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; Lucie M. Turcotte

doi:10.1038/s41467-025-58434-w

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. OeffingerJoseph P. Neglia, Anne Blaes, Lucie M. Turcotte

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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.

Original language	English (US)
Article number	3088
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-58434-w
State	Published - Dec 2025

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Publisher Copyright:
© The Author(s) 2025.

PubMed: MeSH publication types

Journal Article
Multicenter Study

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Im, C., Hasan, H., Stene, E., Monick, S., Rader, R. K., Sheade, J., Wolfe, H., Lu, Z., Spector, L. G., McDonald, A. J., Nolan, V., Arnold, M. A., Conces, M. R., Moskowitz, C. S., Henderson, T. O., Robison, L. L., Armstrong, G. T., Yasui, Y., Nanda, R., ... Turcotte, L. M. (2025). Treatment, toxicity, and mortality after subsequent breast cancer in female survivors of childhood cancer. Nature communications, 16(1), Article 3088. https://doi.org/10.1038/s41467-025-58434-w

Im, C, Hasan, H, Stene, E, Monick, S, Rader, RK, Sheade, J, Wolfe, H, Lu, Z , Spector, LG, McDonald, AJ, Nolan, V, Arnold, MA, Conces, MR, Moskowitz, CS, Henderson, TO, Robison, LL, Armstrong, GT, Yasui, Y, Nanda, R, Oeffinger, KC, Neglia, JP , Blaes, A & Turcotte, LM 2025, 'Treatment, toxicity, and mortality after subsequent breast cancer in female survivors of childhood cancer', Nature communications, vol. 16, no. 1, 3088. https://doi.org/10.1038/s41467-025-58434-w

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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.",

author = "Cindy Im and Hasibul Hasan and Emily Stene and Sarah Monick and Rader, {Ryan K.} and Jori Sheade and Heather Wolfe and Zhanni Lu and Spector, {Logan G.} and McDonald, {Aaron J.} and Vikki Nolan and Arnold, {Michael A.} and Conces, {Miriam R.} and Moskowitz, {Chaya S.} and Henderson, {Tara O.} and Robison, {Leslie L.} and Armstrong, {Gregory T.} and Yutaka Yasui and Rita Nanda and Oeffinger, {Kevin C.} and Neglia, {Joseph P.} and Anne Blaes and Turcotte, {Lucie M.}",

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doi = "10.1038/s41467-025-58434-w",

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AU - Wolfe, Heather

AU - Lu, Zhanni

AU - Spector, Logan G.

AU - McDonald, Aaron J.

AU - Nolan, Vikki

AU - Arnold, Michael A.

AU - Conces, Miriam R.

AU - Moskowitz, Chaya S.

AU - Henderson, Tara O.

AU - Robison, Leslie L.

AU - Armstrong, Gregory T.

AU - Yasui, Yutaka

AU - Nanda, Rita

AU - Oeffinger, Kevin C.

AU - Neglia, Joseph P.

AU - Blaes, Anne

AU - Turcotte, Lucie M.

PY - 2025/12

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

PubMed: MeSH publication types

UN SDGs

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