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Grant Details

Grant Number: 7R01CA138819-03 Interpret this number
Primary Investigator: Daly, Mary
Organization: Research Inst Of Fox Chase Can Ctr
Project Title: LEGACY: a Cohort of Youth in Families From the Breast Cancer Family Registry
Fiscal Year: 2013
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Abstract

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.

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Publications

Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.
Authors: Pape-Zambito D, Jiang Z, Wu H, Devarajan K, Slater CM, Cai KQ, Patchefsky A, Daly MB, Chen X
Source: PLoS One, 2014;9(6), p. e100488.
EPub date: 2014 Jun 30.
PMID: 24978026
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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 IL, Buys SS, Chung WK, Frost CJ, John EM, Keegan TH, Knight JA, Terry MB, Bradbury AR
Source: J Adolesc Health, 2014 Sep;55(3), p. 352-7.
EPub date: 2014 May 17.
PMID: 24845866
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Implementation and outcomes of telephone disclosure of clinical BRCA1/2 test results.
Authors: Patrick-Miller L, Egleston BL, Daly M, Stevens E, Fetzer D, Forman A, Bealin L, Rybak C, Peterson C, Corbman M, Bradbury AR
Source: Patient Educ Couns, 2013 Dec;93(3), p. 413-9.
EPub date: 2013 Aug 19.
PMID: 24075727
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Controversies in communication of genetic screening results for cancer: a report from the American Society of Preventive Oncology's Screening Special Interest Group (ASPO's 33rd Annual Meeting, March 8 to 10, 2009, Tampa, Florida).
Authors: Patrick-Miller L, Bradbury AR, Terry MB
Source: Cancer Epidemiol Biomarkers Prev, 2010 Feb;19(2), p. 624-7.
PMID: 20142257
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Uptake and timing of bilateral prophylactic salpingo-oophorectomy among BRCA1 and BRCA2 mutation carriers.
Authors: Bradbury AR, Ibe CN, Dignam JJ, Cummings SA, Verp M, White MA, Artioli G, Dudlicek L, Olopade OI
Source: Genet Med, 2008 Mar;10(3), p. 161-6.
PMID: 18344704
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