Jelle Wesseling

Netherlands Cancer Institute · Division of Molecular Pathology

Background: Although DCIS is a precursor of invasive breast cancer (IBC), most DCIS lesions never will progress. As we cannot distinguish reliably progressive from harmless DCIS yet, almost all women with DCIS are treated extensively with surgery and often adjuvant radiotherapy or endocrine treatment, implying overtreatment of many thousands of wom...

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5–10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this q...

When locally advanced breast cancer is treated with neoadjuvant chemotherapy, the recurrence risk is significantly higher if no complete pathologic response is achieved. Identification of the underlying resistance mechanisms is essential to select treatments with maximal efficacy and minimal toxicity. Here we employed gene expression profiles deriv...

PURPOSE Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative...

Background Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. Purpose To assess the performance and clinical utility of mammographic radiomic features in the prediction of occ...

Purpose: Extensive work in pre-clinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages a...

Although ductal carcinoma in situ (DCIS) is a non-obligate precursor to ipsilateral invasive breast cancer (iIBC), most DCIS lesions remain indolent. Hence, overdiagnosis and overtreatment of DCIS is a major concern. There is an urgent need for prognostic markers that can distinguish harmless from potentially hazardous DCIS. We hypothesised that fe...

Window studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy for treatment response. Immunohistochemistry (IHC)-based Ki67 on tissue from neo-adjuvant trials was previously reported to be predictive for long-term response to endocrin...

Background Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to a...

Purpose To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a pr...

The COVID-19 pandemic forced the Dutch national breast screening program to a halt in week 12, 2020. In week 26, the breast program was resumed at 40% capacity, which increased to 60% in week 34. We examined the impact of the suspension and restart of the screening program on the incidence of screen-detected and non-screen-detected breast cancer. W...

As ongoing trials study the safety of an active surveillance strategy for low-risk ductal carcinoma in situ (DCIS), there is a need to explain why particular choices regarding treatment strategies are made by eligible women as well as their oncologists, what factors enter the decision process, and how much each factor affects their choice. To measu...

Purpose The presence of extensive ductal carcinoma in situ (DCIS) adjacent to HER2-positive invasive breast cancer (IBC) is often a contra-indication for breast-conserving surgery, even in case of excellent treatment response of the invasive component. Data on the response of DCIS to neoadjuvant systemic treatment (NST) are limited. Therefore, we e...

Background Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort. Methods The...

Objective To investigate whether BIRADS MRI characteristics before or during neoadjuvant endocrine therapy (NET) are associated with the preoperative endocrine prognostic index (PEPI) in ER+/HER2- breast cancer patients. Methods This retrospective observational cohort study included 35 ER+/HER2- patients with 38 tumors (3 bilateral cases) treated...

Importance: Primary analysis of the TRAIN-2 study showed high pathologic complete response rates after neoadjuvant chemotherapy with or without anthracyclines plus dual ERBB2 (formerly HER2) blockade. Objective: To evaluate 3-year event-free survival (EFS) and overall survival (OS) of an anthracycline-free and anthracycline-containing regimen wi...

Background Many cT3 breast cancer patients are treated with mastectomy, regardless of response to neoadjuvant systemic therapy (NST). We evaluated local control of cT3 patients undergoing breast-conserving therapy (BCT) based on magnetic resonance imaging (MRI) evaluation post-NST. In addition, we analyzed predictive characteristics for positive ma...

PurposeResults from active surveillance trials for ductal carcinoma in situ (DCIS) will not be available for > 10 years. A model based on real-world data (RWD) can demonstrate the comparative impact of non-intervention for women with low-risk features.Methods Multi-state models were developed using Surveillance, Epidemiology, and End Results Progra...

Background The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of...

Pure ductal carcinoma in situ (DCIS) is being diagnosed more frequently through breast screening programmes and is associated with an increased risk of developing invasive breast cancer. We assessed the clonal relatedness of 143 cases of pure DCIS and their subsequent events using a combination of whole exome, targeted and copy number sequencing, s...

