Grant Number:	5R01CA136783-04 Interpret this number
Primary Investigator:	Moskowitz, Chaya
Organization:	Sloan-Kettering Inst Can Research
Project Title:	Prediction Model: Breast Cancer in Women Irradiated for a Pediatric Malignancy
Fiscal Year:	2013

DESCRIPTION (provided by applicant): Survivors of a pediatric malignancy are at risk for serious long-term morbidity and premature mortality related to their treatment. Women who were treated with chest radiation for their childhood cancer have an increased risk of developing breast cancer at a young age. We use the term chest radiation to refer to radiation that includes the following fields: mantle, mediastinal, lung, total body irradiation, or spinal. Models for predicting the absolute risk of breast cancer, such as the well-known Gail model, have been used extensively to advise patients on their individual risk of developing breast cancer and to design prevention trials. The majority of these risk calculators are not immediately applicable to survivors of a previous malignancy who have a risk that is modified by previous treatments. Moreover, there is conflicting evidence as to whether various non-treatment related factors, including the traditional breast cancer risk factors, are associated with the risk of breast cancer in these women. The traditional risk factors include age, age at menarche, age at birth of first live child, number of first-degree relatives with breast cancer, number of previous breast biopsies, and history of atypical hyperplasia. We propose to utilize the unique resources of the North American Childhood Cancer Survivor Study (CCSS) and the Dutch LATe Effect Registry (LATER) cohorts. Our first aim is to develop a risk prediction model that integrates chest radiation dose and volume, treatment-related exposures, the traditional risk factors, and other possible risk factors such as age at menopause, body mass index, the number of years with intact ovarian function after radiotherapy, and use of hormone replacement or oral contraceptive therapy, in order to estimate the individualized absolute risk of breast cancer for women who were treated with chest radiation for a childhood cancer. The model will be developed using the original CCSS cohort in which there are 1,677 female participants who were treated with chest radiation and would be included in this analysis. Of these 1,677 women, 187 women had developed breast cancer by the time of this application. Our second aim is to validate the prediction model on independent data. The validation cohort will consist of about 1225 female participants in the expanded CCSS cohort and 1087 female participants in the Dutch LATER cohort. We estimate that approximately 100 of these women will have breast cancer. The third aim is to create and disseminate a risk calculator that provides computer-assisted risk prediction. Our objective is to present a tool in an easily accessible format and disseminate it for clinical use by physicians and patients. The long-term goals of this project are to provide a means for facilitating conversations between physicians and their patients about appropriate screening and preventive strategies and to help refine screening recommendations for this population.




Association of Changes in Cancer Therapy Over 3 Decades With Risk of Subsequent Breast Cancer Among Female Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study (CCSS).
Authors: Henderson T.O. , Liu Q. , Turcotte L.M. , Neglia J.P. , Leisenring W. , Hodgson D. , Diller L. , Kenney L. , Morton L. , Berrington de Gonzalez A. , et al. .
Source: Jama Oncology, 2022-10-13 00:00:00.0; , .
EPub date: 2022-10-13 00:00:00.0.
PMID: 36227603
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Development and Validation of a Breast Cancer Risk Prediction Model for Childhood Cancer Survivors Treated With Chest Radiation: A Report From the Childhood Cancer Survivor Study and the Dutch Hodgkin Late Effects and LATER Cohorts.
Authors: Moskowitz C.S. , Ronckers C.M. , Chou J.F. , Smith S.A. , Friedman D.N. , Barnea D. , Kok J.L. , de Vries S. , Wolden S.L. , Henderson T.O. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2021-09-20 00:00:00.0; 39(27), p. 3012-3021.
EPub date: 2021-05-28 00:00:00.0.
PMID: 34048292
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Updated Breast Cancer Surveillance Recommendations for Female Survivors of Childhood, Adolescent, and Young Adult Cancer From the International Guideline Harmonization Group.
Authors: Mulder R.L. , Hudson M.M. , Bhatia S. , Landier W. , Levitt G. , Constine L.S. , Wallace W.H. , van Leeuwen F.E. , Ronckers C.M. , Henderson T.O. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2020-12-10 00:00:00.0; 38(35), p. 4194-4207.
EPub date: 2020-09-29 00:00:00.0.
PMID: 33078972
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Association of Breast Cancer Risk After Childhood Cancer With Radiation Dose to the Breast and Anthracycline Use: A Report From the Childhood Cancer Survivor Study.
Authors: Veiga L.H. , Curtis R.E. , Morton L.M. , Withrow D.R. , Howell R.M. , Smith S.A. , Weathers R.E. , Oeffinger K.C. , Moskowitz C.S. , Henderson T.O. , et al. .
Source: Jama Pediatrics, 2019-10-28 00:00:00.0; , .
EPub date: 2019-10-28 00:00:00.0.
