Changes in estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status with time: Discordance rates between primary and metastatic breast pathology samples

Abstract

1024 Background: The occurrence of changes in tumor receptor profile (ER, PR and HER-2/neu) between primary and metastatic tissue has been recognised and may have significant treatment implications. Previous reports on receptor discordance rates have tended to be from sub-studies of clinical trials. We sought to evaluate the degree of ER, PR and HER-2/neu receptor discordance in patients treated at two Canadian cancer centres. Methods: Archival data was collected on patients for whom tissue from both primary and metastatic sites was available. Patients with recurrences in the breast or axilla were excluded. ER, PR and HER-2/neu status in the primary and metastasis were compared. Additional information including adjuvant therapy and time to metastasis biopsy was gathered. Results: To date, data is available on 80 patients. Hormone receptor (HR) status was available for 96% of primaries and 56% of metastases. HR status on both the primary and the metastasis was performed in 51% of cases. The discordance rate for ER was 21% (2-sided p=0.0096). 12% of patients changed from ER+ to ER- and 9% changed from ER- to ER+. The discordance rate for PR was 37% (2-sided p=0.0001), with all of these patients changing from PR+ to PR-. No significant HR discordance was found among different adjuvant hormone therapy subgroups. There was no correlation between HR discordance and time to rebiopsy. No discordance for HER-2/neu was found. Conclusions: Significant discordance for HR status was observed, 21% for ER and 37% for PR. HER-2/neu discordance was not observed. We are currently exploring the practical implications of these discordance rates on the management of advanced breast cancer patients in a prospective trial. No significant financial relationships to disclose.

Stability of estrogen receptor status in breast carcinoma

“…Holdaway et al reported a significant reduction of ER expression in chest wall recurrences and visceral metastases compared with locoregional lymph node metastases, raising a possibility that tumor cells with different ER expression may be selected and adapted to grow in different anatomical sites 10. More recent studies, however, demonstrated similar rates of discordance for local recurrences and distant metastases 6, 13, 21, 22. Consistent with this, our data did not show a significant influence of metastatic site on ER concordance rate.…”

“…Given the fact that metastatic breast carcinoma often occurs several years after the initial diagnosis of primary carcinoma, and many patients have already received a variety of systemic therapies by the time of relapse, controversy remains as to whether ER status obtained from a primary tumor can reliably guide therapeutic decisions for metastatic disease of the same patient and whether ER testing needs to be repeated for the metastatic carcinoma. In earlier studies, the reported concordance between primary and metastatic tumors varied widely from 55% to 95% 4‐15. It is notable that the majority of these studies included relatively small cohorts of patients and used the ligand‐binding assay to test ER, which is less reliable than IHC 16…”

Distinct MR Imaging Features of Triple‐Negative Breast Cancer with Brain Metastasis

“…24 In BCs, the commonly used markers, ER, PR, Ki-67, or HER2, also display discordance between the primary and recurrent lesion. 25,26 Therefore, rebiopsy of the metastatic lesion to confirm the biological concordance to primary tumor is crucial upon initiation of treatment to relapsed disease. However, clinicians do not regularly perform rebiopsy to the BM.…”

Estrogen, Progesterone, and Her-2/neu Receptor Expression Discrepancy in Primary Tumors and In-Breast Relapse in Patients with Breast Cancer

“…Patients with Her-2/neu overexpressive breast cancer can be treated with the humanized antibody Trastuzumab. Some studies have reported hormone-receptor status discordance rates of 10-54% between primary and recurrent breast tumors (3)(4)(5)(6)(7)(8). The mechanisms of change of hormone receptor and Her-2/neu expression have not been explicitly identified.…”