Association of Silicone Breast Implants With Overall Wellbeingand Auto-immune Diseases

NCT05400954 | Unknown

• 1 other identifier: M21REO
• Study Type: observational
• Target: 15,000
• Locations: 1 country
• Sites: 7

Brief Summary

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 breast implants in the development of so called 'breast implant illness' and autoimmune diseases in breast cancer survivors with a silicone breast implant-based reconstruction. Breast implant illness is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. Methods/Design: The Areola study is a multi-centre historic cohort study with prospective follow-up aiming to assess the risk of 'breast implant illness' and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. The cohort consists of breast cancer survivors who received surgical treatment with silicone implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As 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 still alive will be invited to complete a web-based questionnaire covering various health related topics. The entire cohort including deceased women will be linked to the population based computerized databases of Statistics Netherlands. These databases include a registry of diagnostic codes, a pharmacotherapeutic prescriptions registry and a cause-of-death registry in which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and the prevalence and incidence of 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 breast implant illness 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. Keywords: Silicone breast implants, Breast reconstruction, Breast cancer, Breast Implant Illness, Autoimmune disease

Conditions

Breast Cancer; Breast Implant; Complications; Autoimmune Diseases

Keywords

Silicone Breast Implant; Breast Reconstruction; Breast Cancer; Breast Implant Illness; Autoimmune disease

Outcome Measures

Primary Outcomes (3)

• Breast Implant Illness

  Relative risk (RR) of experiencing the following complaints in exposed and comparison groups: Cognitive impairment joint pain myalgia anxiety feeling depressed skin rashes weakness sleeping problems headache hair loss food intolerances and allergies numbness/tingling in upper and lower limbs dry eyes morning stiffness night sweats heart palpitations shoulder pain

  20years

• Autoimmune disease

  Relative risk (RR) and Incidence rate (IR) for the following illnesses in exposed group and comparison group: Sjögren's Syndrome (SjS) Rheumatoid Arthritis (RA) Systemic Lupus Erythematosus (SLE) Systemic Sclerosis (SSc), Mixed Connective Tissue Disease (MCTD) Antiphospholipid Syndrome (APS) Ankylosing Spondylitis Sarcoidosis Multiple Sclerosis (MS) hypothyroidism hyperthyroidism psoriatic disease inflammatory bowel disease fibromyalgia chronic fatigue syndrome irritable bowel syndrome

  20years

• Relative risk to develop autoimmune diseases and BII complaints associated with certain risk factors:

  RR for BII and autoimmune diseases will be assessed associated with riskfactors in the domains of demographics, lifestyle, reproductive history, medical- and treatment history and family history. Furthermore the influence of psychosocial factors like satisfaction with the breasts and self-esteem on BII risk are evaluated.

  20years

Study Arms (3)

Reconstruction with silicone breast implant

The cohort will be composed of women who underwent surgery for first invasive breast cancer or ductal carcinoma in situ (DCIS) in the years 2000 to 2015 in the collaborating centres. Eligible for inclusion in the exposed group are all women who underwent (i) mastectomy followed by immediate implant-based reconstruction, (ii) mastectomy followed by implant-based reconstruction at a later stage and (iii) latissimus dorsi flap reconstruction with a silicone breast implant

Procedure: Breast reconstruction with silicone breast implant

Breast cancer surgery without silicone breast implant

. Eligible for inclusion in the comparison group are women who underwent (i) simple mastectomy without reconstruction, (ii) autologous reconstruction and (iii) breast conserving surgery. From the latter group a frequency-matched sample will be selected based on age at breast cancer diagnosis and calendar year of diagnosis.

Procedure: Breast conserving surgery/Mastectomy/Autologous reconstruction

cosmetic breast augmentation

. Women who underwent cosmetic augmentation in the years 2000 to 2015 constitute a second comparison group. From this group a frequency-matched sample will be selected based on age and year of surgery.

Procedure: Breast Augmentation

Interventions

Breast reconstruction with silicone breast implant PROCEDURE

(i) mastectomy followed by immediate implant-based reconstruction, (ii) mastectomy followed by implant-based reconstruction at a later stage and (iii) latissimus dorsi flap reconstruction with a silicone breast implant.