PMID: 31657853
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Promoting Breast Cancer Surveillance: The EMPOWER Study, a Randomized Clinical Trial in the Childhood Cancer Survivor Study.
Authors: Oeffinger K.C. , Ford J.S. , Moskowitz C.S. , Chou J.F. , Henderson T.O. , Hudson M.M. , Diller L. , McDonald A. , Ford J. , Mubdi N.Z. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2019-08-20 00:00:00.0; 37(24), p. 2131-2140.
EPub date: 2019-07-01 00:00:00.0.
PMID: 31260642
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Mortality After Breast Cancer Among Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.
Authors: Moskowitz C.S. , Chou J.F. , Neglia J.P. , Partridge A.H. , Howell R.M. , Diller L.R. , Novetsky Friedman D. , Barnea D. , Morton L.M. , Turcotte L.M. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2019-08-20 00:00:00.0; 37(24), p. 2120-2130.
EPub date: 2019-07-01 00:00:00.0.
PMID: 31260644
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Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study.
Authors: Moskowitz C.S. , Chou J.F. , Sklar C.A. , Barnea D. , Ronckers C.M. , Friedman D.N. , Neglia J.P. , Turcotte L. , Howell R.M. , Henderson T.O. , et al. .
Source: British Journal Of Cancer, 2017-07-11 00:00:00.0; 117(2), p. 290-299.
EPub date: 2017-06-20 00:00:00.0.
PMID: 28632729
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Inference for the difference in the area under the ROC curve derived from nested binary regression models.
Authors: Heller G. , Seshan V.E. , Moskowitz C.S. , Gönen M. .
Source: Biostatistics (oxford, England), 2017-04-01 00:00:00.0; 18(2), p. 260-274.
PMID: 27655817
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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
Authors: Henderson T.O. , Moskowitz C.S. , Chou J.F. , Bradbury A.R. , Neglia J.P. , Dang C.T. , Onel K. , Novetsky Friedman D. , Bhatia S. , Strong L.C. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2016-03-20 00:00:00.0; 34(9), p. 910-8.
PMID: 26700127
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Health care utilization, lifestyle, and emotional factors and mammography practices in the Childhood Cancer Survivor Study.
Authors: Rosenberg S.M. , Moskowitz C.S. , Ford J.S. , Henderson T.O. , Frazier A.L. , Diller L.R. , Hudson M.M. , Stanton A.L. , Chou J.F. , Smith S. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Nov; 24(11), p. 1699-706.
PMID: 26304504
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Breast Cancer Following Spinal Irradiation For A Childhood Cancer: A Report From The Childhood Cancer Survivor Study
Authors: Moskowitz C.S. , Malhotra J. , Chou J.F. , Wolden S.L. , Weathers R.E. , Stovall M. , Armstrong G.T. , Leisenring W.M. , Neglia J.P. , Robison L.L. , et al. .
Source: Radiotherapy And Oncology : Journal Of The European Society For Therapeutic Radiology And Oncology, 2015 Nov; 117(2), p. 213-6.
PMID: 26391961
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Predicting Adverse Health Outcomes In Long-term Survivors Of A Childhood Cancer
Authors: Moskowitz C.S. , Oeffinger K.C. .
Source: Children (basel, Switzerland), 2014 Sep; 1(2), p. 63-73.
PMID: 26236650
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Breast cancer after chest radiation therapy for childhood cancer.
Authors: Moskowitz C.S. , Chou J.F. , Wolden S.L. , Bernstein J.L. , Malhotra J. , Novetsky Friedman D. , Mubdi N.Z. , Leisenring W.M. , Stovall M. , Hammond S. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2014-07-20 00:00:00.0; 32(21), p. 2217-23.
EPub date: 2014-07-20 00:00:00.0.
PMID: 24752044
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Solid Tumor Second Primary Neoplasms: Who Is At Risk, What Can We Do?
Authors: Oeffinger K.C. , Baxi S.S. , Novetsky Friedman D. , Moskowitz C.S. .
Source: Seminars In Oncology, 2013 Dec; 40(6), p. 676-89.
PMID: 24331190
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Testing the incremental predictive accuracy of new markers.
Authors: Begg C.B. , Gonen M. , Seshan V.E. .
Source: Clinical Trials (london, England), 2013 Oct; 10(5), p. 690-2.
PMID: 23881367
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Comparing ROC curves derived from regression models.
Authors: Seshan V.E. , Gönen M. , Begg C.B. .
Source: Statistics In Medicine, 2013-04-30 00:00:00.0; 32(9), p. 1483-93.
EPub date: 2013-04-30 00:00:00.0.
PMID: 23034816
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One Statistical Test Is Sufficient For Assessing New Predictive Markers
Authors: Vickers,A.J. , Cronin,A.M. , Begg,C.B. .
Source: Bmc Medical Research Methodology, 2011; 11, p. 13.
PMID: 21276237
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