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^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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

Funding

LMT, JPN, YY, and LLR designed the study and developed the concept. CI and LMT provided supervision for the study. CI, ES, SM, RR, JS, HW, AJM, VN, MAA, MRC, GTA, RN, KCO, JPN, AB, and LMT collected the data. CI, HH, ZL, and LMT prepared and analyzed the data. YY and CSM provided insights regarding statistical interpretation. CI and LMT drafted the manuscript. Funding for this project was acquired by LMT, LLR, and GTA. All authors including LGS and TOM contributed critical revisions and approved the final manuscript for publication. This work was funded by the US National Cancer Institute (K08 CA234232, LM Turcotte, principal investigator; U24 CA55727, GT Armstrong, principal investigator) and the American Lebanese Syrian Associated Charities. Support to C Im was provided by NCI R21 CA261833. Support to CS Moskowitz was provided by NCI P30 CA008748.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

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

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10.1038/s41467-025-58434-w

Cite this

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

@article{a8ca0c1a236d4d8ea2a3a6fae9a29197,

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

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.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

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

language = "English (US)",

volume = "16",

journal = "Nature communications",

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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

TY - JOUR

T1 - Treatment, toxicity, and mortality after subsequent breast cancer in female survivors of childhood cancer

AU - Im, Cindy

AU - Hasan, Hasibul

AU - Stene, Emily

AU - Monick, Sarah

AU - Rader, Ryan K.

AU - Sheade, Jori

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

Y1 - 2025/12

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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U2 - 10.1038/s41467-025-58434-w

DO - 10.1038/s41467-025-58434-w

M3 - Article

C2 - 40164623

AN - SCOPUS:105001514580

SN - 2041-1723

VL - 16

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3088

ER -

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

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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