Baseline serum extracellular domain HER2 expression in hormone receptor-positive metastatic breast cancer: correlation with known tissue HER2 status.
Authors: S Johnston, L O'Rouke, W Wang, M Pegram, MF Press, J Maltzman
Journal: Cancer Research (2009)

Abstract Abstract #3147 Background: The extracellular domain (ECD) of the HER2 protein is cleaved by metalloproteases and shed into the serum. Serum ECD (sECD) HER2 can be detected by ELISA and may have prognostic/predictive associations in patients (pts) with breast cancer. Although use of sECD HER2 as a surrogate for HER2 overexpression in hormone receptor-positive (HR+) metastatic breast cancer (MBC) is controversial, seroconversion can occur at disease relapse and may reflect a change in tumor HER2 status that is associated with a poorer prognosis. EGF30008 is a double-blind, placebo-controlled, first-line, phase III trial of letrozole with/without lapatinib in 1,286 postmenopausal women with HR+ MBC. We report baseline sECD HER2 at study entry on all pts and the association with original tumor HER2 status.&amp;#x2028; Methods: Serum samples were collected at study entry and every 4 weeks on study, including at disease progression. Patients were defined as sECD HER2+ if baseline sECD HER2 was ≥15 ng/mL. HER2 status was evaluated in tumor tissue by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), using conventional cutoffs. To assess the correlation between baseline sECD HER2 and tumor tissue HER2 status, odds ratios (OR) with 95% confidence intervals (CI) and sensitivity/specificity (tumor tissue HER2 status as standard) were calculated. Data were from a blinded cutoff on 12May08. These analyses will be repeated after the database is finalized and unblinded.&amp;#x2028; Results: Mean age was 63 ± 9.8 years. All pts had a HR+ original tumor, and 217 (17%) pts were confirmed as HER2+ by IHC or FISH. Median time from primary diagnosis to MBC was&amp;#x2028; 3.3 years (range 0 - 33.9 yrs). Baseline sECD HER2 levels ranged from 2.5 to &amp;gt; 560 ng/mL (mean 21 ± 60 ng/mL) with a bimodal distribution consistent with previously published data. The mean was 62 ng/mL (range 2.8 to &amp;gt; 560 ng/mL) for HER2+ pts and 12 ng/mL (range 2.5 to 113.1 ng/mL) for HER2-negative pts. The OR between sECD HER2 at study entry and HER2 status of the original tumor was 4.5 (95% CI: 3.2, 6.2) with 42% sensitivity and 86% specificity.&amp;#x2028; Conclusions: This OR suggests some correlation exists between baseline sECD HER2 and original tumor HER2 status. We cannot assess the rate of seroconversion that may have occurred from primary diagnosis until MBC at study entry. The bimodal distribution suggests that a clear cohort of pts exists at the time of relapse/study entry who are positive for sECD HER2. Analyses are evaluating whether subsequent changes in sECD HER2 levels occur over time during therapy, whether seroconversion predicts for a shorter time to relapse during letrozole monotherapy, and whether any differences exist in sECD HER2 levels over time for pts treated with letrozole plus lapatinib are ongoing. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3147.