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

Cindy Im, Hasibul Hasan, Emily Stene, Sarah Monick, Ryan K. Rader, Jori Sheade, Heather Wolfe, Zhanni Lu, Logan G. Spector, Aaron J. McDonald, Vikki Nolan, Michael A. Arnold, Miriam R. Conces, Chaya S. Moskowitz, Tara O. Henderson, Leslie L. Robison, Gregory T. Armstrong, Yutaka Yasui, Rita Nanda, Kevin C. Oeffinger, Joseph P. Neglia, Anne Blaes and Lucie M. Turcotte ()
Additional contact information
Cindy Im: University of Minnesota
Hasibul Hasan: University of Minnesota
Emily Stene: University of Minnesota
Sarah Monick: Mayo Clinic Arizona
Ryan K. Rader: University of Kansas
Jori Sheade: Lurie Cancer Center Affiliate Network
Heather Wolfe: University of Texas Southwestern Medical Center
Zhanni Lu: University of Minnesota
Logan G. Spector: University of Minnesota
Aaron J. McDonald: St. Jude Children’s Research Hospital
Vikki Nolan: St. Jude Children’s Research Hospital
Michael A. Arnold: Anschutz Medical Campus
Miriam R. Conces: Nationwide Children’s Hospital
Chaya S. Moskowitz: Memorial Sloan Kettering Cancer Center
Tara O. Henderson: University of Chicago
Leslie L. Robison: St. Jude Children’s Research Hospital
Gregory T. Armstrong: St. Jude Children’s Research Hospital
Yutaka Yasui: St. Jude Children’s Research Hospital
Rita Nanda: University of Chicago
Kevin C. Oeffinger: Duke University
Joseph P. Neglia: University of Minnesota
Anne Blaes: University of Minnesota
Lucie M. Turcotte: University of Minnesota

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58434-w

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