Grant Number:	5R01CA138844-05 Interpret this number
Primary Investigator:	Andrulis, Irene
Organization:	Sinai Health System
Project Title:	LEGACY: a Cohort of Youth in Families From the Breast Cancer Family Registry
Fiscal Year:	2015

DESCRIPTION (provided by applicant): The identification of risk factors for breast cancer has tremendous clinical importance. One of the strongest risk factors is a family history of breast cancer. Most studies have focused on genetics and lifestyle factors in adult women. However, there is growing evidence that young girls may be particularly sensitive to exposures that either initiate or protect against breast cancer. These include ionizing radiation exposure, childhood and adolescent growth, body composition, and physical activity. It remains unknown whether effects of early life and childhood exposures are greater in individuals with a family history of breast cancer (BCFH). Studies on individuals with a family history of cancer have been of great value in the identification of genetic alterations that play a role in cancer, not only in the familial setting, but more generally in sporadic cancer as well; similarly, familial clustering is also likely associated with clustering of risk factors influenced by both genes and environment, as well as clustering of health-related behaviors, and may therefore be a powerful setting in which to identify factors important in both familial and sporadic breast cancer. We propose to establish a cohort of 450 girls aged 6-13 years who are the offspring of women enrolled in the Breast Cancer Family Registry (BCFR), and 450 girls from families without breast cancer. The youth cohort, named LEGACY (Lessons in Epidemiology and Genetics of Adult Cancer from Youth), will be followed prospectively, with repeated data and biospecimen collection at 6-month intervals. The objectives are to 1) study prospectively the association of pubertal development (onset and tempo of breast development), age at menarche, and breast tissue characteristics over time with childhood measures of body size, growth, lifestyle factors (physical activity, diet, vitamin D), built environment, and selected biomarkers of exposure, and to assess whether these associations are modified by BCFH; 2) assess the association of childhood exposures with genomic DNA methylation and changes in genomic DNA methylation, and assess whether genomic DNA methylation levels are modified by BCFH; and 3) evaluate longitudinally how psychosocial adjustment and behaviors of girls from breast cancer families differ from those of girls from families without breast cancer. Unlike any other youth cohort, the LEGACY cohort is unique in that it will be enriched with girls at increased breast cancer risk, given their family history, and covering a wide spectrum of risk. It is currently not known how young girls at increased risk can lower their risk, how they adapt to their familial risk, and how such familial risk impacts their behaviors throughout development. Understanding these relations is necessary for the successful translation of early-life exposure information into health-promoting and breast cancer-preventing behaviors during childhood and adolescence. LEGACY will provide a rich resource for molecular and biomarker studies in young girls that will inform our understanding of when breast cancer susceptibility begins, whether it is influenced by modifiable determinants, and how it impacts psychosocial adjustment and behaviors. PUBLIC HEALTH RELEVANCE: Focusing on childhood and adolescence is particularly important for developing breast cancer prevention programs as we know that the interplay of modifiable factors such as nutrition, body size, and physical activity is apparent early in life, and that early life patterns have long lasting influence on adult patterns. Knowledge gained from the proposed study will not only be relevant for breast cancer prevention strategies for individuals with a family history of breast cancer families, but also for individuals without a family history. A thorough understanding of perceptions of risk and risk reduction interventions among children and adolescents is critical for the implementation of effective prevention programs that start early in life.




Maternal and prenatal factors and age at thelarche in the LEGACY Girls Study cohort: implications for breast cancer risk.
Authors: Goldberg M. , McDonald J.A. , Houghton L.C. , Andrulis I.L. , Knight J.A. , Bradbury A.R. , Schwartz L.A. , Buys S.S. , Frost C.J. , Daly M.B. , et al. .
Source: International journal of epidemiology, 2023-02-08; 52(1), p. 272-283.
PMID: 35613015
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Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk.
Authors: Jennings C. , Wynn J. , Miguel C. , Levinson E. , Florido M.E. , White M. , Sands C.B. , Schwartz L.A. , Daly M. , O'Toole K. , et al. .
Source: The Journal of pediatrics, 2022 Dec; 251, p. 113-119.e7.
EPub date: 2022-06-29.
PMID: 35777474
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Body mass index rebound and pubertal timing in girls with and without a family history of breast cancer: the LEGACY girls study.
Authors: Houghton L.C. , Wei Y. , Wang T. , Goldberg M. , Paniagua-Avila A. , Sweeden R.L. , Bradbury A. , Daly M. , Schwartz L.A. , Keegan T. , et al. .
Source: International journal of epidemiology, 2022-10-13; 51(5), p. 1546-1555.
PMID: 35157067
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Common Childhood Viruses and Pubertal Timing: The LEGACY Girls Study.
