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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA138819-04
Application #
8607512
Study Section
Special Emphasis Panel (ZRG1-PSE-K (60))
Program Officer
Seminara, Daniela
Project Start
2011-03-10
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
4
Fiscal Year
2014
Total Cost
$667,309
Indirect Cost
$152,685
Name
Research Institute of Fox Chase Cancer Center
Department
Type
DUNS #
064367329
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Terry, Mary Beth; Keegan, Theresa H M; Houghton, Lauren C et al. (2017) Pubertal development in girls by breast cancer family history: the LEGACY girls cohort. Breast Cancer Res 19:69
Lilge, Lothar; Terry, Mary Beth; Walter, Jane et al. (2017) Non-invasive optical spectroscopic monitoring of breast development during puberty. Breast Cancer Res 19:12
Bradbury, Angela R; Patrick-Miller, Linda; Schwartz, Lisa A et al. (2016) Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History. J Clin Oncol 34:3409-16
Terry, Mary Beth; Goldberg, Mandy; Schechter, Sarah et al. (2016) Comparison of Clinical, Maternal, and Self Pubertal Assessments: Implications for Health Studies. Pediatrics 138:
John, Esther M; Terry, Mary Beth; Keegan, Theresa H M et al. (2016) The LEGACY Girls Study: Growth and Development in the Context of Breast Cancer Family History. Epidemiology 27:438-48
Bradbury, Angela R; Patrick-Miller, Linda; Schwartz, Lisa et al. (2015) Psychosocial Adjustment in School-age Girls With a Family History of Breast Cancer. Pediatrics 136:927-37
Wu, Hui-Chen; Wang, Qiao; Chung, Wendy K et al. (2014) Correlation of DNA methylation levels in blood and saliva DNA in young girls of the LEGACY Girls study. Epigenetics 9:929-33
Pape-Zambito, Dana; Jiang, Zhengyu; Wu, Hong et al. (2014) Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients. PLoS One 9:e100488
Harris, Diana; Patrick-Miller, Linda; Schwartz, Lisa et al. (2014) Human subjects protection: an event monitoring committee for research studies of girls from breast cancer families. J Adolesc Health 55:352-7
Patrick-Miller, Linda; Egleston, Brian L; Daly, Mary et al. (2013) Implementation and outcomes of telephone disclosure of clinical BRCA1/2 test results. Patient Educ Couns 93:413-9

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