The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions

Jonathan Spoor, Marc A.M. Mureau, On behalf of the AREOLA Collaboration, Juliëtte Hommes, Hinne Rakhorst, Anneriet E. Dassen, Hester S.A. Oldenburg, Yvonne L.J. Vissers, Esther M. Heuts, Linetta B. Koppert, Laura H. Zaal, Rene R.W.J. van der Hulst, Marie Jeanne T.F.D. Vrancken Peeters, Eveline M.A. Bleiker, Flora E. van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


Background: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called “breast implant illness” (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. Methods: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. Discussion: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. Registration: This study is registered at on June 2, 2022 (NCT05400954).

Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalAnnals of Epidemiology
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
This study is funded by the Ministry of Health , Welfare and Sports of the Netherlands / National Institute for Public Health and the Environment (Parnassusplein 5, 2511 VX, The Hague, The Netherlands). The funding body had and will have, no role in the design of this study, collection, analysis, and interpretation of data. Manuscripts are reviewed by the National Institute for Public Health and the Environment before submission for publication.

Publisher Copyright:
© 2023 Elsevier Inc.


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