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Psychosocial Research and Epidemiology: Flora van Leeuwen

Flora Van Leeuwen Voor Publicatie

Flora van Leeuwen, Ph.D. professorGroup leader, Head of the division, Professor

About Flora van Leeuwen

Cancer epidemiology investigates the distribution of cancer frequency in human populations and studies determinants of cancer development and course of disease.
The Cancer Epidemiology group of NKI/AVL focuses on two principal research lines: (1) the assessment of the long‑term risks of second malignancy and cardiovascular disease following treatment of Hodgkin's lymphoma, breast cancer, testicular cancer and childhood malignancy; and (2) the assessment of the roles of and hormone-related and genetic risk factors in the etiology of breast,  ovarian and endometrial cancer. Special interest is in cancer etiology in BRCA1/2 families and the risks after subfertility treatment. Epidemiologic methods are combined with molecular analyses a) to examine gene-environment interactions, and b) to differentiate risk factors for cancer according to specific genetic alterations in the tumor.

Late effects of cancer treatment
Unfortunately, effective cancer treatments may also cause damage to healthy organs and  tissues.
Now that curative treatment is available for a substantial group of cancer patients, it is increasingly important to evaluate how the occurrence of late complications of treatment affects their long‑term survival. In the first research line we aim 1) to evaluate the long-term risk of second cancers following specific radiotherapy and/or chemotherapy regimens for Hodgkin's lymphoma (HL), non-Hodgkin lymphoma,  breast cancer, testicular cancer and childhood malignancies over a period of up to 40 years; 2) to similarly evaluate the risk of cardiovascular disease, taking into account both treatment factors and established cardiovascular risk factors such as smoking and hypertension; 3) to examine the separate and combined effects of radiation dose, chemotherapy regimen, premature menopause and genetic factors on the risks of breast cancer after HL and contralateral breast cancer; 4) to examine the effects of tamoxifen on the risk and prognosis of endometrial cancer after breast cancer; 5) to make an overall assessment of the influence of various treatments on the total burden of adverse events, as determined by the number of events and their severity. Recently, special focus is on the identification of genotypes associated with a stronger increase of radiation-induced cancer and anthracycline-associated heart disease.
To achieve these aims, we have available several large, mostly nationwide, cohorts of cancer patients with treatment data and complete follow-up: Hodgkin lymphoma (n=7000), testicular cancer (n=5000), breast cancer (n=10,000). Furthermore, in a nationwide implementation project we are setting up special outpatient clinics for screening of HL survivors on late effects; we will also use this infrastructure for research into subclinical late effects, screening efficacy and interventions, in order to reduce morbidity and mortality due to adverse treatment effects. With the BETTER consortium we are developing guidelines for screening and follow-up for survivors of both Hodgkin and non-Hodgkin lymphoma; adherence to screening guidelines by physicians and survivors will be examined as well as screening efficacy in terms of reduced morbidity and mortality.

The etiology of hormone-related cancers
The second research line focuses on the etiology and prognosis of female hormone-related cancers, i.e. cancers of the breast, ovary and uterus. We aim 1) to investigate known and suspected risk factors for breast cancer among BRCA1/2 carriers; 2) to build risk prediction models for BRCA1/2 carriers in which both genetic single nucleotide polymorphisms (SNPs) and reproductive or lifestyle risk factors are incorporated; 3) to examine cancer risk of women exposed to DES in utero and 4) to examine cancer risk of women exposed to ovarian stimulation for IVF; 5) to examine cancer risk in nurses, focused on shift work and risk of breast cancer; 6) to investigate the survival of sporadic breast cancer cases according to treatment and SNP profile.
To achieve these aims we are building a nationwide cohort of BRCA1/2 carriers (HEereditary Breast and Ovarian cancer study Netherlands, HEBON; n~5000) and closely collaborate internationally with other groups to increase the necessary statistical power. We coordinate the International BRCA1/2 Carrier Cohort Study (IBCCS; ~2,500 BRCA1 and ~3,000 BRCA2 carriers), an international prospective cohort study among BRCA1/2 carriers. In addition, we collaborate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA; n=37,000, 24,000 BRCA1 and 13,000 BRCA2), with DNA samples available and coordinate the hormonal/lifestyle risk factor part. Objectives 3 and 4 are examined in 2 nationwide cohorts of 12,000 DES daughters and 40,000 women who underwent subfertility treatment between 1980-2000 (30,000 women who received ovarian stimulation for IVF and 10,000 subfertile controls). In the latter nationwide project (OMEGA) all 13 IVF centers are participating. In de Nightingale cohort study we recruited 60,000 nurses to examine, among others, the effects of shift work and circadian rhythms on breast cancer risk (objective 5).  Objective 6 is achieved in a cohort of 5000 breast cancer patients treated 1975-2000. For all these patients extensive treatment data are available and DNA was isolated from paraffin-embedded tissue blocks.
All participants in the above mentioned cohorts have received web-based questionnaires about reproductive and lifestyle factors. 

Within this group there is an independent unit that is driven by: Matti Rookus, a Research Associate. Click here for more information about her group



Michael Schaapveld

Research associate


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Annelies Nijdam

Postdoctoral fellow


After a career as an IT professional, I trained as a veterinarian. To further myself in health sciences I pursued a Ph.D. in Clinical Epidemiology at the University Medical Center Utrecht. Wishing to apply my broad background and excellent communication skills, in December 2015 I joined the NKI-AVL to coordinate the BETER-project (Better care after Hodgkin lymphoma: Evaluation of long-term Treatment Effects and screening Recommendations). The goal of this project is to increase the life expectancy and enhance the quality of life of Hodgkin lymphoma survivors in the Netherlands by reducing morbidity and mortality from late adverse effects of treatment.


