PHILADELPHIA –  Women with ductal carcinoma in situ (DCIS) who exhibit an overexpression of the protein HER2/neu have a six-fold increase in risk of invasive breast cancer, according to a new study from the Perelman School of Medicine. The results, published in the May issue of the journal Cancer Epidemiology, Biomarkers and Prevention, may help clinicians distinguish between DCIS that requires minimal treatment and DCIS that should be treated more aggressively.

“Not all DCIS is the same,” says Brian Czerniecki, MD, PhD, Co-Director of the Rena Rowan Breast Center at the University of Pennsylvania and Surgical Director of the Immunotherapy Program for the Abramson Cancer Center. “From a practical standpoint, if you know that a patient has a greater chance of invasive cancer when you’re doing a lumpectomy or mastectomy, then you might want to do a sentinel node biopsy, because there is a greater chance the cancer has spread to the lymph nodes.”

DCIS accounts for more than 20 percent of all breast cancer diagnoses in the United States. While many of these premalignant lesions will progress to invasive disease, clinicians currently cannot predict which women are at greatest risk.

To determine whether HER2/neu overexpression in DCIS is associated with an increased risk of invasive disease, Czerniecki’s team examined DCIS samples from 106 women diagnosed with DCIS between 2003 and 2007. Thirty seven percent of patients had DCIS that overexpressed HER2 and 21 percent of patients were found to have invasive disease after final pathology was completed. The likelihood that a woman with DCIS had invasive disease was 6.4-fold higher when her tumor overexpressed HER2 relative to women whose DCIS did not overexpress the protein, even after other known risk factors, such as DCIS size and grade, were taken into account.

Pathologists do not currently examine DCIS for HER2 expression because it does not impact treatment. However, given these new data, Czerniecki thinks it may be appropriate for clincians to change their approach in the future. The data also suggest that HER2/neu overexpression may be critical for the transition from in situ disease to invasive disease, Czerniecki says. “If HER2 is associated with invasion or plays a role in the development of invasive disease, then maybe targeting it early can keep people from moving from DCIS to invasive cancer.”

He and his colleagues are already testing anti-HER2/neu vaccines, which may help a woman’s immune system eliminate HER2-overexpressing tumor cells.

Czerniecki’s team, including Penn’s Paul J. Zhang, associate professor of Pathology and Laboratory Medicine, will publish a second paper later this year looking at the type of invasive breast cancer that develops from HER2-overexpressing DCIS. Early analysis indicates that not all of the resulting invasive tumors will remain HER2-positive, suggesting that HER2 overexpression may be an unstable phenotype but important early in the invasion process.

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PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to the National Institutes of Health, received over $366 million in NIH grants (excluding contracts) in the 2008 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center, named one of the nation’s “100 Top Hospitals” for cardiovascular care by Thomson Reuters. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, composed of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 400 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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