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 (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%,
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.