Abstract P4-06-06: Comparison of HER2, estrogen and progesterone receptor expression profiles of primary tumor and synchronous axillary lymph node metastases in 149 breast cancer patients - indicating tumoral heterogeneity
Authors: Weydandt Laura , Kreklau Anne , Oehme Florian , Horn Lars Christian , Aktas Bahriye 
Published: March 2020

Background: Tumor heterogeneity in terms of comparison between receptor expression profiles (ER, PR and HER2) of primary core needle biopsies (CNB) and definitive lymph node histo-pathologic examination is an evolving research field with unknown potential in terms of individual oncological treatment. Yet, heterogeneity is merely common as a different receptor expression between primary tumor versus metastatic disease. Thus, data on primary receptor heterogeneity between primary tumor and synchronous lymph node metastasis is rare. Primary aim of this trial is to present data on the epidemiologic aspect of tumor heterogeneity with synchronous lymph node metastases (LNM) in breast cancer patients.

Methods: We retrospectively analyzed 149 consecutive patients with breast cancer and synchronous LNM who undergone oncologic surgery (sentinel lymph-node biopsy: 66,4%, axillary lymph-node dissection: 33,6%) between 2008 and 2018 at the university hospital Leipzig, Germany. Patients underwent operation without any preoperative therapy, with neoadjuvant chemotherapy or with neoadjuvant hormone therapy in 109 (73,2%), 30 (20,1%) and 10 (6,7%) cases, respectively.

Formalin-fixed and paraffin-embedded (FFPE-material) were routinely examined immunohistochemically according to the ASCO/CAP guidelines using Ventana-platform. The results for ER, PR and HER2 were analyzed case-by-case comparing results from the CNB of the primary tumor within the breast and axillary LNM. Proliferative activity was determined by MIB-1 immunohistochemistry and according to well established guidelines, the tumors were grouped into the different intrinsic subtypes as luminal A and B, HER2-enriched and triple-negative by the different immunohistochemical staining results.

Results: Median patient age was 61 years with most frequent tumor entity (75,8%) being an invasive-ductal adeno carcinoma. 115 (77,2%) patients had either a T1 or T2 stadium.

Overall there were 61 (40,1%) patients who had at least one receptor change, with 16 patients with two receptor changes. The discordance rates between primary tumors and axillary LNM were 13,4% for HER2, 10,1% for ER and 28,2% for PR. Totally in 69 receptor changes the receptor was initially positive and changed to negative (receptor-loss), whilst in 8 cases a receptor was positive that was initially negative (receptor-gain).

Out of 77 receptor changes, 18 were after neoadjuvant chemotherapy, 5 after neoadjuvant endocrine therapy and 54 changes were without any neoadjuvant treatment. Influencing factor in estrogen receptor changes in the competitive analysis was a younger age (p-value 0.01, medium age 51.27 years; PR receptor change, medium age: 60,88 years; HER2 receptor change: medium age: 61,65 years).

Conclusions: Our results imply the high frequency of subtype differences between primary tumor and LNM. This could be explained by intra-tumor heterogeneity. Subtype changes should be taken into account for an optimal and individual treatment. Larger studies are necessary to validate these data and gain further information.

Citation Format: Laura Weydandt, Anne Kreklau, Florian Oehme, Lars Christian Horn, Bahriye Aktas. Comparison of HER2, estrogen and progesterone receptor expression profiles of primary tumor and synchronous axillary lymph node metastases in 149 breast cancer patients - indicating tumoral heterogeneity [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-06-06.