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Risk of primary breast cancer in patients with differentiated thyroid cancer undergoing radioactive iodine therapy: a systematic review and meta-analysis

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Although it has been proven that radioactive iodine (RAI) treatment is an effective and well-tolerated procedure in patients with differentiated thyroid cancer (DTC), there is still some concern regarding the risk of developing a second primary malignancy after RAI administration. We performed a systematic review and meta-analysis to investigate the risk of primary breast cancer in patients with DTC undergoing RAI therapy.

Methods

A comprehensive literature search of the PubMed, Scopus, and Web of Science databases was conducted according to the PRISMA statement.

Results

The final analysis included 14 studies accounting for a total of 200,247 patients with DTC (98,368 treated with RAI and 101,879 not treated with RAI). The relative risk of primary breast cancer in patients with DTC treated with RAI to those not treated with RAI among studies ranged from 0.45 to 2.55, the pooled relative risk was 0.83 (95% confidence interval, 0.70–0.99), and the heterogeneity was 71.5%.

Conclusion

The present meta-analysis indicates that patients with DTC treated with RAI do not have a higher risk of primary breast cancer compared to those not treated with RAI. These findings suggest that RAI therapy does not increase the risk of breast cancer.

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Data Availability

The manuscript represents valid work, and neither this manuscript nor one with substantially similar content under the same authorship has been published or is being considered for publication elsewhere.

Code availability

Not applicable.

References

  1. Luster M, Pfestroff A, Hänscheid H, Verburg FA. Radioiodine therapy. Semin Nucl Med. 2017;47:126–34.

    Article  Google Scholar 

  2. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1–133.

    Article  Google Scholar 

  3. Schlumberger M, Leboulleux S. Current practice in patients with differentiated thyroid cancer. Nat Rev Endocrinol. 2021;17:176–88.

    Article  CAS  Google Scholar 

  4. Tulchinsky M, Binse I, Campennì A, Dizdarevic S, Giovanella L, Jong I, et al. Radioactive iodine therapy for differentiated thyroid cancer: lessons from confronting controversial literature on risks for secondary malignancy. J Nucl Med. 2018;59:723–5.

    Article  Google Scholar 

  5. Teng CJ, Hu YW, Chen SC, Yeh CM, Chiang HL, Chen TJ, Liu CJ. Use of radioactive iodine for thyroid cancer and risk of second primary malignancy: a nationwide population-based study. J Natl Cancer Inst. 2015;108(2):djv314.

    Article  Google Scholar 

  6. Lin CY, Lin CL, Huang WS, Kao CH. Risk of breast cancer in patients with thyroid cancer receiving or not receiving 131I treatment: a nationwide population-based cohort study. J Nucl Med. 2016;57:685–90.

    Article  CAS  Google Scholar 

  7. Zhang Y, Liang J, Li H, Cong H, Lin Y. Risk of second primary breast cancer after radioactive iodine treatment in thyroid cancer: a systematic review and meta-analysis. Nucl Med Commun. 2016;37:110–5.

    Article  CAS  Google Scholar 

  8. Chen AY, Levy L, Goepfert H, Brown BW, Spitz MR, Vassilopoulou-Sellin R. The development of breast carcinoma in women with thyroid carcinoma. Cancer. 2001;92:225–31.

    Article  CAS  Google Scholar 

  9. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  Google Scholar 

  10. Wells G, Shea B, O'Connell D, Robertson J, Peterson J, Welch V, et al. The Newcastle‐Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta‐analyses. 2013. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 26 July 2021.

  11. Megens MR, Churilov L, Thijs V. New-onset atrial fibrillation after coronary artery bypass graft and long-term risk of stroke: a meta-analysis. J Am Heart Assoc. 2017;6:e007558.

    Article  Google Scholar 

  12. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97–111.

    Article  Google Scholar 

  13. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  Google Scholar 

  14. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. Chichester: Wiley; 2008.

    Book  Google Scholar 

  15. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  Google Scholar 

  16. Hall P, Holm LE, Lundell G, Rudén BI. Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients. Acta Oncol. 1992;31:403–7.

    Article  CAS  Google Scholar 

  17. Dottorini ME, Lomuscio G, Mazzucchelli L, Vignati A, Colombo L. Assessment of female fertility and carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma. J Nucl Med. 1995;36:21–7.

    CAS  PubMed  Google Scholar 

  18. Adjadj E, Rubino C, Shamsaldim A, Le MG, Schlumberger M, de Vathaire F. The risk of multiple primary breast and thyroid carcinomas. Cancer. 2003;98:1309–17.

