Abstract P1-04-06: Discordance of the ER- and HER2-status on disseminated tumor cells compared to the primary tumor in patients with early breast cancer

Abstract

Background: Differences in ER- and HER2-expression on metastases compared to the primary tumor (PT) are a known phenomenon and may have clinical implications in respect of targeted systemic treatment approaches. The aim of this study was to evaluate both ER- and HER2-status on disseminated tumor cells (DTCs) in the bone marrow (BM) of patients (pts) with early breast cancer (EBC) and to compare these with the corresponding PT. Methods: BM aspirates were obtained at the time of first surgery. After Ficoll enrichment for mononuclear cells two cytospins with 106 BM cells were evaluated for ER-, HER2- and cytokeratin (CK) -expressions simultaneously by immunocytochemistry using a triple fluorescence staining method with antibodies directed against human ER (secondly labeled with Cy3, red), HER2 (Coumarin-AMCA, blue) and CK (DyLight488, green). The manual analysis was conducted using a computerized fluorescence microscope (Axioskop, Zeiss, Germany). Criteria for CK- and HER2-positivity were the ring-like appearance of the respective membrane stainings and for ER-expression a nuclear staining. Only pts with the detection of CK positive cells (DTC+) and known ER- and HER2-status of the PT (n = 54) were selected for this analysis. Results: The median number of DTCs was 13 (range 1-95; total number of DTCs detected: 1082). 40 (74%) of the pts had at least one ER-positive (pos) DTC, 24 (44%) at least one HER2-pos DTC, 14 (26%) at least one ER-pos/HER2-pos DTC, and 50 (93%) at least one ER-negative/HER2-negative (neg) DTC, while 10 (19%) pts had only ER-neg/HER2-neg DTCs. The concordance rate between ER-status on DTCs and PT was 74%. Pts with an ER-pos PT were significantly more likely to have at least one ER-pos DTC (34 out of 42) than pts with an ER-neg PT (6 out of 12; Chi-square test, χ2 = 4.66, p = 0.031). 39 (93%) of the 42 pts with ER-pos PT had at least 1 ER-neg DTC. The concordance rate between HER2-status on DTCs and PT was 52%. The probability of having at least one HER2-pos DTC was not related to the HER2-status of the PT (Chi-square test, χ2 = 0.34, p = 0.56). 22 (46%) of the 48 pts with a HER2-neg PT had at least one HER2-pos DTC. All of the 6 pts with a HER2-pos PT had at least one HER2-neg DTC. 7 out of 10 pts with a triple-neg PT had at least one DTC pos for ER, HER2 or both. Further the heterogeneity of the ER- and HER2-expression on DTCs compared to the PT for different DTC counts was evaluated. We detected all possible combinations of ER- and HER2-experssion on DTCs regardless of the respective status of the PT. Conclusions: Our study confirms that the ER- and/or HER2-status on DTCs may differ compared to the PT. This discordance could be especially important for pts with a triple-neg PT and ER-pos or HER2-pos DTCs, since they might respond favorably to an endocrine or HER2-targeted therapy. On the other hand, the presence of ER-neg or HER2-neg DTCs in pts with ER-pos or HER2-pos PT might explain some of the failures of adjuvant endocrine or HER2 targeted therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-06.