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Psychosocial Research and Epidemiology: Flora van Leeuwen

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

About Flora van Leeuwen

Introduction
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. 

Subgroup
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

Co-workers

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Dr. Annemieke Opstal-van Winden

Postdoctoral fellow

Experience

I am an epidemiologist with a special interest in breast cancer. I studied Health Sciences atMaastrichtUniversityand I received my Ph.D. at Utrecht University (UMCU) in 2010 on research into proteomics in breast cancer. Currently, I work on the KWO grant of Prof. dr. Floor van Leeuwen on late effects of treatment for Hodgkin's lymphoma. Within this project I focus on aspects related to the elevated risk for breast cancer in female Hodgkin's lymphoma survivors who received mediastinal radiation before age 40. I also investigate the late effects of premature menopause in Hodgkin's lymphoma survivors.

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Drs. Miranda Gerritsma

Research Assistant

Experience

As a research assistant I work on several different projects. These are projects of the Epidemiology Group as well as the Psychosocial Group. I support the different projects in their data collection by recruiting respondents, administering questionnaires / interviews and collecting the data from medical files.

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Ir. Harmke Groot

Ph.D. student

Experience

I completed my MSc. degree in Nutrition and Health atWageningenUniversityin 2009. I subsequently worked as a junior researcher atWageningenUniversityand as a data manager at NKI-AVL.

In 2012, I started as a PhD-student on the project "Long-term risk of cardiovascular disease and second malignancies after platinum-based chemotherapy for testicular cancer" which is funded by the Dutch Cancer Society. We will investigate the evolution of second malignancies and cardiovascular disease over time, and their separate and joint effect on mortality.

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Dr. Sandra van de Belt

Postdoc

Experience

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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Anja van Eggermond MSc

Ph.D. student

Experience

After obtaining a Bachelor's degree in Medical Imaging and Radiotherapy Techniques at Hogeschool INHOLLAND Haarlem, I obtained a Master degree in Health Sciences from the VU University Amsterdam. My background in radiotherapy and research led to a PhD project at the NKI. The main aim of this project is to evaluate the long-term risks of second cancer and cardiovascular disease following treatment of Hodgkin's lymphoma between 1965 and 1995. Special focus is on breast cancer and colorectal cancer as a second malignancy, third malignancies, cause-specific mortality, and total burden of late effects from Hodgkin's lymphoma treatment.

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Sandra Fase, MSc

Research Assistant

Experience

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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Inge Krul MSc

Ph.D. student

Experience

The aim of my PhD-project is to evaluate the long-term effects of treatment in female Hodgkin lymphoma (HL) survivors. These women have an increased risk of a premature menopause and breast cancer. I examine the long-term effects of a therapy-induced premature menopause on bone mineral density, cardiovascular status, neurocognitive functioning and quality of life. In addition, I evaluate the effectiveness of breast cancer screening in female HL survivors since current guidelines are prescribing annual BC screening by MRI and mammography, starting 8 years after treatment.   
I have a Master's degree in Health Sciences from the VU university Amsterdam.

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Mandy Spaan MSc

Ph.D. Student

Experience

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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Naomi Boekel MSc

Ph.D. Student

Experience

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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Driessen, Yvonne

Yvonne Driessen-Ruwaard

Office Manager

Experience

The function of office manager on this division is a duo job.

The division of Psychosocial Research and Epidemiology conducts research on the psychosocial and somatic effects of cancer and cancer treatment, and the risk factors for cancer.

Together with the other office manager, we support the researchers from the division with administrative and organizing tasks. We arrange appointments and meetings and coordinate the ordering of materials and central organization of computer facilities.
We assist group leaders within the division, among other things, with publications, grant proposals and annual reports.

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Key publications View All Publications

  • 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 et al.

    Link to Pubmed
  • Radiation Dose-Response Relationship for Risk of Coronary Heart Disease in Survivors of Hodgkin Lymphoma

    (2016) J Clin Oncol. 34(3):235.

    van Nimwegen FA, Schaapveld M, Cutter DJ, Janus CP, Krol AD, Hauptmann M, Kooijman K, Roesink J, van der Maazen R, Darby SC, Aleman et al.

    Link to Pubmed
 
 

Recent publications View All Publications

  • Risk and prognostic significance of metachronous contralateral testicular germ cell tumours

    (2012) British Journal of Cancer 107(9):1637-43.

    Schaapveld M, van den Belt-Dusebout AW, Gietema JA, de Wit R, Horenblas S, Witjes JA, Hoekstra HJ, Kiemeney LA, Louwman WJ, Ouwens GM,...

    Link to Pubmed
  • Risk of valvular heart disease after tretment for Hodgkin Lymphoma

    (2015) J Natl Cancer Inst; 107(4): djv008

    Cutter DJ, Schaapveld M, Darby SC, Hauptmann M, van Nimwegen FA, Krol ADG, Janus CPM, Van Leeuwen FE, Aleman BMP

    Link to Pubmed
 

Contact

  • Office manager

    Yvonne Driessen-Ruwaard & Danielle Groenewegen

  • E-mail

    secretariaat.PSOE@nki.nl

  • Telephone Number

    0031 20 512 2480

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