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Multicenter Study
. 2016 Mar 20;34(9):910-8.
doi: 10.1200/JCO.2015.62.3314. Epub 2015 Dec 23.

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

Tara O Henderson  1 , Chaya S Moskowitz  2 , Joanne F Chou  2 , Angela R Bradbury  2 , Joseph Phillip Neglia  2 , Chau T Dang  2 , Kenan Onel  2 , Danielle Novetsky Friedman  2 , Smita Bhatia  2 , Louise C Strong  2 , Marilyn Stovall  2 , Lisa B Kenney  2 , Dana Barnea  2 , Elena Lorenzi  2 , Sue Hammond  2 , Wendy M Leisenring  2 , Leslie L Robison  2 , Gregory T Armstrong  2 , Lisa R Diller  2 , Kevin C Oeffinger  2
Affiliations
Multicenter Study

Breast Cancer Risk in Childhood Cancer Survivors Without a History of Chest Radiotherapy: A Report From the Childhood Cancer Survivor Study

Tara O Henderson et al. J Clin Oncol. .

Abstract

Purpose: Little is known about the breast cancer risk among childhood cancer survivors who did not receive chest radiotherapy. We sought to determine the magnitude of risk and associated risk factors for breast cancer among these women.

Patients and methods: We evaluated cumulative breast cancer risk in 3,768 female childhood cancer survivors without a history of chest radiotherapy who were participants in the Childhood Cancer Survivor Study.

Results: With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. A four-fold increased breast cancer risk (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3) was observed when compared with the general population. Risk was highest among sarcoma and leukemia survivors (SIR = 5.3; 95% CI, 3.6 to 7.8 and SIR = 4.1; 95% CI, 2.4 to 6.9, respectively). By the age of 45 years, the cumulative incidence of breast cancer in sarcoma and leukemia survivors was 5.8% (95% CI, 3.7 to 8.4) and 6.3% (95% CI, 3.0 to 11.3), respectively. No other primary cancer diagnosis was associated with an elevated risk. Alkylators and anthracyclines were associated with an increased breast cancer risk in a dose-dependent manner (P values from test for trend were both < .01).

Conclusions: Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Study flow diagram. (*) Dataset used for all analyses involving treatment data.
Fig 2.
Fig 2.
(A) Cumulative incidence of breast cancer in childhood cancer survivors without a history of chest radiotherapy. (B) Cumulative incidence of breast cancer in childhood sarcoma and leukemia survivors without a history of chest radiotherapy.
See this image and copyright information in PMC

Comment in

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