Also known as: Breast Reconstruction

Reconstruction with silicone breast implant

Breast conserving surgery/Mastectomy/Autologous reconstruction PROCEDURE

(iv) simple mastectomy without reconstruction, (v) autologous reconstruction and (vi) breast conserving surgery,

Breast cancer surgery without silicone breast implant

Breast Augmentation PROCEDURE

(vii) cosmetic augmentation with silicone breast implants

cosmetic breast augmentation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women who underwent surgery for first invasive breast cancer or ductal carcinoma in situ (DCIS) in the years 2000 to 2015 in the collaborating centres. Eligible for inclusion in the exposed group are all women who underwent (i) mastectomy followed by immediate implant-based reconstruction, (ii) mastectomy followed by implant-based reconstruction at a later stage and (iii) latissimus dorsi flap reconstruction with a silicone breast implant. Eligible for inclusion in the comparison group are women who underwent (i) simple mastectomy without reconstruction, (ii) autologous reconstruction and (iii) breast conserving surgery. From the latter group a frequency-matched sample will be selected based on age at breast cancer diagnosis and calendar year of diagnosis. Women who underwent cosmetic augmentation in the years 2000 to 2015 constitute a second comparison group. From this group a frequency-matched sample will be selected based on age and year of surgery.

You may qualify if:

• surgery for first invasive breast cancer or ductal carcinoma in situ (DCIS) in the years 2000 to 2015 in the collaborating centres

You may not qualify if:

• above the age of 60 at breast cancer diagnosis
• Not residing in Netherlands

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Erasmus Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• Zuyderland Medical Centre: collaborator
• Medisch Spectrum Twente: collaborator
• Ziekenhuisgroep Twente: collaborator
• Velthuis Kliniek: collaborator

Study Sites (7)

Zuyderland Medical Center

Heerlen, Limburg, Netherlands

Location

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Location

Netherlands Cancer Institute Antoni van Leeuwenhoek

Amsterdam, North Holland, Netherlands

Location

Velthuis Kliniek

Hilversum, North Holland, Netherlands

Location

Ziekenhuisgroep Twente

Almelo, Overijssel, Netherlands

Location

Medisch Spectrum Twente

Enschede, Overijssel, Netherlands

Location

Erasmus MC University Medical Center

Rotterdam, South Holland, Netherlands

Location

Related Publications (4)

• Spoor J, de Jong D, van Leeuwen FE. [Silicone breast implants: the importance of nuanced reporting]. Ned Tijdschr Geneeskd. 2022 Mar 21;166:D6515. Dutch.

  PMID: 35499539 BACKGROUND

• Spoor J, de Jong D, van Leeuwen FE. Silicone Particle Migration: A Misleading Report. Aesthet Surg J. 2022 Mar 15;42(4):NP261-NP262. doi: 10.1093/asj/sjab377. No abstract available.

  PMID: 34695179 BACKGROUND

• Spoor J, Mureau MAM, Tissier RLM, Hommes J, Rakhorst H, de Boer M, Oldenburg HSA, Heuts EM, Vissers YLJ, Dassen AE, Evers DJ, Koppert LB, Zaal LH, Linn SC, de Jong D, van der Hulst RRWJ, Vrancken Peeters MTFD, Bleiker EMA, van Leeuwen FE. Breast implant illness after reconstruction with silicone breast implants. J Natl Cancer Inst. 2025 Aug 1;117(8):1717-1728. doi: 10.1093/jnci/djaf136.

  PMID: 40605595 DERIVED

• Spoor J, Mureau MAM, Hommes J, Rakhorst H, Dassen AE, Oldenburg HSA, Vissers YLJ, Heuts EM, Koppert LB, Zaal LH, van der Hulst RRWJ, Vrancken Peeters MTFD, Bleiker EMA, van Leeuwen FE; AREOLA Collaboration. The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions. Ann Epidemiol. 2023 Jun;82:16-25. doi: 10.1016/j.annepidem.2023.04.001. Epub 2023 Apr 6.

  PMID: 37028614 DERIVED

Related Links

• Website RIVM: Onderzoeksprogramma vrouwen met een siliconen borstimplantaat

MeSH Terms

Conditions

Breast Neoplasms; Autoimmune Diseases

Interventions

Mammaplasty; Mastectomy, Segmental

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cosmetic Techniques; Therapeutics; Plastic Surgery Procedures; Surgical Procedures, Operative; Mastectomy

Study Officials

• Floor van Leeuwen, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

• Marie-Jeanne Vrancken Peeters, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

• Eveline Bleiker

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 2, 2022
• Study Start: July 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2025
• Last Updated: April 28, 2023

Record last verified: 2023-04

Locations

NL (7)