Biological Sciences Division
Published March 31, 2025 | Version v1
Journal article Open

Treatment, toxicity, and mortality after subsequent breast cancer in female survivors of childhood cancer

Creators

  • 1. University of Minnesota
  • 2. Mayo Clinic Arizona
  • 3. University of Kansas
  • 4. Northwestern Medicine Lake Forest Hospital
  • 5. University of Texas Southwestern Medical Center
  • 6. St. Jude Children's Research Hospital
  • 7. Children's Hospital Colorado
  • 8. Nationwide Children's Hospital
  • 9. Memorial Sloan Kettering Cancer Center
  • 10. University of Chicago
  • 11. Duke University

Description

Childhood cancer survivors, particularly those who received chest radiotherapy, are at high risk for developing subsequent breast cancer. Minimizing long-term toxicity risks associated with additional radiotherapy and chemotherapy is a priority, but therapeutic tradeoffs have not been comprehensively characterized and their impact on survival is unknown. In this study, 431 female childhood cancer survivors with subsequent breast cancer from a multicenter retrospective cohort study were evaluated. Compared with one-to-one matched females with first primary breast cancer, survivors are as likely to be prescribed guideline-concordant treatment (N = 344 pairs; survivors: 94%, controls: 93%), but more frequently undergo mastectomy (survivors: 81%, controls: 60%) and are less likely to be treated with anthracyclines (survivors: 47%, controls: 66%) or radiotherapy (survivors: 18%, controls: 61%). Despite this, survivors have nearly 3.5-fold (95% CI = 2.17-5.57) greater mortality risk. Here, we show survivors with subsequent breast cancer face excess mortality despite therapeutic tradeoffs and require specialized treatment guidelines.

Data availability

The Childhood Cancer Survivor Study is a US National Cancer Institute funded resource (U24 CA55727) to promote and facilitate research among long-term survivors of cancer diagnosed during childhood and adolescence. CCSS data are publicly available on dbGaP at https://www.ncbi.nlm.nih.gov/gap/ (accession number phs001327.v2.p1) and on the St. Jude Survivorship Portal within the St. Jude Cloud at https://survivorship.stjude.cloud/. Those interested in using this resource are encouraged to visit http://ccss.stjude. The deidentified, processed data used in this study have been deposited in a public repository (https://doi.org/10.5281/zenodo.14989624). The raw data are protected and are not available due to data privacy laws. All remaining data supporting the findings of this study can be found in the Article, Supplementary Material files and Source Data file. Source data are provided with this paper.

All code packages are publicly available and include: survival (https://cran.r-project.org/web/packages/survival/index.html), survminer (https://cran.r-project.org/web/packages/survminer/index.html), and ggplot2 (https://cran.r-project.org/web/packages/ggplot2/index.html).

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Additional details

Identifiers

DOI
10.1038/s41467-025-58434-w
Other
oai:uchicago.tind.io:14842

Funding

U.S. National Cancer Institute
K08 CA234232
U.S. National Cancer Institute
U24 CA55727
American Lebanese Syrian Associated Charities
U.S. National Cancer Institute
R21 CA261833
U.S. National Cancer Institute
P30 CA008748

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine, Pediatrics