TY - JOUR
T1 - Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer
AU - Wang, Yuehan
AU - Ronckers, C. cile M.
AU - van Leeuwen, Flora E.
AU - Moskowitz, Chaya S.
AU - Leisenring, Wendy
AU - Armstrong, Gregory T.
AU - de Vathaire, Florent
AU - Hudson, Melissa M.
AU - Kuehni, Claudia E.
AU - Arnold, Michael A.
AU - Demoor-Goldschmidt, Charlotte
AU - Green, Daniel M.
AU - Henderson, Tara O.
AU - Howell, Rebecca M.
AU - Ehrhardt, Matthew J.
AU - Neglia, Joseph P.
AU - Oeffinger, Kevin C.
AU - van der Pal, Helena J. H.
AU - Robison, Leslie L.
AU - Schaapveld, Michael
AU - Turcotte, Lucie M.
AU - Waespe, Nicolas
AU - Kremer, Leontien C. M.
AU - Teepen, Jop C.
AU - van Leeuwen, Flora E.
AU - de Vathaire, Florent
AU - van der Pal, Helena J. H.
AU - Haddy, Nadia
AU - Diallo, Ibrahima
AU - Baker, K. Scott
AU - de González, Amy Berrington
AU - Conces, Miriam R.
AU - Constine, Louis S.
AU - Hawkins, Mike
AU - Loonen, Jacqueline J.
AU - Louwerens, Marloes
AU - Janssens, Geert O.
AU - Mellemkjaer, Lene
AU - Reulen, Raoul
AU - Winther, Jeanette F.
N1 - Funding Information: This work was supported by the Children Cancer Free Foundation (KiKa; grant 325 title: risk factors for female breast cancer after treatment for childhood and adolescent cancer: individual patient data analyses of an internationally pooled cohort) to C.M.R., F.E.v.L., L.C.M.K. (principal investigators). The CCSS and SJLIFE cohorts are supported by the National Cancer Institute (CA55727 to G.T.A. (principal investigator) and CA195547 to M.M.H. and K.K.N. (principal investigators)) as well as support to St. Jude Children’s Research Hospital also provided by the Cancer Center Support (CORE) grant (CA21765 to C.R. (principal investigator)) and the American Lebanese-Syrian Associated Charities (ALSAC). The NWTSG was supported by the National Cancer Institute (CA054498 to N.E.B. and W.L. (principal investigator)). The DCCSS-LATER is supported by the Dutch Cancer Society (DCOG2011-5027 to C.M.R., F.E.v.L. and W.T. (principal investigators) and UVA2012-5517 to C.M.R. and L.C.M.K. (principal investigators)). The FCCSS is funded by the Fondation ARC (PopHARC Grant to F.d.V. (principal investigator)), the Agence Nationale pour la Recherche Médicale (ANR, Hope-Epi Grant to F.d.V. (principal investigator)), and the Gustave Roussy Foundation (Pediatric Program ‘Guérir le Cancer de l’Enfant’ to F.d.V. (principal investigator)). 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 and KLS-5432-08-2021 to C.E.K. (principal investigator)), Kinderkrebs Schweiz ( www.kinderkrebs-schweiz.ch ) and Kinderkrebshilfe Schweiz ( www.kinderkrebshilfe.ch ). The Dutch Hodgkin Late Effects cohort has been supported by the Dutch Cancer Society (NKI 2010-4720 to F.E.v.L. (principal investigator)). Publisher Copyright: © 2023, The Author(s).
PY - 2023/9
Y1 - 2023/9
N2 - Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m−2: 1.24, 95% confidence interval (CI): 1.18–1.31), with more than twofold increased risk for survivors treated with ≥200 mg m−2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200–299 mg m−2, HR: 2.33 for 300–399 mg m−2 and HR: 2.78 for ≥400 mg m−2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59–6.63). For patients treated with or without chest irradiation, HRs per 100 mg m−2 of doxorubicin were 1.11 (95% CI: 1.02–1.21) and 1.26 (95% CI: 1.17–1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m−2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.
AB - Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m−2: 1.24, 95% confidence interval (CI): 1.18–1.31), with more than twofold increased risk for survivors treated with ≥200 mg m−2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200–299 mg m−2, HR: 2.33 for 300–399 mg m−2 and HR: 2.78 for ≥400 mg m−2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59–6.63). For patients treated with or without chest irradiation, HRs per 100 mg m−2 of doxorubicin were 1.11 (95% CI: 1.02–1.21) and 1.26 (95% CI: 1.17–1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m−2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.
UR - http://www.scopus.com/inward/record.url?scp=85170522025&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41591-023-02514-1
DO - https://doi.org/10.1038/s41591-023-02514-1
M3 - Article
C2 - 37696934
SN - 1078-8956
VL - 29
SP - 2268
EP - 2277
JO - Nature medicine
JF - Nature medicine
IS - 9
ER -