Authors: McDonald J.A. , Cherubin S. , Goldberg M. , Wei Y. , Chung W.K. , Schwartz L.A. , Knight J.A. , Schooling C.M. , Santella R.M. , Bradbury A.R. , et al. .
Source: American journal of epidemiology, 2021-05-04; 190(5), p. 766-778.
PMID: 33128063
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Prepubertal Internalizing Symptoms and Timing of Puberty Onset in Girls.
Authors: Knight J.A. , Kehm R.D. , Schwartz L. , Frost C.J. , Chung W.K. , Colonna S. , Keegan T.H.M. , Goldberg M. , Houghton L.C. , Hanna D. , et al. .
Source: American journal of epidemiology, 2021-02-01; 190(3), p. 431-438.
PMID: 33057572
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Comparison of methods to assess onset of breast development in the LEGACY Girls Study: methodological considerations for studies of breast cancer.
Authors: Houghton L.C. , Knight J.A. , De Souza M.J. , Goldberg M. , White M.L. , O'Toole K. , Chung W.K. , Bradbury A.R. , Daly M.B. , Andrulis I.L. , et al. .
Source: Breast cancer research : BCR, 2018-04-18; 20(1), p. 33.
EPub date: 2018-04-18.
PMID: 29669587
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Breast cancer family history and allele-specific DNA methylation in the legacy girls study.
Authors: Wu H.C. , Do C. , Andrulis I.L. , John E.M. , Daly M.B. , Buys S.S. , Chung W.K. , Knight J.A. , Bradbury A.R. , Keegan T.H.M. , et al. .
Source: Epigenetics, 2018; 13(3), p. 240-250.
EPub date: 2018-04-02.
PMID: 29436922
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Pubertal development in girls by breast cancer family history: the LEGACY girls cohort.
Authors: Terry M.B. , Keegan T.H.M. , Houghton L.C. , Goldberg M. , Andrulis I.L. , Daly M.B. , Buys S.S. , Wei Y. , Whittemore A.S. , Protacio A. , et al. .
Source: Breast cancer research : BCR, 2017-06-08; 19(1), p. 69.
EPub date: 2017-06-08.
PMID: 28595647
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Non-invasive optical spectroscopic monitoring of breast development during puberty.
Authors: Lilge L. , Terry M.B. , Walter J. , Pinnaduwage D. , Glendon G. , Hanna D. , Tammemagi M.L. , Bradbury A. , Buys S. , Daly M. , et al. .
Source: Breast cancer research : BCR, 2017-02-06; 19(1), p. 12.
EPub date: 2017-02-06.
PMID: 28166807
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Comparison of Clinical, Maternal, and Self Pubertal Assessments: Implications for Health Studies.
Authors: Terry M.B. , Goldberg M. , Schechter S. , Houghton L.C. , White M.L. , O'Toole K. , Chung W.K. , Daly M.B. , Keegan T.H. , Andrulis I.L. , et al. .
Source: Pediatrics, 2016 Jul; 138(1), .
EPub date: 2016-06-08.
PMID: 27279647
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The LEGACY Girls Study: Growth and Development in the Context of Breast Cancer Family History.
Authors: John E.M. , Terry M.B. , Keegan T.H. , Bradbury A.R. , Knight J.A. , Chung W.K. , Frost C.J. , Lilge L. , Patrick-Miller L. , Schwartz L.A. , et al. .
Source: Epidemiology (Cambridge, Mass.), 2016 May; 27(3), p. 438-48.
PMID: 26829160
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Psychosocial Adjustment in School-age Girls With a Family History of Breast Cancer.
Authors: Bradbury A.R. , Patrick-Miller L. , Schwartz L. , Egleston B. , Sands C.B. , Chung W.K. , Glendon G. , McDonald J.A. , Moore C. , Rauch P. , et al. .
Source: Pediatrics, 2015 Nov; 136(5), p. 927-37.
EPub date: 2015-10-19.
PMID: 26482668
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Human subjects protection: an event monitoring committee for research studies of girls from breast cancer families.
Authors: Harris D. , Patrick-Miller L. , Schwartz L. , Lantos J. , Daugherty C. , Daly M. , Andrulis I.L. , Buys S.S. , Chung W.K. , Frost C.J. , et al. .
Source: The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 2014 Sep; 55(3), p. 352-7.
EPub date: 2014-05-17.
PMID: 24845866
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Global DNA methylation levels in girls with and without a family history of breast cancer.
Authors: Wu H.C. , John E.M. , Ferris J.S. , Keegan T.H. , Chung W.K. , Andrulis I. , Delgado-Cruzata L. , Kappil M. , Gonzalez K. , Santella R.M. , et al. .
Source: Epigenetics, 2011 Jan; 6(1), p. 29-33.
EPub date: 2011-01-01.
PMID: 20930546
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