SAN ANTONIOA retrospective study presented at the 24th Annual San Antonio Breast Cancer Symposium (abstract 18) has shown that breast cancer patients selected for treatment with trastuzumab(Drug information on trastuzumab) (Herceptin) combination therapy on the basis of HER-2 gene amplification by fluorescent in situ hybridization (FISH) may have improved clinical benefits.
"I think the data really point toward changing our approach to detection with FISH," said the study’s lead author Robert D. Mass, MD, associate director of oncology, Genentech, Inc.
It has been nearly 15 years since Slamon and his colleagues described the characteristic molecular alteration that leads to overamplification of HER-2. This work led to the pivotal trial of trastuzu-mab plus chemotherapy vs chemotherapy alone as first-line treatment of metastatic breast cancer, which demonstrated an improved response rate with trastuzumab: 50% vs 32%, respectively.
To qualify for enrollment, patients had to overexpress HER-2 at the 2+ or 3+ level. The investigators used a standardized, semiquantitative immunohistochemistry (IHC) assay to screen for enrollment. A previous analysis demonstrated HER-2 amplification in 89% of 3+ tumors and in 24% of 2+ tumors.
"Since trastuzumab was approved some 3 years ago to treat advanced breast cancer, we have come to realize that IHC as a detection method has some significant accuracy issues. These issues led us to evaluate a more precise and accurate way to measure overexpression," Dr. Mass said.
He explained that FISH technology has a built-in control mechanism that prevents some of the false-negatives that occur with use of IHC.