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Molecular Pathology: Jelle Wesseling


Jelle Wesseling, M.D. Ph.D.Groupleader

About Jelle Wesseling

Research interest: Breast Cancer Biomarkers

Breast cancer is a heterogeneous disease ranging from being non-hazardous to life threatening. Accurate pathological and molecular analyses are key to make accurate predictions regarding prognosis and response to treatment. Therefore, we aim to find, validate, and implement biomarkers to make more precise and personalized predictions regarding prognosis and response to treatment.

Finding the balance between over- and undertreatment of breast Ductal Carcinoma In Situ (DCIS)

We try to find the balance between overdiagnosis and undertreatment of low-risk Ductal Carcinoma in Situ (DCIS). The rise in DCIS incidence due to screening has not resulted in a decrease of breast cancer related mortality. This implies that part of the DCIS lesions detected by population-based screening can be considered as overdiagnosis, putting many women at risk of overtreatment. Therefore, more accurate discrimination of low- vs. high-risk DCIS lesions is warranted. We aim to identify subsets of DCIS patients with a very low risk of developing an invasive ipsilateral breast cancer (BC) to define possible alternative treatment strategies for this subgroup of very low risk DCIS tumors, such as a wait and see policy.
 Retrospectively, we are performing both epidemiological and molecular pathology studies on a population-based cohort of 10,090 women treated for DCIS, with long time follow-up available. Prospectively, we initiated a randomized controlled, trial to evaluate the safety of active surveillance in 1240 women with LOw-Risk DCIS (LORD). This trial is coordinated by the BOOG and EORTC.

Development of clinically useful molecular tests to predict chemotherapy response of primary breast cancers

Within the neoadjuvant chemotherapy program, we aim to develop tests predicting response to preoperative chemotherapy. Since 2004 we collect pre-treatment biopsy material from all patients scheduled to receive neoadjuvant chemotherapy in the NKI-AVL. In addition, we precisely collect all clinical and pathological data of the patients, resulting in a database with over 1,400 patients registered, and from most of them biopsies for translational research are available, as well as resection specimens in case of remaining disease at surgery. In the past years we made significant progress in our search for biomarkers. Highlights are the association between a BRCA-like genomic profile and a remarkably better response to high dose chemotherapy. To assess this BRCA-like genomic profile in routine diagnostics we developed an easy to perform MLPA assay (collaboration with Petra Nederlof). We now started to compare somatic mutations, copy number alterations and gene expression levels between 'before' and 'after' chemotherapy samples from the same patient, to study the effect of chemotherapy on breast tumors and to identify potential resistance mechanisms.
Within this research line we collaborate intensively with the computational biology group of Lodewyk Wessels and with the medical oncology department (Sjoerd Rodenhuis, Gabe Sonke).

Furthermore, we are collaborating with Paula Elkhuizen, Astrid Scholten, Marc van de Vijver, and Harry Bartelink to find biomarkers determining breast cancer radiosensitivity.

The research of the Wesseling group is supported by grants from the Dutch Cancer Society/Alpe d'Huez, Pink Ribbon, A Sister's Hope and NWO-ZonMw.


Almekinders, Mathilde

Mathilde Almekinders, MD, MSc

Ph.D. Student and pathologist


In 2010 I obtained my medical degree and master of Biomedical Sciences at Leiden University. I completed my training as a pathologist in 2015 at Leiden University Medical center (LUMC).

Currently I work as a PhD student in the group of Jelle Wesseling and as a pathologist at the department of Pathology. My research focuses on the immune microenvironment of ductal carcinoma in situ (DCIS) aiming at the identification of biomarkers that can predict the biological behavior of DCIS in order to optimize individualized diagnosis and treatment.  

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Sophie Bosma

MD, Ph.D. Student


My name is Sophie Bosma. I graduated from medical school in 2012. Currently, I am a PhD student radiotherapy. After 2 years of fulltime research, I will combine my work as a graduate student with a residency in radiation oncology.
The main subject of my research is radiosensitivity and local recurrences in breast cancer. I will work on the 'PAPBI trial' and the 'Young boost trial' among other projects.



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Lotte Elshof, M.D.

Ph.D. Student


Since March 2012, I have been working at the NKI-AVL starting as a doctor on the surgical ward and as Ph.D. student. My research is focused on finding the balance between overdiagnosis and undertreatment of Ductal Carcinoma in Situ of the breast.





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Esther H. Lips, Ph.D.

