With a megawatt smile and adventurous spirit, Marlena Penn, 16, is a high school junior, master scuba diver, and talented underwater photographer. She has been eye-to-eye with an octopus and captured its spectacular changes in color. Evidently, her bravery and glossy, auburn curls come from her mother, Norma Roth, who is a writer, speaker, volunteer extraordinaire, and breast cancer survivor.
Put them together in an interview room, and you can feel the girl power about to burst through the door.
Even though they have a packed schedule, twice a year the pair travels from Cherry Hill, N.J., to visit The Children’s Hospital of Philadelphia as participants in the “Lessons in Epidemiology and Genetics of Adult Cancer from Youth” (LEGACY Girls Study).
Funded by the National Cancer Institute, the LEGACY study is unique in its focus on healthy, young girls and how their habits and development are related to breast health. LEGACY researchers hope to identify risk factors and lifestyle modifications that could potentially be addressed early enough to prevent or diminish the effects of cancer.
Norma and Marlena come from three generations of breast cancer. Marlena is named after her grandmother, Marlene, who died of breast cancer many years before she was born. Marlena’s grandmother had three aunts, a sister, and several cousins who also were devastated by breast cancer diagnoses. It is estimated that 5 to 10 percent of breast cancer cases result directly from gene defects — usually a mutation in the BRCA1 and BRCA2 genes — so Norma underwent genetic testing to see if she had inherited them from a parent.
Although the results were negative, she discovered in 2004 at age 40 that she indeed had breast cancer. Marlena was only 5 years old and does not remember her mom being sick, but Norma had many talks with her two other young children, now 19 and 22, to reassure them that recent breast cancer advances had made it more curable than ever before.
“We’ve seen a lot of death on both sides of my mother’s family from breast cancer, but as detection and treatment has advanced, we’ve seen better outcomes,” Norma said. “I always thought there also was some kind of environmental link. So it was interesting to me to see that the LEGACY study was tracking the health and diet of young girls to see what effects it might have on breast cancer development in the future.”
Three years ago, Norma received a study recruitment letter looking for girls to participate in LEGACY. She was hopeful that Marlena would want to join, but she left the decision up to her then 13-year-old daughter.
“I knew that from my family’s past, I might as well do it,” Marlena said. “Two visits a year is not that big of a commitment, and what I give could be really helpful to other families.”
The biggest selling point for Marlena was that bloodwork would not be performed at every visit. While she has no problems with close encounters with sharks and eels baring their sharp teeth, needlesticks make her a “hysterical mess.”
Entering its fifth year, the LEGACY study enrolled 1,040 girls ages 6 to 13 at five sites in North America. The Philadelphia site includes the University of Pennsylvania, Fox Chase Cancer Center and The Children’s Hospital of Philadelphia, where the data collection is performed. Coordinators of the Philadelphia cohort reached a milestone in 2013 when their 150th participant enrolled.
The study teams measure the girls’ growth and development, obtain either blood or saliva samples, and conduct surveys about their knowledge and perceptions of breast cancer, their health and risk behaviors, and psychosocial adjustment. The mothers also answer survey questions along the lines of, “What did you daughter eat this week?” or “Choose the picture that best illustrates your daughter’s body type.” Norma schedules their LEGACY visits to take place during school winter break and the beginning of summer, so that they do not interfere with homework or after school activities.
“The visits are easy,” Marlena said. “And it’s a nice group of people that run it. I’ve learned about how consistent everything must be in a research study. Whenever you get measured, it’s not just once, it’s five times, to make sure that everything is precise and accurate.”
Participating in the research study already has helped Marlena to think more about keeping her body healthy. Over the past few years, for example, she has answered study questions about drinking water. These raised her awareness about the importance of staying hydrated, especially when she is away on diving vacations. She is drinking only water at school this year, instead of juices, which is a big change for her.
Half the girls participating in the LEGACY study come from families with a history of breast cancer, like Marlena. They are among the first generation where women are routinely tested for genetic mutations that may increase their risk for breast cancer. Yet little research has been completed that explores how adolescents respond to learning about their familial breast cancer risk.
While none of the girls in the LEGACY study will be tested for the breast cancer genes, the researchers will assess whether genomic DNA methylation levels are modified by early-life exposures, pubertal development, and other endpoints relevant to breast cancer etiology. DNA methylation is a mechanism that cells use to switch genes on and off.
Lisa A. Schwartz, PhD, a psychologist in the Division of Oncology at CHOP, is a LEGACY co-investigator who collaborates with adult breast cancer specialists to find ways for girls from high-risk families to navigate the nuances of how growing up with knowledge of their families’ breast cancer history affects their well-being and health behaviors. She works closely with co-principal investigators Angela R. Bradbury, MD, an assistant professor of medicine in the Division of Hematology-Oncology at the Perelman School of Medicine at the University of Pennsylvania, and Mary B. Daly, MD, PhD, at Fox Chase Cancer Center.
“We want to capitalize on this window of time during the transition to adulthood when health behaviors are being solidified, and provide guidance on how they value their health and how they fit health into their identity as it’s being developed,” Dr. Schwartz said.
Communicating with her family members about their risk of breast cancer was not a difficult choice for Norma, who believes that knowledge is power and wrote a book, “Pink Ribbon Journey” that chronicles the breast cancer experiences of her family and other women of varying ages, faiths, and backgrounds.
“Way before the BRCA genes were discovered, the women in my family truly thought something in their DNA was killing them, and they felt helpless,” Norma said. “Today we have better mammograms, we have MRIs, and we have genetic testing. All of these tools are very empowering for my generation. I think the more you know, the better you can control things and change the history in your life. That’s why I really wanted Marlena to be part of the LEGACY study. It’s great, and it will be interesting to see what they do with the information in the end.”
As the LEGACY study moves into its final year, the collaborators are planning to seek additional funding to continue to follow this cohort from a biological, developmental, and behavioral standpoint.
© 2016 by The Children’s Hospital of Philadelphia Research Institute. All Rights Reserved.