Breast cancer risk in childhood cancer survivors without a history of chest radiotherapy: A report from the childhood cancer survivor study

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

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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 anthra-cycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.

Original languageEnglish (US)
Pages (from-to)910-918
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number9
DOIs
StatePublished - Mar 20 2016

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Survivors
Radiotherapy
Thorax
Breast Neoplasms
Neoplasms
Sarcoma
Leukemia
Alkylating Agents
Incidence
Gene-Environment Interaction
Anthracyclines
Drug Therapy

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Breast cancer risk in childhood cancer survivors without a history of chest radiotherapy : A report from the childhood cancer survivor study. / Henderson, Tara O.; Moskowitz, Chaya S.; Chou, Joanne F.; Bradbury, Angela R.; Neglia, Joseph Phillip; Dang, Chau T.; Onel, Kenan; Friedman, Danielle Novetsky; Bhatia, Smita; Strong, Louise C.; Stovall, Marilyn; Kenney, Lisa B.; Barnea, Dana; Lorenzi, Elena; Hammond, Sue; Leisenring, Wendy M.; Robison, Leslie L.; Armstrong, Gregory T.; Diller, Lisa R.; Oeffinger, Kevin C.

In: Journal of Clinical Oncology, Vol. 34, No. 9, 20.03.2016, p. 910-918.

Research output: Contribution to journalArticle

Henderson, TO, Moskowitz, CS, Chou, JF, Bradbury, AR, Neglia, JP, Dang, CT, Onel, K, Friedman, DN, Bhatia, S, Strong, LC, Stovall, M, Kenney, LB, Barnea, D, Lorenzi, E, Hammond, S, Leisenring, WM, Robison, LL, Armstrong, GT, Diller, LR & Oeffinger, KC 2016, 'Breast cancer risk in childhood cancer survivors without a history of chest radiotherapy: A report from the childhood cancer survivor study', Journal of Clinical Oncology, vol. 34, no. 9, pp. 910-918. https://doi.org/10.1200/JCO.2015.62.3314
Henderson, Tara O. ; Moskowitz, Chaya S. ; Chou, Joanne F. ; Bradbury, Angela R. ; Neglia, Joseph Phillip ; Dang, Chau T. ; Onel, Kenan ; Friedman, Danielle Novetsky ; Bhatia, Smita ; Strong, Louise C. ; Stovall, Marilyn ; Kenney, Lisa B. ; Barnea, Dana ; Lorenzi, Elena ; Hammond, Sue ; Leisenring, Wendy M. ; Robison, Leslie L. ; Armstrong, Gregory T. ; Diller, Lisa R. ; Oeffinger, Kevin C. / Breast cancer risk in childhood cancer survivors without a history of chest radiotherapy : A report from the childhood cancer survivor study. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 9. pp. 910-918.
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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 anthra-cycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.",
author = "Henderson, {Tara O.} and Moskowitz, {Chaya S.} and Chou, {Joanne F.} and Bradbury, {Angela R.} and Neglia, {Joseph Phillip} and Dang, {Chau T.} and Kenan Onel and Friedman, {Danielle Novetsky} and Smita Bhatia and Strong, {Louise C.} and Marilyn Stovall and Kenney, {Lisa B.} and Dana Barnea and Elena Lorenzi and Sue Hammond and Leisenring, {Wendy M.} and Robison, {Leslie L.} and Armstrong, {Gregory T.} and Diller, {Lisa R.} and Oeffinger, {Kevin C.}",
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T1 - Breast cancer risk in childhood cancer survivors without a history of chest radiotherapy

T2 - A report from the childhood cancer survivor study

AU - Henderson, Tara O.

AU - Moskowitz, Chaya S.

AU - Chou, Joanne F.

AU - Bradbury, Angela R.

AU - Neglia, Joseph Phillip

AU - Dang, Chau T.

AU - Onel, Kenan

AU - Friedman, Danielle Novetsky

AU - Bhatia, Smita

AU - Strong, Louise C.

AU - Stovall, Marilyn

AU - Kenney, Lisa B.

AU - Barnea, Dana

AU - Lorenzi, Elena

AU - Hammond, Sue

AU - Leisenring, Wendy M.

AU - Robison, Leslie L.

AU - Armstrong, Gregory T.

AU - Diller, Lisa R.

AU - Oeffinger, Kevin C.

PY - 2016/3/20

Y1 - 2016/3/20

N2 - 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 anthra-cycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.

AB - 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 anthra-cycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.

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