AACR 2015: Study Identifies a Frequent Genomic Alteration in Pleomorphic Invasive Lobular Carcinoma
Research from Rutgers Cancer Institute of New Jersey shows genomic profiling identifies 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, presented at the AACR Annual Meeting 2015, held April 18 to 22 in Philadelphia, could have therapeutic implications specific to this rare form of the disease (Abstract 4798).
Study Background
Invasive lobular carcinoma 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.
Investigators 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 anticancer 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,” said 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, which 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.
Genomic Profiling Results
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%) and three amplifications (14.3%) 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,” noted 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,” noted 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.
This study 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.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
