Stability of Estrogen Receptor and HER2 Status Following Trastuzumab and Polychemotherapy Regimen.
Authors: Gong Y. , Han E. , Xiao C. , Gonzalez-Angulo A. , Sneige N. 
Published: December 2010

Background: ER and HER2 status are important to determine a patient's eligibility to receive endocrine therapy and anti-HER2 (trastuzumab) therapy, respectively. However, whether the status of ER and HER2 is stable after administration of trastuzumab and chemotherapy remains controversial. To date, there have been rare studies describing a change of ER and HER2 status following such treatment. We herein examined our experience to further elucidate this issue.Material and methods: Our study included 24 patients who had been diagnosed with breast cancer from 12/1996 to 1/2005 with known ER and HER2 status in both primary and paired relapse tumors (9 distant and 15 locoregional). All of the patients had HER2-positive primary carcinoma and had been treated with trastuzumab administered concomitantly or after polychemotherapy. Fifteen patients had ER-positive primary carcinomas. ER status was defined as positive if ≥10% of tumor cells demonstrated nuclear staining by immunstaining. HER2 status was defined as positive if an immunostaining demonstrated 3+ staining and/or FISH demonstrated a HER2:CEP17 gene copy ratio ≥2.0. The receptor status was tested on tissue sections (for primary tumors) or on FNA samples (for metastases). We evaluated the agreement of ER and HER2 status between primary breast carcinomas and paired metastatic tumors.Results: The time elapsed between the diagnosis of the primary breast carcinoma and sampling of the paired metastatic tumor was &gt;24 months for all patients but one (mean interval, 75 months). Before the metastatic tumors were sampled, the duration of trastuzumab therapy had been ≥12 month in 18 patients; in some patients the treatment had been intermittent. All 15 patients with ER-positive primary carcinoma had received adjuvant endocrine therapy, including tamoxifen, aromatase inhibitor or both, and 7 of them had completed 5 years of treatment. ER status of primary and metastatic tumors agreed in 20 of the 24 patients, with a concordance rate of 83.3% (95% CI, 68.42% - 98.24%), and Cohen's kappa coefficient of 0.6596 (95% CI, 0.3598 - 0.9593). Of the four patients with discordant ER status, three had ER-positive primary tumors but ER-negative metastatic tumors, and one had ER-negative primary tumor but ER-positive metastatic tumor. Notably, in two of the four patients, the percentage of ER-positive tumor cells in the primary carcinomas was close to the cutoff (10%), indicating the potential of scoring difficulty. Negative HER2 status was found in three (12.5%) of the 24 metastatic tumors. One of the three patients had two primary carcinoma nodules: one HER2-positive and the other HER2 negative. It is possible that negative HER2 status in the metastatic tumor may result from a metastasis from the HER2-negative primary tumor, rather than a true discrepancy.Conclusions: Change in ER status was found in 17% relapse tumors, mostly from positive to negative. Converting HER2 status from positive to negative was seen in 13% patients. Overall, trastuzumab and chemotherapy do not significantly alter ER and HER2 status. However, a larger study is required to confirm whether the discordant receptor status is due to true biologic shift or other factors (i.e., technical and interpretation variation).

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5097.