HERSHEY, PennsylvaniaElevated levels of common serum biomarkers, including
HER2/neu, predict response to hormone therapy among women with advanced
breast cancer, according to a study reported by Kim Leitzel, MS, senior
research associate in the Experimental Oncology Research Lab, directed by Allan
Lipton, MD, at Penn State/Hershey Medical Center, Hershey, Pennsylvania.
The study was a retrospective analysis of pretreatment serum samples from
women treated with either letrozole (Femara) or tamoxifen in the pivotal trial
that found letrozole to be superior to tamoxifen as a first-line therapy for
metastatic breast cancer (J Clin Oncol 19: 2596-2606, 2001). The
researchers measured serum levels of CEA, CA 15-3, and HER2/neu and
analyzed the effects of elevated levels on clinical benefit rate and time to
The intent-to-treat patient population was 907 postmenopausal women with
metastatic breast cancer who were hormone-receptor positive or whose receptor
status was unknown. Serum was available for 548 of the women and was analyzed
with the Bayer Immuno-1 automated assay. Biomarker elevation was defined
according to commonly used cutoff points: 15 ng/mL for HER2/neu, 5 ng/mL
for CEA, and 38.5 U/mL for CA 15-3. Using these cutoff points, the percentages
of patients with elevated biomarkers were: 28% HER2/neu, 44% CEA, and
56% CA 15-3. Among patients with elevated biomarkers, 273 patients were
ultimately treated with letrozole, and 275 were treated with tamoxifen.
In univariate analysis, elevated serum CEA, CA 15-3, HER2/neu, and
number of metastatic lesions were highly significant predictors of clinical
benefit rate and time to progression. Among traditional clinical predictors,
presence of liver metastases, Karnofsky performance status, and disease-free
interval were all significant, Mr. Leitzel reported, as was treatment effect,
with letrozole being superior to tamoxifen. Factors that did not prove
predictive in univariate analysis were prior adjuvant hormonal therapy,
hormone-receptor status unknown vs positive, and patient age.
When patient response was analyzed according to serum HER2/neu
status, patients with elevated HER2/neu levels had greatly reduced
objective responses, clinical benefit rates (complete or partial response plus
stable disease for more than 24 weeks), and median time to progression.
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