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Naomi Boekel MSc



In 2009 I obtained my Masters degree in Lifestyle and chronic disorders at VU Amsterdam. The ten-year survival of breast cancer is 70-75%, leading to a long life expectancy for the majority of patients. Now that curative treatment is available for so many breast cancer patients, it is increasingly important to evaluate how the occurrence of late adverse treatment sequelae affects their long‑term morbidity and mortality from diseases other than breast cancer. Therefore, the aim of my project is to assess the risk of cardiovascular disease in breast cancer survivors.

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Lara Terra

Ph.D. student


After my study medicine I started working as a clinician in the Department of Obstetrics
and Gynecology of Groene Hart Ziekenhuis in Gouda and in the Haags Medisch Centrum in The Hague and many knowledge gaps became apparent to me. The importance of research became very clear. Therefore I am very proud to be able to participate and do my part in the further development of
evidence-based health services. My research project is about the long-term health effects of prophylactic removal of the ovaries in young women (<45 years) with a high genetic risk of breast- and ovarian cancer. We focus on cardiovascular diseases, bone health, cognition and quality of life.

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Yvonne Geurts

Ph.D. Student


I obtained my Master degree in Biomedical Sciences at the Radboud University Nijmegen in 2017. During this training, I completed internships in cancer epidemiology and cancer immunology at the Cancer Council Victoria, Melbourne and the Center for Cancer Immune Therapy, Copenhagen. 

Since January 2018 I am working as a PhD-student at the department of Psychosocial research and Epidemiology in the group of Prof. dr. Flora van Leeuwen. I am working on the project: "Cardiotoxicity and second cancer risk after treatment of aggressive B-cell Non-Hodgkin lymphoma", which is funded by the Dutch Cancer Society.

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Mandy Spaan MSc

Ph.D. Student


In 2009 I obtained a Masters degree in Health Sciences at VU Amsterdam. Since May 2010 I work as a PhD student at the department of Psychosocial Research and Epidemiology. I am currently working on the OMEGA study. This is a large nationwide cohort study to examine whether women who received ovarian stimulation for in-vitro fertilization (IVF) treatments are at increased risk of developing hormone-related cancers, like breast and ovarian cancer.

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Sandra Fase, MSc

Research Assistant


I studied Pharmacy at Utrecht University with specialization in pharmacoepidemiology. At the NKI I collect data for the research projects on the late effects after the treatment of Hodgkin lymphoma and breast cancer, especially second malignancies and cardiovascular diseases. Therefore, I collect data from medical files and send questionnaires to general practitioners and cardiologists. By detecting late effects the treatment of cancer can be adapted in the future and screening can be intensified. I think it is very satisfying to contribute to the health of many people.

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Katinka John

Research Assistent


In 2017 I obtained my Master's degree in Health and Medical Psychology at Leiden
University. At the NKI I work as a research assistant for the Epidemiology Group. I collect data for research projects on the late effects after the treatment of breast cancer and Hodgkin lymphoma, especially cardiovascular diseases. Therefore, I send questionnaires to patients and collect data from
medical files. The detection of late effects after the treatment of cancer is  very important to improve treatments in the future. I am glad I can contribute to that.

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Dr. Sandra van de Belt



After passing my dietician examination, I joined PSOE as a research assistant in 1988. I participated in many projects of our Epidemiologic group (long-term health consequences of cancer treatment and the etiology of hormone-related female cancers). After graduating in Epidemiology, I coordinated a multicenter study on late effects of treatment for testicular cancer or Hodgkin's lymphoma, particularly the risk of second malignancies or cardiac disease, from 2002-2007. In 2009, I obtained my PhD-degree on this topic. Since 2007 I coordinate the OMEGA-study, a nationwide study on risk of hormone-related cancers (breast, ovary and endometrial cancer) after subfertility treatment.

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Key publications View All Publications

  • Genetic susceptibility to radiation-induced breast cancer after Hodgkin lymphoma

    Blood. 2019;133(10):1130-1139.

    Opstal-van Winden AWJ, de Haan HG, Hauptmann M, Schmidt MK,
    Broeks A, Russell NS, Janus CPM, Krol ADG, van der Baan FH, De Bruin ML, van
    Eggermond AM, Dennis J, Anton-Culver H, Haiman CA, Sawyer EJ, Cox A, Devilee P,
    Hooning MJ, Peto J, Couch FJ, Pharoah P, Orr N, Easton DF, Aleman BMP, Strong
    LC, Bhatia S, Cooke R, Robison LL, Swerdlow AJ, van Leeuwen FE

    Link to Pubmed
  • Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma

    (2015) NEJM. 373(26):2499

    Schaapveld  M, Aleman BMP, Van Eggermond AM, Janus CPM, Krol ADG, Van der Maazen RWM,  Roesink j, Raemaekers JMM, De Boer JP, Zijlstra JM, Van Imhoff GW, Petersen EJ,
    Poortmans PMP, Beijert M, Lybert ML, Mulder I, Visser O, Louwman MWJ, Krul IM,
    Lugtenburg P, Van Leeuwen FE

    Link to Pubmed

Recent publications View All Publications

  • All publications from Flora van Leeuwen

    Link to all publications in Pubmed
  • Risk of cancer in children and young adults conceived by assisted reproductive technology

    Hum Reprod. 2019

    Spaan M, van den Belt-Dusebout AW, van den Heuvel-Eibrink MM, Hauptmann M, Lambalk CB, Burger CW, van Leeuwen FE

    Link to Pubmed


  • Office manager

    Karin Roede & Danielle Groenewegen

  • E-mail

  • Telephone Number

    0031 20 512 2480



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