT1c tumours. Adjuvant chemotherapy was administered in 53% of patients. Patients receiving chemotherapy had more unfavourable baseline characteristics including younger age, larger tumours and higher tumour grade. At 8.2 years median follow-up (interquartile range = 5.8-10.9), 671 patients had died, of whom 311 because of breast cancer. After adjustment for baseline characteristics, chemotherapy was associated with improved BCSS (adjusted hazard ratio [aHR] = 0.65; 95% confidence interval [CI] = 0.48-0.89). The effect of chemotherapy differed by tumour size (pT1a: aHR = 4.28, 95% CI = 1.12-16.44; pT1b: aHR = 1.12, 95% CI = 0.51-2.49; pT1c: aHR = 0.60, 95% CI = 0.43-0.82; p = 0.02). Findings for OS were in line with BCSS results. PS-weighting analysis confirmed the results of the primary analysis.

Conclusions: Adjuvant chemotherapy is associated with better BCSS and OS in pT1N0M0 TNBC. Better outcome is most evident in pT1c tumours and may not outweigh harm in pT1a/pT1b tumours.
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http://dx.doi.org/10.1016/j.ejca.2020.04.033DOI Listing
August 2020

Evaluating the Age-Based Recommendations for Long-Term Follow-Up in Breast Cancer.

Oncologist 2020 09 29;25(9):e1330-e1338. Epub 2020 Jun 29.

Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, The Netherlands.

Background: After 5 years of annual follow-up following breast cancer, Dutch guidelines are age based: annual follow-up for women <60 years, 60-75 years biennial, and none for >75 years. We determined how the risk of recurrence corresponds to these consensus-based recommendations and to the risk of primary breast cancer in the general screening population.

Subjects, Materials, And Methods: Women with early-stage breast cancer in 2003/2005 were selected from the Netherlands Cancer Registry (n = 18,568). Cumulative incidence functions were estimated for follow-up years 5-10 for locoregional recurrences (LRRs) and second primary tumors (SPs). Risks were compared with the screening population without history of breast cancer. Alternative cutoffs for age were determined by log-rank tests.

Results: The cumulative risk for LRR/SP was lower in women <60 years (5.9%, 95% confidence interval [CI] 5.3-6.6) who are under annual follow-up than for women 60-75 (6.3%, 95% CI 5.6-7.1) receiving biennial visits. All risks were higher than the 5-year risk of a primary tumor in the screening population (ranging from 1.4% to 1.9%). Age cutoffs <50, 50-69, and > 69 revealed better risk differentiation and would provide more risk-based schedules. Still, other factors, including systemic treatments, had an even greater impact on recurrence risks.

Conclusion: The current consensus-based recommendations use suboptimal age cutoffs. The proposed alternative cutoffs will lead to a more balanced risk-based follow-up and thereby more efficient allocation of resources. However, more factors should be taken into account for truly individualizing follow-up based on risk for recurrence.

Implications For Practice: The current age-based recommendations for breast cancer follow-up after 5 years are suboptimal and do not reflect the actual risk of recurrent disease. This results in situations in which women with higher risks actually receive less follow-up than those with a lower risk of recurrence. Alternative cutoffs could be a start toward risk-based follow-up and thereby more efficient allocation of resources. However, age, or any single risk factor, is not able to capture the risk differences and therefore is not sufficient for determining follow-up. More risk factors should be taken into account for truly individualizing follow-up based on the risk for recurrence.
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http://dx.doi.org/10.1634/theoncologist.2019-0973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485372PMC
September 2020

Patients' perceptions of 70-gene signature testing: commonly changing the initial inclination to undergo or forego chemotherapy and reducing decisional conflict.

Breast Cancer Res Treat 2020 Jul 19;182(1):107-115. Epub 2020 May 19.

Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands.

Purpose: Little is known about the impact of 70-gene signature (70-GS) use on patients' chemotherapy decision-making. The primary aim of this study was to evaluate the impact of 70-GS use on patients' decisions to undergo chemotherapy. The perceived decision conflict during decision-making was a secondary objective of the study.

Methods: Patients operated for estrogen receptor positive early breast cancer were asked to fill out a questionnaire probing their inclination to undergo chemotherapy before deployment of the 70-GS test. After disclosure of the 70-GS result patients were asked about their decision regarding chemotherapy. Patients' decisional conflict was measured using the 16-item decisional conflict scale (DCS); scores < 25 are associated with a persuaded decision while a score > 37.5 implies that one feels unsure about a choice.

Results: Between January 1th 2017 and December 31th 2018, 106 patients completed both questionnaires. Before deployment of the 70-GS, 58% of patients (n = 62) formulated a clear treatment preference, of whom 21 patients (34%) changed their opinion on treatment with chemotherapy following the 70-GS. The final decision regarding chemotherapy was in line with the 70-GS result in 90% of patients. The percentage of patients who felt unsure about their preference to be treated with chemotherapy decreased from 42 to 5% after disclosure of the 70-GS. The mean total DCS significantly decreased from pre-test to post-test from 35 to 23, irrespective of the risk estimate (p < 0.001).

