Studies Reveal More Clues on How Full-Term Pregnancy Protects Against Breast Cancer
At the AACR 2014 Annual Meeting in San Diego, Fox Chase scientists presented findings from three studies that examined how pregnancy reduces women’s risk of developing breast cancer.
Julia Santucci-Pereira, PhD
In the first study, Julia Santucci-Pereira, PhD, a research associate in the Breast Cancer Research Laboratory led by Jose Russo, MD, FACP, and colleagues used gene expression microarrays to compare the breast genomic profiles of cancer-free breast tissue samples from more than 100 premenopausal women — 79 parous, 30 nulliparous. They found that immune response genes are activated for a few years after pregnancy, whereas genes related to both cell differentiation and to the development of breast anatomy are permanently activated independently of the time of last pregnancy — findings that confirm pregnancy’s protective effect, as more differentiated cells are less prone to carcinogenesis.
In another study, they looked at 10 postmenopausal women using sophisticated DNA sequencing technology, and found that mothers and non-mothers displayed differences in the methylation patterns of their genes. Most of these differences occur in genes that control development — again implying differences in processes associated with the development of breast anatomy.
Finally, in a third study, Santucci-Pereira and other scientists looked deeply at differences in long non-coding RNAs in eight mothers and eight non-mothers through RNA sequencing and identified 42 non-coding RNAs with differences in expression. The researchers believe it is possible that these non-coding regions work with the genes identified in the other two studies to induce changes in the differentiation and development processes, thereby protecting women who have given birth.
The ultimate goal is to understand how these protective effects occur in order to find ways to mimic them in non-mothers — perhaps by administering compounds that target these molecular mechanisms — so that they experience the same protection against breast cancer.
Santucci-Pereira and Russo’s co-authors on the gene expression research include Eric A. Ross, PhD, Michael Slifker, MS, Suraj Peri, PhD, Ricardo López de Cicco, PhD, Yubo Zhai, BS, Irma H. Russo, MD, Theresa Nguyen, BS, and Fathima Sheriff, MD from Fox Chase, as well as researchers from New York University and Sweden’s Sunderby Hospital and Umeå University. For the other studies, they were joined by Colleen O’Malley, intern from Drexel University; Maria Barton, MSc, of Fox Chase; and researchers at the University of Texas Health Science Center.
At its annual meeting in May, the American Urological Association presented its 2014 Residents Committee Teaching Award to Robert G. Uzzo, MD, FACS, chair of surgical oncology. The award recognizes Uzzo as an outstanding urology program director who is dedicated to mentoring the next generation of urologic researchers.
Michael H. Levy, MD, PhD, vice chair of medical oncology and director of pain and palliative care, was selected by the American Society of Clinical Oncology (ASCO) for its first ever Excellence in Teaching Award. The award, presented during ASCO’s 50th Annual Meeting in Chicago in May, honors recipients for inspiring and shaping trainees’ practice of cancer medicine.
Sergei Grivennikov, PhD, assistant professor in the cancer prevention and control program, was awarded the 2014 Landon Foundation-American Association for Cancer Research INNOVATOR Award for Research in Tumor Microenvironment — a two-year, $100,000 grant — to investigate the role of cytokine IL-17-dependent inflammation in promoting tumor development.
Hormoz Ehya, MD, chief of cytopathology at Fox Chase, received the 2014 L.C. Tao Educator Award during the annual meeting of the United States and Canadian Academy of Pathology in San Diego in March. The award was presented by the Papanicolaou Society of Cytopathology.
A number of Fox Chase investigators presented research findings at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, Calif., in April.
- Medical oncologist Ranee Mehra, MD, and colleagues found that a quartet of proteins that play critical roles in cell replication, cell death, and DNA repair could lead to better targets for therapy against treatment-resistant head-and-neck squamous cell cancers by showing a correlation between the expression levels of these proteins in head and neck cancers negative for human papilloma virus (HPV). These tumors have a poorer prognosis than HPV-positive head and neck cancers. Dr. Mehra’s research could help determine potential treatments for head and neck cancers.
- Scientific assistant Shane W. O’Brien, MS, associate professor Denise C. Connolly, PhD, and colleagues shut off the spigot for two proteases that help ovarian cancer cells chew their way out of the tissue they grow in and dig in at new locations by incapacitating the activities of a protein that guides other proteins to fold into stable shapes. Building on earlier work that showed that inhibition of heat shock proteins—the protein origami helpers—limited metastases in ovarian cancer in mice, they explored how the heat shock proteins are involved in metastasis. The research could prove useful in identifying therapeutic targets that actively inhibit metastasis in patients with ovarian cancer.
