Abstract P1-01-09: Comparison of HER2, estrogen and progesterone receptor expression profiles of primary tumor, synchronous axillary lymph node metastases and circulating tumor cells in early breast cancer patients
Authors: Aktas B , Westerwick D , Mairinger F , Kasimir-Bauer S , Kimmig R , Schmid K , Bankfalvi A 
Published: March 2017

Background:Targeted systemic therapy in early breast cancer with synchronous lymph node metastasis is currently based on the expression of the hormone receptors (ER/PR ≥1%) and overexpression of HER2 in the primary tumor. However, the expression of these predictive markers on lymph node metastases as well as on circulating tumor cells (CTCs), the precursors of metastatic disease, has not yet been taken into account. The aim of the present study was to compare the HER2/ER/PR expression profiles of primary tumors, synchronous lymph node metastases and circulating tumor cells in early breast cancer patients and relate the results to 5-year overall (OS) and disease-free survival (DFS).

Patients and Methods:76 patients with early breast cancer diagnosed between 2006 and 2010 were enrolled in this study. Blood was obtained at the time of first diagnosis of disease and analyzed for CTCs using the AdnaTest BreastCancer (Qiagen Hannover GmbH) for the expression of EpCAM, MUC-1, HER2, ER and PR respectively.

Formalin-fixed and paraffin-embedded archival tissues of the primary tumors and the lymph node metastases were analyzed by two pathologists. ER, PR and HER2 expression was assessed by fully-automated immunohistochemistry (Ventana medical Systems, Tucson, AZ, USA) and HER2/CEN17 dual chromogenic in situ hybridization (Zytomed Systems, Berlin, Germany) according to modified ASCO/CAP guidelines (2010 and 2013, respectively).

Results: The detection rate for CTCs was 22% (17/76 patients). In the primary tumors, the expression rate of HER2 was 16% (13/76 patients), 78% for ER (61/76 patients) and 75% for PR (57/76 patients) respectively. Changes in biomarker profiles between primary tumors, metastases and CTCs, as a whole, were observed in 89% of the cases (68/76). The discordance rates between primary tumors and lymph node metastases were 10% for HER2 (p&lt;0.001), 5% for ER (p= p&lt;0.001) and 11% for PR (p&lt;0.001). The intrinsic subtypes between primary tumors and lymph node metastases changed in 16% of all cases (12/76 patients; gain of HER2 in four, activation of HRs in three cases, loss of HER2 in three and loss of HRs in one case becoming triple negative). Of note, both OS and DFS of patients with subtype discordance were reduced to a median of 41 months (mean: 39) vs 56 months (mean: 51).

CTCs were either triple negative or HER2 positive. Discordance rates for HER2, ER and PR status compared to the primary tumors were 16% (12/76 patients), 83% (63/76 patients)and 72% (55/76 patients), respectively. Discordant rates between lymph node metastases and CTCs were 25% for HER2 (19/76 patients), 82% for ER (62/76 patients) and 72% for PR (55/76 patients).

Conclusion: Our preliminarily results demonstrate, that changes in molecular profiles are the rule rather than the exception throughout tumour progression in breast cancer. In cases with discordant biomarker profiles, prognosis seems to follow the subtype of lymph node metastasis. Biomarker or subtype shift may be of essential therapeutic significance for individual patients.

Citation Format: Aktas B, Westerwick D, Mairinger F, Kasimir-Bauer S, Kimmig R, Schmid K, Bankfalvi A. Comparison of HER2, estrogen and progesterone receptor expression profiles of primary tumor, synchronous axillary lymph node metastases and circulating tumor cells in early breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-09.