Conclusion: Deployment of the 70-GS changed patients' inclination to undergo adjuvant chemotherapy in one third of patients and decreased patients' decisional conflict.
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http://dx.doi.org/10.1007/s10549-020-05683-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275022PMC
July 2020

Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands.

Lancet Oncol 2020 06 30;21(6):750-751. Epub 2020 Apr 30.

Department of Research and Development, Netherlands Comprehensive Cancer Organisation, Utrecht 3511 DT, Netherlands; Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, Netherlands. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(20)30265-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252180PMC
June 2020

Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts.

Breast Cancer Res Treat 2020 Jun 11;181(2):423-434. Epub 2020 Apr 11.

Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC).

Methods: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope.

Results: The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula.

Conclusions: Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.
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http://dx.doi.org/10.1007/s10549-020-05611-8DOI Listing
June 2020

Quantifying the Mitigating Effects of Whole-Breast Radiotherapy and Systemic Treatments on Regional Recurrence Incidence Among Breast Cancer Patients.

Ann Surg Oncol 2020 Sep 20;27(9):3402-3411. Epub 2020 Mar 20.

Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands.

Background: Despite the potential for residual lymph node metastases after a negative or positive sentinel lymph node biopsy (SLNB), breast cancer patients rarely experience regional recurrences (RRs). This study aimed to quantify the effects of nonsurgical treatments on RR incidence among SLNB-negative (SLNB N0) breast cancer patients.

Methods: All primary SLNB N0-staged breast cancer patients with a diagnosis between 2005 and 2008 and 5-year follow-up data on recurrences were selected from the Netherlands Cancer Registry. The cumulative incidence function (CIF) for RR was calculated as the first event at 5 years, taking into account any other first-event (local or distant recurrence, contralateral breast cancer, or death) as competing risk. Cox regression analysis was used to model the cause-specific hazard of RR developing as the first event to quantify the effect of adjuvant systemic therapy and whole-breast radiotherapy (RT) on RR incidence at 5 years.

Results: The study included 13,512 patients. Of these patients, 162 experienced an RR. The CIF of RR at 5 years was 1.3% (95% confidence interval [CI], 1.1-1.5%), whereas the CIFs for death and other events were 4.4% and 9.5%, respectively. Cox regression analysis showed hazard ratios (HRs) of 0.46 (95% CI 0.33-0.64), 0.31 (95% CI 0.18-0.55), and 0.40 (95% CI 0.24-0.67) respectively for patients treated by RT as a routine part of breast-conserving therapy (BCT), chemotherapy, and hormonal therapy.

Conclusion: RT as routine part of BCT, chemotherapy, and hormonal therapy independently exerted a mitigating effect on the risk for the development of RR. The three methods at least halved the risk.
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http://dx.doi.org/10.1245/s10434-020-08356-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410865PMC
September 2020

Prediction and clinical utility of a contralateral breast cancer risk model.

Breast Cancer Res 2019 12 17;21(1):144. Epub 2019 Dec 17.

Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making.

Methods: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility.

Results: In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers.

Conclusions: We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.
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http://dx.doi.org/10.1186/s13058-019-1221-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918633PMC
December 2019

Association between initiation of adjuvant chemotherapy beyond 30 days after surgery and overall survival among patients with triple-negative breast cancer.

Int J Cancer 2020 07 28;147(1):152-159. Epub 2019 Nov 28.

Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22-2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84-1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted.
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http://dx.doi.org/10.1002/ijc.32788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317578PMC
July 2020

Quality of life among symptomatic compared to PSA-detected prostate cancer survivors - results from a UK wide patient-reported outcomes study.

BMC Cancer 2019 Oct 15;19(1):947. Epub 2019 Oct 15.

Northern Ireland Cancer Registry, Centre for Public Health, Queen's University Belfast, Mulhouse Building, Grosvenor Road, Belfast, BT12 6DP, Northern Ireland, UK.

Background: Quality of life among prostate cancer survivors varies by socio-demographic factors and treatment type received; however, less in known about differences in functional outcomes by method of presentation. We investigate differences in reported urinary, bowel, sexual and hormone-related problems between symptomatic and PSA-detected prostate cancer survivors.

Methods: A UK wide cross-sectional postal survey of prostate cancer survivors conducted 18-42 months post-diagnosis. Questions were included on presentation method and treatment. Functional outcome was determined using the EPIC-26 questionnaire. Reported outcomes were compared for symptomatic and PSA-detected survivors using ANOVA and multivariable log-linear regression.

