Breast cancer: screening, stage, and outcome:Studies based on the Netherlands Cancer Registry

This thesis provides a comprehensive description of the impact of the Dutch screening programme on breast cancer stage, the surgical procedures and the long term outcomes up to 10 year after diagnosis. In this thesis, data of the Netherlands Cancer Registry were used, which were linked to data of the Netherlands Breast Cancer Screening Programme. This theses shows that the screening programme resulted in the detection of less advanced stage cancers, even when different definitions of advanced stage were used and taking a certain amount of overdiagnosis into account. Furthermore, women with screen-detected cancer had a similar risk of having positive margins after breast conserving surgery compared to women with clinically detected breast cancer. Also, the two main treatment options for small breast cancers (cT1-2,N0), breast conserving therapy or mastectomy, resulted in a similar survival after 10 years. Additionally, this thesis shows that some women attended the screening programme while they still received outpatient follow-up in the hospital. The current recommendations in the Dutch guideline for follow-up after these first 5 years are age-based. This thesis shows that these age categories use suboptimal age cut-offs that do not correspond well to the actual risk for recurrence. This could be improved by choosing alternative age cut-offs and including other factors that have an impact on the risk for recurrence as well. These new insights add to further improvement of early diagnosis and to help personalise patient care with the most suitable treatment and follow-up

Transparantie van indicatoren in de oncologie: voor wie en waarom?

In Nederland is er steeds meer aandacht voor transparantie in de gezondheidszorg. Indicatoren kunnen hiertoe een belangrijke bijdrage leveren. Het zijn meetbare elementen van de zorgverlening die een indicatie geven over de kwaliteit van de zorgverlening

Prolonged screening interval due to the COVID-19 pandemic and its association with tumor characteristics and treatment; a register-based study from BreastScreen Norway

Objective: During the COVID-19 pandemic Norway had to suspend its national breast cancer screening program. We aimed to investigate the effect of the pandemic-induced suspension on the screening interval, and its subsequent association with the tumor characteristics and treatment of screen-detected (SDC) and interval breast cancer (IC). Methods: Information about women aged 50–69, participating in BreastScreen Norway, and diagnosed with a SDC (N = 3799) or IC (N = 1806) between 2018 and 2021 was extracted from the Cancer Registry of Norway. Logistic regression was used to investigate the association between COVID-19 induced prolonged screening intervals and tumor characteristics and treatment. Results: Women with a SDC and their last screening exam before the pandemic had a median screening interval of 24.0 months (interquartile range: 23.8–24.5), compared to 27.0 months (interquartile range: 25.8–28.5) for those with their last screening during the pandemic. The tumor characteristics and treatment of women with a SDC, last screening during the pandemic, and a screening interval of 29–31 months, did not differ from those of women with a SDC, last screening before the pandemic, and a screening interval of 23–25 months. ICs detected 24–31 months after screening, were more likely to be histological grade 3 compared to ICs detected 0–23 months after screening (odds ratio: 1.40, 95% confidence interval: 1.06–1.84). Conclusions: Pandemic-induced prolonged screening intervals were not associated with the tumor characteristics and treatment of SDCs, but did increase the risk of a histopathological grade 3 IC. This study provides insights into the possible effects of extending the screening interval

Long-term effects of the interruption of the Dutch breast cancer screening program due to COVID-19:A modelling study

Due to COVID-19, the Dutch breast cancer screening program was interrupted for three months with uncertain long-term effects. The aim of this study was to estimate the long-term impact of this interruption on delay in detection, tumour size of screen-detected breast cancers, and interval cancer rate. After validation, the micro-simulation model SiMRiSc was used to calculate the effects of interruption of the breast cancer screening program for three months and for hypothetical interruptions of six and twelve months. A scenario without interruption was used as reference. Outcomes considered were tumour size of screen-detected breast cancers and interval cancer rate. Women of 55–59 and 60–64 years old at time of interruption were considered. Uncertainties were estimated using a sensitivity analysis. The three-month interruption had no clinically relevant long-term effect on the tumour size of screen-detected breast cancers. A 19% increase in interval cancer rate was found between last screening before and first screening after interruption compared to no interruption. Hypothetical interruptions of six and twelve months resulted in larger increases in interval cancer rate of 38% and 78% between last screening before and first screening after interruption, respectively, and an increase in middle-sized tumours in first screening after interruption of 26% and 47%, respectively. In conclusion, the interruption of the Dutch screening program is not expected to result in a long-term delay in detection or clinically relevant change in tumour size of screen-detected cancers, but only affects the interval cancer rate between last screening before and first screening after interruption

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

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

The method of detection of ductal carcinoma in situ has no therapeutic implications: results of a population-based cohort study

Multivariable-adjusted Cox regression analysis of ipsilateral and contralateral invasive breast cancer in women aged 49–75 years at DCIS diagnosis (DCIS diagnostic period 1989–2004). Age was the primary time scale, time since DCIS diagnosis (0–5, 5–10, and ≥10 years) the secondary time scale, and DCIS treatment a time-varying covariable (DOCX 22 kb

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

Background: After 5 years of annual follow-up following breast cancer, Dutch guidelines are age based: annual follow-up for women &lt;60 years, 60–75 years biennial, and none for &gt;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 &lt;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 &lt;50, 50–69, and &gt; 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.</p

Correlation between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases after Neoadjuvant Systemic Therapy

Objective:The aim was to investigate whether pathologic complete response (PCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with neoadjuvant systemic therapy (NST) for different breast cancer subtypes.Background:Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast PCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well.Methods:Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pa