    Article  Google Scholar 

  19. Rubino C, De Vathaire F, Dottorini ME, Hall P, Schvartz C, Couette JE, et al. Second primary malignancies in thyroid cancer patients. Br J Cancer. 2003;89:1638–44.

    Article  CAS  Google Scholar 

  20. Bhattacharyya N, Chien W. Risk of second primary malignancy after radioactive iodine treatment for differentiated thyroid carcinoma. Ann Otol Rhinol Laryngol. 2006;115:607–10.

    Article  Google Scholar 

  21. Lang BH, Wong IO, Wong KP, Cowling BJ, Wan KY. Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy. Surgery. 2012;151:844–50.

    Article  Google Scholar 

  22. Ahn HY, Min HS, Yeo Y, Ma SH, Hwang Y, An JH, et al. Radioactive iodine therapy did not significantly increase the incidence and recurrence of subsequent breast cancer. J Clin Endocrinol Metab. 2015;100:3486–93.

    Article  CAS  Google Scholar 

  23. De Souza MC, Momesso DP, Vaisman F, Vieira Neto L, Martins RA, Corbo R, et al. Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer? Arch Endocrinol Metab. 2016;60:9–15.

    Article  Google Scholar 

  24. Kuo JH, Chabot JA, Lee JA. Breast cancer in thyroid cancer survivors: an analysis of the Surveillance, Epidemiology, and End Results-9 database. Surgery. 2016;159:23–9.

    Article  Google Scholar 

  25. Hirsch D, Shohat T, Gorshtein A, Robenshtok E, Shimon I, Benbassat C. Incidence of nonthyroidal primary malignancy and the association with (131)I treatment in patients with differentiated thyroid cancer. Thyroid. 2016;26:1110–6.

    Article  CAS  Google Scholar 

  26. Silva-Vieira M, Carrilho Vaz S, Esteves S, Ferreira TC, Limbert E, Salgado L, et al. Second primary cancer in patients with differentiated thyroid cancer: does radioiodine play a role? Thyroid. 2017;27:1068–76.

    Article  CAS  Google Scholar 

  27. Drozd V, Schneider R, Platonova T, Panasiuk G, Leonova T, Oculevich N, et al. Feasibility study shows multicenter, observational case-control study is practicable to determine risk of secondary breast cancer in females with differentiated thyroid carcinoma given radioiodine therapy in their childhood or adolescence; findings also suggest possible fertility impairment in such patients. Front Endocrinol. 2020;11:567385.

    Article  Google Scholar 

  28. Mei X, Yao X, Feng F, Cheng W, Wang H. Risk and outcome of subsequent malignancies after radioactive iodine treatment in differentiated thyroid cancer patients. BMC Cancer. 2021;21:543.

    Article  CAS  Google Scholar 

  29. Cappagli V, Caldarella A, Manneschi G, Piaggi P, Bottici V, Agate L, et al. Nonthyroidal second primary malignancies in differentiated thyroid cancer patients: is the incidence increased comparing to the general population and could it be a radioiodine therapy consequence? Int J Cancer. 2020;147:2838–46.

    Article  CAS  Google Scholar 

  30. Sawka AM, Thabane L, Parlea L, Ibrahim-Zada I. Second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis. Thyroid. 2009;19:451–7.

    Article  CAS  Google Scholar 

  31. Higgins JP. Commentary: Heterogeneity in meta-analysis should be expected and appropriately quantified. Int J Epidemiol. 2008;37:1158–60.

    Article  Google Scholar 

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Funding

Open access funding provided by Università degli Studi di Napoli Federico II within the CRUI-CARE Agreement.

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Authors and Affiliations

Authors

Contributions

CN, MK, MP, and AC conceptualized the project; VC, RG, LP, FV, and SM carried out the literature search, screened the studies for appropriateness, and performed a second-step selection of the selected full-published reports based on the eligibility criteria; VC, RG, and MP performed the analyses and prepared the figures, CN, MK, MP, and AC drafted the manuscript, and all the authors revised and critically commented on the paper and approved the final version of the manuscript.

Corresponding author

Correspondence to Alberto Cuocolo.

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Not applicable for a systematic review.

Conflict of interest

The authors declare no competing interests.

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This article is part of the Topical Collection on Endocrinology.

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Nappi, C., Klain, M., Cantoni, V. et al. Risk of primary breast cancer in patients with differentiated thyroid cancer undergoing radioactive iodine therapy: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 49, 1630–1639 (2022). https://doi.org/10.1007/s00259-021-05625-4

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  • DOI: https://doi.org/10.1007/s00259-021-05625-4

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