Results: Thirty-five thousand eight hundred twenty-three men responded (response rate: 60.8%). Of these, 31.3% reported presenting via PSA test and 59.7% symptomatically. In multivariable analysis, symptomatic men reported more difficulty with urinary incontinence (Adjusted mean ratio (AMR): 0.96, 95% CI: 0.96-0.97), urinary irritation (AMR: 0.95, 95% CI: 0.95-0.96), bowel function (AMR: 0.97, 95% CI: 0.97-0.98), sexual function (AMR: 0.90, 95% CI: 0.88-0.92), and vitality/hormonal function (AMR: 0.96, 95% CI: 0.96-0.96) than PSA-detected men. Differences were consistent across respondents of differing age, stage, Gleason score and treatment type.

Conclusion: Prostate cancer survivors presenting symptomatically report poorer functional outcomes than PSA-detected survivors. Differences were not explained by socio-demographic or clinical factors. Clinicians should be aware that men presenting with symptoms are more likely to report functional difficulties after prostate cancer treatment and may need additional aftercare if these difficulties persist. Method of presentation should be considered as a covariate in patient-reported outcome studies of prostate cancer.
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http://dx.doi.org/10.1186/s12885-019-6164-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792209PMC
October 2019

Immediate Breast Reconstruction in The Netherlands and the United States: A Proof-of-Concept to Internationally Compare Quality of Care Using Cancer Registry Data.

Plast Reconstr Surg 2019 10;144(4):565e-574e

From the Division of Plastic and Reconstructive Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School; Division of Plastic and Reconstructive Surgery, Academic Medical Center Utrecht; Dutch Institute for Clinical Auditing; Department of Plastic and Reconstructive Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam; Department of Epidemiology and Preventive Medicine, Monash University; Division of Plastic and Reconstructive Surgery, Brigham and Women's Hospital; Department of Research, Netherlands Comprehensive Cancer Organization; Department of Health Technology and Services Research, University of Twente; Department of Plastic, Reconstructive and Hand Surgery, Maastricht UMC+; and Division of Plastic and Reconstructive Surgery, Medisch Spectrum Twente.

Background: Studies based on large-volume databases have made significant contributions to research on breast cancer surgery. To date, no comparison between large-volume databases has been made internationally. This is the first proof-of-concept study exploring the feasibility of combining two existing operational databases of The Netherlands and the United States, focusing on breast cancer care and immediate breast reconstruction specifically.313/291 METHODS:: The National Breast Cancer Organization The Netherlands Breast Cancer Audit (NBCA) (2011 to 2015) and the U.S. Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2013) were compared on structure and content. Data variables were grouped into general, treatment-specific, cancer-specific, and follow-up variables and were matched. As proof-of-concept, mastectomy and immediate breast reconstruction rates in patients diagnosed with invasive breast cancer or ductal carcinoma in situ were analyzed.

Results: The NBCA included 115 variables and SEER included 112. The NBCA included significantly more treatment-specific variables (n = 46 versus 6), whereas the SEER database included more cancer-specific variables (n = 74 versus 26). In patients diagnosed with breast cancer or ductal carcinoma in situ, immediate breast reconstruction was performed in 19.3 percent and 24.0 percent of the breast cancer cohort and 44.0 percent and 35.3 percent of the ductal carcinoma in situ cohort in the NBCA and SEER, respectively. Immediate breast reconstruction rates increased significantly over time in both data sets.

Conclusions: This study provides a first overview of available registry data on breast cancer care in The Netherlands and the United States, and revealed limited data on treatment in the United States. Comparison of treatment patterns of immediate breast reconstruction showed interesting differences. The authors advocate the urgency for an international database with alignment of (treatment) variables to improve quality of breast cancer care for patients across the globe.
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http://dx.doi.org/10.1097/PRS.0000000000006011DOI Listing
October 2019

Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

Oncologist 2020 01 12;25(1):e24-e30. Epub 2019 Sep 12.

Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.

Background: Studies have demonstrated worse breast cancer-specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account.

Materials And Methods: Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70-74 [reference group], 75-79, and ≥80 years) on recurrence risk.

Results: A total of 18,419 patients were included. Nine-year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70-74, 75-79, and ≥80 years, and 9-year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75-79 years remained at higher risk after adjustment for tumor and treatment characteristics (75-79 years subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.11-1.41; ≥80 years sHR, 1.03; 95% CI, 0.91-1.17).

Conclusion: Patients aged 75-79 years had a higher risk of distant recurrence than patients aged 70-74 years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer.

Implications For Practice: In this population-based study of 18,419 surgically treated patients aged 70 years or older, patients aged 75-79 years were at higher risk of distant recurrence than were patients aged 70-74 years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy.
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http://dx.doi.org/10.1634/theoncologist.2019-0412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964133PMC
January 2020