Advances in tissue analysis methods, image analysis, high-throughput molecular profiling, and computational tools increasingly allow us to capture and quantify patient-to patient variations that impact cancer risk, prognosis, and treatment response. Statistical models that integrate patient-specific information from multiple sources (e.g., family h...

The prognostic value of cytonuclear grade in ductal carcinoma in situ (DCIS) is debated, partly due to high interobserver variability and the use of multiple guidelines. The aim of this study was to evaluate interobserver agreement in grading DCIS between Dutch, British, and American pathologists. Haematoxylin and eosin‐stained slides of 425 women...

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with breast cancer is associated with improved survival. Further assessment of the extent of residual disease, using the pathological anatomic American Joint Committee on Cancer staging method (ypStage) or the Residual Cancer Burden (RCB) method, have be...

Introduction The COVID-19 pandemic led to a significant drop in the incidence of cancer diagnoses in the Netherlands, partially due to the suspension of all national cancer screening programs on 16th March 2020 (week 12). Hospitals were forced to focus on care for COVID-19 patients resulting in limited capacity and down scaling of health care for n...

Background Pertuzumab greatly improves pathologic complete response (pCR) rates in early stage HER2-positive breast cancer. Long-term benefit of pertuzumab, however, is less well established, as follow-up of the NEOSPHERE and APHINITY trials did not show clear improvement in overall survival, although patients with high risk of recurrence (e.g. nod...

Background: Achieving a pathologic complete response (pCR) has been shown on the patient level to predict excellent long-term event-free survival outcomes. Residual cancer burden (RCB) quantifies the extent of residual disease for patients who did not achieve pCR. We have previously observed in the I-SPY 2 TRIAL that while metastatic events outside...

Background Predicting breast cancer recurrence in patients aged ≥70 years is challenging, as they generally have more indolent tumors and a higher chance of dying of competing causes than younger patients. The 70-gene signature test (MammaPrint) has been shown to accurately predict recurrence in women with early breast cancer and up to 3 positive l...

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 upsurg...

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, acco...

PurposeFor optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk.Methods...

Importance For women with a 20% or more familial risk of breast cancer without a known BRCA1/2 (BRCA1, OMIM 113705; and BRCA2, OMIM 114480) or TP53 (OMIM 151623) variant, screening guidelines vary substantially, and cost-effectiveness analyses are scarce. Objective To assess the cost-effectiveness of magnetic resonance imaging (MRI) screening stra...

Background: We previously showed that BRCA-like profiles can be used to preselect individuals with the highest risk of carrying BRCA mutations but could also indicate which patients would benefit from double-strand break inducing chemotherapy. A simple, robust, and reliable assay for clinical use that utilizes limited amounts of formalin-fixed, pa...

Objectives To investigate whether contralateral parenchymal enhancement (CPE) on MRI during neoadjuvant endocrine therapy (NET) is associated with the preoperative endocrine prognostic index (PEPI) of ER+/HER2− breast cancer.Methods This retrospective observational cohort study included 40 unilateral ER+/HER2− breast cancer patients treated with NE...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas...

Background Better understanding of the molecular biology associated with MRI phenotypes may aid in the diagnosis and treatment of breast cancer. Purpose To discover the associations between MRI phenotypes of breast cancer and their underlying molecular biology derived from gene expression data. Materials and Methods This is a secondary analysis of...

501 Background: The multicenter phase III TRAIN-2 study showed high pathological complete response (pCR) rates after neoadjuvant chemotherapy with and without anthracylines plus dual HER2-blockade in stage II-III HER2-positive breast cancer patients (67% vs 68%, p = 0.95) (NCT01996267). Here we report 3-year efficacy and safety outcomes. Methods: P...

