Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort

Yuehan Wang, Leontien C.M. Kremer, Flora E. Van Leeuwen, Gregory T. Armstrong, Wendy Leisenring, Florent De Vathaire, Melissa M. Hudson, Claudia E. Kuehni, Michael A. Arnold, Nadia Haddy, Charlotte Demoor-Goldschmidt, Ibrahima Diallo, Rebecca M. Howell, Matthew J. Ehrhardt, Chaya S. Moskowitz, Joseph P. Neglia, Helena J.H. Van Der Pal, Leslie L. Robison, Michael Schaapveld, Lucie M. TurcotteNicolas Waespe, Cécile M. Ronckers, Jop C. Teepen

Research output: Contribution to journalArticlepeer-review

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PURPOSE: The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age.

PARTICIPANTS: The consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis.

FINDINGS TO DATE: This is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts' follow-up started 1951-1981 and ended 2013-2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0-32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5-11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0-40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively.

FUTURE PLANS: The consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future.

Original languageEnglish (US)
Article number065910
JournalBMJ open
Issue number11
StatePublished - Nov 7 2022

Bibliographical note

Funding Information:
This work was supported by the Children Cancer Free Foundation (KiKa, Grant No. 325 title: Risk factors for female breast cancer after treatment for childhood and adolescent cancer: individual patient data analyses of an internationally pooled cohort; CMR, FEvL, LCMK, principal investigators). The CCSS and SJLIFE cohorts are supported by the National Cancer Institute (CA55727, GTA, principal investigator; CA195547, MMH and LLR, principal investigators) as well as support to St. Jude Children’s Research Hospital also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, principal investigator) and the American Lebanese Syrian Associated Charities (ALSAC). The NWTSG was supported by the National Cancer Institute (CA054498, N.E. Breslow and WL, principal investigator). The DCCSS LATER is supported by the Dutch Cancer Society (DCOG2011-5027, CMR, FEvL, Wim Tissing, principal investigators and UVA2012-5517, CMR, LCMK, principal investigators). The FCCSS is funded by the Fondation ARC (PopHARC Grant) and the Agence Nationale pour la Recherche Médicale (ANR, Hope-Epi Grant). The SCCSS has been supported by the Swiss Cancer League and the Swiss Cancer Research foundation (KFS-02783-02-2011, KLS-3412-02-2014, KFS-4157-02-2017, KLS/KFS-4825-01-2019; KFS-4722-02-2019, KFS-5027-02-2020; KFS-5302-02-2021; KLS-5432-08-2021), Kinderkrebs Schweiz ( and Kinderkrebshilfe Schweiz ( The DHL has been supported by Dutch Cancer Society (NKI 2010-4720).

Funding Information:
Clinical practice guidelines for providers have been developed to promote optimal health-related outcomes by screening survivors. In 2010, the International Late Effects of Childhood Cancer Guideline Harmonisation Group (IGHG) was established ( ) to harmonise the guidelines available worldwide, according to a common methodology. In 2012, the IGHG formulated recommendations for breast cancer surveillance among high-risk groups, to which an update was recently published. As part of the harmonisation methodology, the expert group identified gaps in knowledge by specifying clinical questions for which empirical evidence was deemed insufficient to affect or alter recommendations for clinical practice. For this reason, we established the International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer funded by the Children Cancer Free Foundation (KiKa, Grant No. 325), to conduct individual patient data analyses. Initially, the consortium aimed to address three knowledge gaps regarding subsequent breast cancer identified in the IGHG breast cancer guidelines: (1) to explore the effects of prescribed radiation dose and radiation field, as a proxy for exposed tissue volume, on the risk of subsequent breast cancer; (2) to examine the role of anthracyclines and the contributions of single anthracycline drugs regarding risk of subsequent breast cancer and (3) to evaluate whether relative and absolute excess risks of subsequent breast cancer remain increased across lifespan, especially after age 50 years.

Publisher Copyright:
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


  • Paediatric oncology
  • Paediatric radiotherapy
  • Cancer Survivors
  • Humans
  • Risk Factors
  • Antineoplastic Agents/therapeutic use
  • Child, Preschool
  • Male
  • Incidence
  • Young Adult
  • Breast Neoplasms/epidemiology
  • Neoplasms/therapy
  • Adolescent
  • Female
  • Adult
  • Neoplasms, Second Primary/diagnosis
  • Child
  • Cohort Studies

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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