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Epidemiology

Breast cancer risk among thyroid cancer survivors and the role of I-131 treatment

British Journal of Cancer volume 127, pages 2118–2124 (2022)Cite this article

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Abstract

Background

Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial.

Methods

We pooled individual data of women who were treated for differentiated thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models.

Results

Of 8475 women (mean age at diagnosis: 45 years, range 2–90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36–1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84–1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI −4 to 13) and 42 (95% CI −8 to 93) excess breast cancer cases per 10,000 person-years, respectively.

Conclusions

An elevated risk was observed for the highest cumulative administered activity (>=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors.

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Data availability

The data underlying this paper will be shared upon reasonable request to the corresponding author.

Code availability

The code used to generate results that are reported in the paper will be shared on reasonable request to the corresponding author.

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Acknowledgements

We would like to thank Dr. Carine Corone for her contribution on the setting up of the study at the Rene Huguenin Center.

Funding

Thi-Van-Trinh TRAN received a doctoral grant from the Paris Sud-Paris Saclay University. Michel Henry-Amar is supported by the French National League Against Cancer (LNC). This study was supported by grants from the European Commission (Concerted action no. FI4P-CT98-0078, DG 12-WSMN), and European Community’s Seventh Framework Program (EURATOM) contract Fission-269553 (EpiRadBio), and by the Epidemiology Commission of Electricity of France (EDF). Role of funders: The funders do not have any role in the conception and the analysis of the study nor in the writing or the article.

Author information

Authors and Affiliations

  1. Radiation Epidemiology Team, INSERM U1018, Center for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif Cedex, France

    Thi-Van-Trinh Tran, Carole Rubino, Rodrigue Allodji, Ibrahima Diallo, Jérome Garsi, Neige Journy & Florent de Vathaire

  2. Department of Research, Gustave Roussy, F-94805, Villejuif Cedex, France

    Thi-Van-Trinh Tran, Carole Rubino, Rodrigue Allodji, Ibrahima Diallo, Jérome Garsi, Neige Journy & Florent de Vathaire

  3. University of Paris Saclay, Kremlin-Bicêtre, France

    Thi-Van-Trinh Tran, Carole Rubino, Rodrigue Allodji, Ibrahima Diallo, Jérome Garsi, Neige Journy & Florent de Vathaire

  4. Department of Nuclear Medicine, Sant’Anna Hospital, via Napoleona 60, 22100, Como, Italy

    Milena Andruccioli

  5. Department of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, Caen, France

    Stéphane Bardet

  6. Department of Diagnostic Imaging, Nuclear Medicine Unit, Perugia General Hospital, Perugia, Italy

    Massimo Dottorini

  7. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65, Stockholm, Sweden

    Per Hall

  8. Department of Oncology, Södersjukhuset, 118 83, Stockholm, Sweden

    Per Hall

  9. Centre de Traitement des Données du Cancéropôle Nord-Ouest, Plateforme de Recherche Clinique Ligue Contre le Cancer, Centre François Baclesse, 3 Avenue Général Harris, 14076, Caen, Cedex 5, France

    Michel Henry-Amar

  10. Laboratoire d’Évaluation de la Dose Interne, Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSE-SANTE/SDOS/LEDI, 31 avenue de la Division Leclerc, 92260, Fontenay-aux-Roses, France

    Stephanie Lamart

  11. Institut Curie Saint-Cloud, 92210, Saint-Cloud, France

    Françoise Le Thai

  12. Department of Research and Development, Region Halland, Halmstad, Sweden

    Stefan Lönn

  13. Department of Physics, Gustave Roussy and Paris Saclay University, Villejuif, France

    Marcel Ricard

  14. Nuclear medicine-thyroid Unit, Institut Godinot, 1, rue du Général-Koenig, 51100, Reims, France

    Claire Schvartz

  15. Thyroid Cancer Registry of Marne-Ardennes, Institut Godinot, 1, rue du Général-Koenig, 51100, Reims, France

    Claire Schvartz

  16. Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Saclay, 94800, Villejuif, France

    Martin Schlumberger

Authors
  1. Thi-Van-Trinh Tran
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  2. Carole Rubino
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  3. Rodrigue Allodji
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  9. Per Hall
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  10. Michel Henry-Amar
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  18. Florent de Vathaire
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Contributions

Study conception and design: FDV, CR, TTVT, MS, MD, PH, SL and ID. Statistical analysis: TTVT, CR, FDV and NJ. writing of the original draft: TTVT. Interpretation of the results: FDV, TTVT, CR, NJ and MS. All authors revised the paper and approved the final version.

Corresponding authors

Correspondence to Thi-Van-Trinh Tran, Carole Rubino or Florent de Vathaire.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The French cohort’s protocol has been approved by the French National Agency regulating Data Protection (CNIL), and consent was obtained from the study participants. The Swedish cohort obtained approval from the Swedish data inspection board. Because the sole aim of the Italian cohort is to evaluate the safety of radio-iodine treatment administered by medical doctors of this hospital, without any other specific contact with patients, no special authorization has been needed for this population. The pooled cohort study contains only pseudonymized individual data.

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Tran, TVT., Rubino, C., Allodji, R. et al. Breast cancer risk among thyroid cancer survivors and the role of I-131 treatment. Br J Cancer 127, 2118–2124 (2022). https://doi.org/10.1038/s41416-022-01982-5

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