A Frequent Genomic Alteration is Identified in a Rare Subset of Breast Cancer

Research from Rutgers Cancer Institute of New Jersey presented at national meeting

Kim Hirshfield, MD, PhDNew Brunswick, N.J. – Research from Rutgers Cancer Institute of New Jersey shows genomic profiling identifies genomic mutations in a gene associated with a rare subset of breast cancer – mutations that cannot otherwise be identified with standard clinical analysis of cells and tissue. The findings, being presented as part of a poster presentation at the Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia this week, could have therapeutic implications specific to this rare form of the disease, say the authors. 

Invasive lobular carcinoma is a cancer that starts in the lobules, an area of the breast where milk is produced. It is normally very sensitive to estrogen-targeting therapies because of high expression of the estrogen receptor protein, but rarely shows high expression of the HER2 protein. Pleomorphic invasive lobular carcinoma is a unique subset of lobular breast cancer that has abnormally aggressive tumor cells and results in poorer outcomes than the classic lobular breast cancer. Recently, alterations were found in the ERBB2 gene in lobular breast cancers that recur after initial treatment. The ERBB2 gene directs the cancer cell to make the HER2 protein which is routinely tested for using standard pathologic techniques.

As part of the precision medicine initiative at the Cancer Institute of New Jersey, investigators – which include colleagues from Rutgers Robert Wood Johnson Medical School and RUCDR Infinite Biologics, the world’s largest university-based biorepository, located within the Human Genetics Institute of New Jersey – wanted to define the relationship of ERBB2 alterations in the pleomorphic form of the disease.

“Figuring out specific differences that are not visible under the microscope allows us to intervene with more appropriate and potentially life-saving therapy. With genomic sequencing detecting ERBB2 alterations in this form of cancer, we have an opportunity to identify anti-cancer therapies that would specifically target that abnormality and that would otherwise not be given to those patients who could benefit. These genomic abnormalities would be overlooked with current, standard of care laboratory testing for breast cancer,” says lead author Kim M. Hirshfield, MD, PhD, breast medical oncologist at the Cancer Institute and assistant professor of medicine at Rutgers Robert Wood Johnson Medical School.

Utilizing the invasive breast cancer data set of 962 cases in The Cancer Genome Atlas, all breast cancers with alterations in the CDH1 gene (that gives instructions to make a protein that causes cancer cells to stick to one another and defines lobular breast cancers) were identified. Tumors were evaluated by a pathologist at the microscopic level to classify them as either classic or pleomorphic lobular breast cancer. Independent identification of ERBB2 gene alterations was completed and frequency of that alteration, as well as others in the PTEN, PIK3CA and TP53 genes, were determined. An additional 16 cases from the Cancer Institute were evaluated using an advanced form of tumor DNA sequencing at RUCDR.

Of 116 eligible breast cancers from The Cancer Genome Atlas, 86 were invasive lobular breast cancer. Of that number, 21 cases were found to be the pleomorphic type. Nine ERBB2 mutations (42.9 percent) and three amplifications (14.3 percent) were found in the pleomorphic type and none were found in the classic type. There were no significant differences in the frequency of the other gene alterations examined between the two types of cancer. With that, investigators say the alterations in the ERBB2 gene strongly associate with pleomorphic lobular breast cancer but not the classic form of the disease. Data from the additional 16 cases from the Cancer Institute validate the findings observed on breast cancers from The Cancer Genome Atlas. 

“In identifying a specific abnormality in a patient’s cancer instead of the overall organ where it first presented, the opportunity exists to provide tailored therapies for patients,” notes Lorna Rodriguez, MD, PhD, director of the precision medicine initiative at the Cancer Institute and professor of obstetrics, gynecology and reproductive sciences at Robert Wood Johnson Medical School. “Advances in genomic sequencing are helping clinicians go beyond a ‘one size fits all’ approach for treatment.”

“Along with helping to guide the use of existing treatments, such findings can also aid in developing the next generation of therapies through clinical trials. It is our aim at Rutgers Cancer Institute of New Jersey to build upon this work,” notes senior author of the work, Shridar Ganesan, MD, PhD, associate director for translational science at the Cancer Institute and associate professor of medicine and pharmacology at Robert Wood Johnson Medical School.

Along with Drs. Hirshfield, Rodriguez and Ganesan, authors include Renee Arlow, Heather K. Feld and Nicola Barnard, all Robert Wood Johnson Medical School; Li Liang, Rutgers University; Hua Zhong and Gyan Bhanot, Cancer Institute; and Amrik S. Sahota and Andrew Brooks, Rutgers University.

The work was supported in part by the Jattrude Fogarty Trust and the Val Skinner Foundation. The overall precision medicine initiative at the Cancer Institute is supported in part by a $10 million anonymous gift.   

About Rutgers Cancer Institute of New Jersey
Rutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, the Cancer Institute of New Jersey is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention. Physician-scientists at the Cancer Institute engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life.  To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 848-932-3637 or visit www.cinj.org/giving. Follow us on Facebook at www.facebook.com/TheCINJ.

The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides the highest quality cancer care and rapid dissemination of important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. System Partner: Meridian Health (Jersey Shore University Medical Center, Ocean Medical Center, Riverview Medical Center, Southern Ocean Medical Center, and Bayshore Community Hospital). Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Medical Center and Carol G. Simon Cancer Center at Overlook Medical Center. Affiliate Hospitals: JFK Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), and Robert Wood Johnson University Hospital Somerset. 

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