- Research associate Fang Xiao, MD, PhD, and Denise C. Connolly, PhD, whose research focuses on the biological mechanisms behind metastatic epithelial ovarian cancer, found that an enzyme called focal adhesive kinase (FAK) can play a critical—and previously unstudied—role in the growth and spread of the disease. Initially, they set out to study a transcription factor called STAT3, known to be important in the proliferation and survival of cells, which led them to show that FAK inhibition results in dramatic reduction or inhibition of STAT3—a finding that suggests targeting the enzyme could be a way to also inhibit the action of STAT3 in epithelial ovarian cancer.
- Associate professor Edna Cukierman, PhD, whose research focuses on the interactions between tumors and the microenvironments where they live, found that renal, or kidney, cancer cells planted in a supportive environment proliferate with the help of an enzyme usually only seen in the brain. The enzyme may eventually become a target for cancer therapy.
- Graduate student Rashid Gabbasov, Denise C. Connolly, PhD, and fellow researchers have shown that scaffolding protein NEDD9—already known to be important in tumor invasion and spread of some lymphomas and many solid tumor types, including melanoma, neuroblastoma, and breast cancer—promotes the growth and spread of epithelial ovarian cancer. Their work shows that expression of the protein likely plays an important role both in the initial development of ovarian cancer and tumor dissemination.
Epidemiologist Presents on Head and Neck Cancer Disparities
Camille Ragin, PhD
At the sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved in Atlanta in December 2013, Fox Chase epidemiologist Camille Ragin, PhD, explored disparities in head and neck cancer. Through a systematic review and meta analysis of the related literature, Ragin provided evidence of disparities in the prevalence of HPV-positive oropharynx cancer between African Americans and U.S. whites. The focus shifted to Trinidad and Tobago in another presentation, where Ragin presented the first data on head and neck cancer trends in a Caribbean nation, and compared them with trends observed in the United States.
Fox Chase Welcomes Colleagues, Introduces New Recruits
Fox Chase President and CEO Richard I. Fisher, MD, welcomed more than 90 colleagues from around the country at a reception at the New Orleans Downtown Marriott on Saturday, December 7, 2013, during the ASH annual meeting. In his remarks, Dr. Fisher introduced both Henry C. Fung, MD, and Stefan K. Barta, MD, who are joining the Fox Chase Cancer Center team in 2014 from Chicago’s Rush University Medical Center and the Bronx’s Montefiore Medical Center respectively. Pictured from left to right are members of the Fox Chase team: Barta, Patricia L. Kropf, MD, Fisher, Fung, and Barbara Rogers, CRNP, MN, AOCN, ANP-BC.
Study Highlights the Challenge of Communicating Genetic Test Results within the Family
Mary B. Daly, MD, PhD
Since mutations in the BRCA1 and BRCA2 genes can be passed down from one generation to the next, many women who undergo testing for these genetic alterations — linked to breast and ovarian cancer risk — share the results with their relatives. But a study led by Mary B. Daly, MD, PhD, chair of the department of clinical genetics at Fox Chase, reveals that many relatives may misunderstand their family members’ test results, and less than half of those for whom testing would be considered appropriate plan to get tested themselves. Daly presented the study results in December at the 2013 SABCS.
Daly and her team surveyed relatives of people who had undergone genetic testing and who said they had shared their results with their family. More than one quarter of those surveyed reported the test results incorrectly. Relatives were most likely to understand positive and true negative results, while only 60 percent understood “indeterminate” or uncertain results.
Only about half (52 percent) of those whose relative tested positive for the BRCA1/2 genes said they planned to get tested themselves. Among those whose relative tested negative but who knew the gene was present in their families, only 36 percent said they were going to find out their own genetic risk.
As part of the study, half of the people getting tested were asked to participate in coaching sessions to help them communicate their results to relatives, but the sessions proved no more effective than educational sessions about overall health. Daly now plans to explore the effect of reaching out directly to the relatives of someone who has undergone genetic testing (with that person’s permission), to see if hearing the results from an expert helps family members understand what they mean.
Daly’s co-authors include Susan Montgomery, RN, BSN, OCN, Ruth Bingler, BS, and Karen Ruth, MS.