Associate Staff Scientist


As a staff scientist in the Wesseling group my main focus is on developing prognostic and predictive tests for breast cancer. First, I am involved in finding biomarkers for neoadjuvant chemotherapy sensitivity. Second, I am involved in our translational DCIS research, where we aim to find and implement biomarkers for DCIS risk stratification. Third, I am developing  and implementing next generation sequencing techniques for diagnostic purposes.




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Michiel de Maaker, Ing.



In august 2012, I started as technician on the Young Boost trial.
The main objective of the trial is to compare the effect of a high boost dose (26 Gy) with a low boost dose (16 Gy) in breast conserving therapy, on the local recurrence rate.
 Additional objectives are:
To test the genotypic and phenotypic profiles of breast tumors in young patients with invasive breast cancer, and its relation to:
a. Local recurrence after breast conserving treatment
b. Lymph node metastases
c. Distant metastases and survival
d. Radio sensitivity
e. Age

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Mulder, Lennart.jpg

Lennart Mulder, BASc



I studied Biology and Medical Laboratory Research at the University of Applied Sciences Leiden, where I obtained a bachelor's degree in Molecular Biology Cum Laude. Since 2006, I am employed as a research technician at the Netherlands Cancer Institute. Currently, I am involved in several clinical trials focused on preoperative chemotherapy for patients with breast cancer. The main goal of these trials is to develop molecular based tests to predict chemotherapy response in these patients.



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Petra Kristel, Ing.



I finished my technician education at the Amsterdam Univeristy of Applied Sciences in 1991. My first job was at the Academic Medical Center for 3 years. In 1994, I started working at the Netherlands Cancer Institute, eventually at the Molecular Pathology department. The main topic of our group is breast cancer. Since 2007 I am working for Jelle Wesseling. I always enjoyed working on several projects with PhD students, post-docs and others technicians.



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Van Ramshorst, Mette

Mette van Ramshorst, M.D.

Ph.D. Student


After graduating from medical school in 2012, I was a resident for one year at the medical oncology department of the Netherlands Cancer Institute. In March 2013, I started as a PhD student at the medical oncology/molecular pathology department. The coming years I will focus on optimizing neoadjuvant systemic treatment in HER2-positive breast cancer. Finding predictive biomarkers for response to neoadjuvant systemic treatment is one of the aims of my research.




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Visser, Lindy

Lindy L. Visser, MSc.

Ph.D. Student


August 2013, I achieved a master degree in Oncology at VU University Amsterdam. Today, I'm a PhD student studying ductal carcinoma in situ (DCIS) of the breast. Population-based breast cancer screening and implementation of digital mammography has resulted in an increased incidence of DCIS, but not in a decreased incidence of advanced breast cancer, suggesting overtreatment of DCIS lesions. Within this study I'm aiming to find biomarkers to distinguish harmless from aggressive lesions. Subsequently, these accurate biomarkers may aid to decide which woman should be treated and which one not, which creates the potential of sparing these patients intensive treatment.


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Key publications View All Publications

  • Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response

    (2015) Breast Cancer Res. Oct 3;17(1):134. doi: 10.1186/s13058-015-0642-8.

    Lips EH, Michaut M, Hoogstraat M, Mulder L, Besselink NJ, Koudijs MJ, Cuppen E, Voest EE, Bernards R, Nederlof PM, Wesseling J, Rodenhuis et al.

    Link to PubMed
  • Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study

    (2015) Eur J Cancer. Aug;51(12):1497-510. doi: 10.1016/j.ejca.2015.05.008. Epub 2015 May 26.

    Elshof LE, Tryfonidis K, Slaets L, van Leeuwen-Stok AE, Skinner VP, Dif N, Pijnappel RM, Bijker N, Rutgers EJ, Wesseling J.

    Link to PubMed

Recent publications View All Publications

  • Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups

    (2016) Breast Cancer Res. Oct 18;18(1):104.

    Abubakar M, Orr N, Daley F, Coulson P, Ali HR, Blows F, Benitez J, Milne R, Brenner H, Stegmaier C, Mannermaa A, Chang-Claude J, Rudolph...

    Link to PubMed
  • Finding the balance between over- and under-treatment of ductal carcinoma in situ (DCIS)

    (2016) Breast. Sep 23. pii: S0960-9776(16)30162-X. doi: 10.1016/j.breast.2016.09.001. [Epub ahead of print]

    Groen EJ, Elshof LE, Visser LL, Rutgers EJ, Winter-Warnars HA, Lips EH, Wesseling J.

    Link to PubMed


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