To the Editor We read with interest the Viewpoint by Morrow and Winer considering the need for surgery in diagnoses ranging from ductal carcinoma in situ (DCIS) to postneoadjuvant invasive breast cancer.¹ These are 2 very different clinical situations, so here we consider in more detail the situation for DCIS. Arguing against active surveillance, M...

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management frame...

h3> Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. In this study, we refined a previously identified 111-gene outcome prediction-classifier, revealing FEN1 as the strongest determining factor in ERα-positive patie...

Introduction: The burden of the COVID-19 pandemic forced the Dutch health care services to discontinue their national screening programs on 16 March 2020 (week 12). For breast cancer, the program invites women aged 50–74 years for biennial screening mammography. From mid-June 2020 (week 25) the breast cancer screening program was resumed, albeit wi...

Introduction: Ductal Carcinoma In Situ (DCIS) is a proliferation of neoplastic cells confined to the ducto-lobular system. Due to uncertainty which DCIS lesions progress to invasive breast cancer women with DCIS receive surgery and radiotherapy. The PRECISION (PREvent ductal carcinoma In Situ Invasive Overtreatment Now) initiative intends to improv...

Purpose The majority of ‘low-risk’ (grade I/II) Ductal Carcinoma In Situ (DCIS) lesions do not progress to invasive breast cancer during a woman’s lifetime. Therefore, the safety of active surveillance versus standard surgical treatment for grade I/II DCIS is being evaluated in several clinical trials. If active surveillance is proven safe and impl...

Background: The incidence of ductal carcinoma in situ (DCIS) has greatly increased since the introduction of mammographic screening. However, so far, it is still not possible to predict which patient with DCIS will further develop invasive breast cancer. Adipocyte hypertrophy and adipocyte inflammation has been associated with increased risk of dev...

Background: The large favorable stage shift, that MRI screening causes as comared with mammograhy has been ublished recently in Lancet Oncology as well as the disadvantage of more false-ositive results with MRI. Here we want to resent the first results of cost and effectiveness. Methods: In twelve Dutch hositals, 1355 women aged 30-55 years with a...

Background: Recent studies have demonstrated independent validation of the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. However, a pooled subject-level analysis of multiple cohorts is needed to determine estimates of long-term prognosis for each class of RCB in each phenotypic subtype of breast cancer (BC) to...

Intra‐tumour heterogeneity fuels carcinogenesis and allows circumventing specific targeted therapies. HER2 gene amplification is associated with poor outcome in invasive breast cancer. Heterogeneous HER2 amplification has been described in 5‐41% of breast cancers. Here, we investigated the genetic differences between HER2‐positive and HER2‐negative...

Background: We conducted a prospective cohort study in the Netherlands (RAPCHEM: NCT01279304, BOOG 2010-03) in breast cancer (BC) patients treated with primary systemic therapy (PST), followed by surgery and post-operative radiation therapy (RT) according to a predefined consensus-based study-guideline (SG). The aim of the current analysis is to e...

Objective The majority of ‘low-risk’ (grade I/II) Ductal Carcinoma In Situ (DCIS) may not progress to invasive breast cancer during a women’s lifetime. Therefore, the safety of active surveillance versus standard surgical treatment for DCIS is prospectively being evaluated in clinical trials. If proven safe and selectively implemented in clinical p...

Purpose The future of non-operative management of DCIS relies on distinguishing lesions requiring treatment from those needing only active surveillance. More accurate preoperative staging and grading of DCIS would be helpful. We identified determinants of upstaging preoperative breast biopsies showing ductal carcinoma in situ (DCIS) to invasive bre...

Purpose: To retrospectively explore the relation between parenchymal enhancement of the healthy contralateral breast on dynamic contrast-enhanced magnetic resonance imaging (MRI) and genomic tests for estrogen receptor (ER)-pathway activity in patients with ER-positive/HER2-negative cancer. Methods: A subset of 227 consecutively included patient...