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Wide Variety of Advanced Cancers Exhibit HER2 Gene Abnormalities

by Kathy Jones on June 4, 2013 at 10:38 PM
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 Wide Variety of Advanced Cancers Exhibit HER2 Gene Abnormalities

A study of more than 2,000 tumors has produced surprising results, but researchers hope that some of these tumors might benefit from the three anti-HER2 therapies now in clinical use.

The HER2 growth-factor gene is known to be over-active in breast and gastro-esophageal cancers.

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But now, irregularities in the genes 's expression - among them mutations, amplifications, substitutions, and translocations - have been found in 14 different advanced solid tumors.

"No one ever thought that there would be such a variety of genomic alterations in HER2 in this many solid tumors," said Massimo Cristofanilli, MD, FACP, Professor of Medical Oncology and Director of the Jefferson Breast Center at the Kimmel Cancer Center and Thomas Jefferson University Hospital.
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Dr. Cristofanilli is one of a group of co-authors from many institutions who donated tumor samples to Foundation Medicine, a cancer diagnostics company in Cambridge, Massachusetts. Foundation Medicine led and paid for the study.

He contributed about 50 metastatic breast tumor samples for the analysis, and found out that one of his patients with advanced triple negative breast cancer had a HER2 mutation.

In the study, Foundation Medicine conducted a genetic screen of more than 182 genes and 14 genetic rearrangements known to be linked to cancer in 2,223 tumor specimens. Twenty different advanced solid cancers were represented.

Researchers found HER2 alterations in 14 types of solid tumors, including 29 percent of esophageal, 20 percent of uterine, 14 percent of breast, 12 percent of stomach carcinomas, and 6 percent of all lung cancer samples.

They also found HER2 irregularities varied widely - 4.9 percent of specimens had 116 different HER2 alterations. That included 58 percent with amplifications, 25 percent with substitutions, 14 percent with indels (insertions/deletions of DNA), 2 percent with splice site variants, 2 percent with translocations, 5 percent with multiple alterations, and 2 tumors had both HER2 substitution and amplification.

Anti-HER2 therapies such as Herceptin can also treat HER2 mutations, and may also help block HER2 that is altered in the ways seen in the study, Dr. Cristofanilli said.

"This study highlights the need to study a broad range of genes at a high level of sensitivity and specificity when searching for novel targets of therapy," he noted.

"Widespread use of this approach could provide more treatment options and enable more rapid accrual to ongoing and planned trials of agents targeting pathways under study," he added.

Dr. Cristofanilli is presenting the results of the study in an oral presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

Source: ANI
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