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The LEGACY Girls Study

Growth and Development in the Context of Breast Cancer Family History

John, Esther M.; Terry, Mary Beth; Keegan, Theresa H. M.; Bradbury, Angela R.; Knight, Julia A.; Chung, Wendy K.; Frost, Caren J.; Lilge, Lothar; Patrick-Miller, Linda; Schwartz, Lisa A.; Whittemore, Alice S.; Buys, Saundra S.; Daly, Mary B.; Andrulis, Irene L.

doi: 10.1097/EDE.0000000000000456
Anthropometry
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Background: Although the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls’ development include girls at increased breast cancer risk due to their family history.

Methods: The Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6–13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy.

Results: During this initial 5-year phase of the study, follow-up visits are conducted every 6 months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were premenarcheal and 49% were at breast Tanner stage T1.

Conclusions: This study design allows thorough examination of events affecting girls’ growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease.

From the aCancer Prevention Institute of California, Fremont, CA; bDepartment of Health Research & Policy (Epidemiology), and Stanford Cancer Institute, Stanford School of Medicine, Stanford, CA; cDepartment of Epidemiology, Columbia University Mailman School of Public Health, New York, NY; dHerbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY; eDepartments of Medicine and Medical Ethics & Health Policy, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA; fLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; gDivision of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; hDepartments of Pediatrics and Medicine, Columbia University, New York, NY; iCollege of Social Work, University of Utah, Salt Lake City, UT; jPrincess Margaret Cancer Centre, Toronto, ON, Canada; kCenter for Clinical Cancer Genetics and Department of Medicine, University of Chicago, Chicago, IL; lThe Children’s Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA; mDepartment of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT; nDepartment of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA; and oDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Submitted 23 March 2015; accepted 28 January 2016.

Supported by the National Cancer Institute at the National Institutes of Health (Grants CA138638 to E. M. John, CA138819 to M. B. Daly and A. R. Bradbury, CA138822 to M. B. Terry, and CA138844 to I. L. Andrulis) and the Canadian Breast Cancer Foundation (I. L. Andrulis). The work at the New York site was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. I. L. Andrulis holds the Anne and Max Tanenbaum Chair in Molecular Medicine at Mount Sinai Hospital and the University of Toronto.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Correspondence: Esther M. John, Cancer Prevention Institute of California, 2201 Walnut Ave, Suite 300, Fremont, CA 94538. E-mail: Esther.John@cpic.org.

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