Discordances in Estrogen Receptor Status, Progesterone Receptor Status, and HER2 Status Between Primary Breast Cancer and Metastasis

Abstract

Background. The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance. Methods. Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3ϩ in immunohistochemistry or if amplification ratio was Ͼ2 in fluorescent in situ hybridization. Results. From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p ϭ 4 ϫ 10), and HER2 in 4% of lesions (p ϭ .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed. Conclusions. This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting. TheOncologist2013;18: 667-674 Implications for Practice: Discordance in estrogen receptor and progesterone receptor expression between the primary breast tumor and the corresponding metastatic lesion was high (17% and 29%, respectively), whereas HER2 status remained stable (4% of discordance). Previous chemotherapy, and specifically anthracycline-based chemotherapy, was associated with a switch in estrogen receptor status. Further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting. In the era of a more personalized approach to medicine and of genomic investigations of tumors, reliable and recent evaluation of tumor prognostic and predictive factors remains a challenge. INTRODUCTIONThe treatment of metastatic breast cancer (mBC) is complex with few recognized therapeutic standards, particularly after the first line of treatment. Multiple fa...

Profiles of brain metastases: Prioritization of therapeutic targets

“…Consistent with the literature, we identified less frequent expression of hormone receptor expression in breast cancer brain metastases26, 27, 28—although in a much larger patient cohort and with the novel extension of this to androgen receptor (AR) status. Hormone receptor loss is a known marker of aggressive disease, negative prognosis and limited treatment options.…”

Synchronous Orbital and Gastric Metastasis of Invasive Lobular Breast Carcinoma, Mimic Primary Gastric Carcinoma-Case Report

“…In contrast, c-erb-B2 showed only 4% discordance rate. Chemotherapy, and especially anthracyclinebased chemotherapy, was associated with switch in ER status [14]. In this case, ER and PR showed positivity on metastatic gastric lesion that is agreement with primary breast disease; consistent with metastatic breast carcinoma.…”

“…Curtit et al [14] compared IHC findings between primary breast malignancy and metastatic lesion after treatment. Forty two patients showed discordance on IHC analysis, a switch in receptor status was verified for ER in 17% and PR in 29%.…”

Letter to the Editor regarding the paper by Aurilio et al., A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

“…It is well known that a considerable controversy concerns the issue of hormone receptors (HRs) expression as well as HER2 status between primary breast carcinomas (BC) and metastatic sites from the same patient, as elsewhere reported in literature [1][2][3][4][5]. In particular, the discordance between primary BC and metastases from negative to positive and vice versa potentially affects the treatment regimen [5]; therefore, it has been suggested that neoplastic tissue of metastatic lesions should be systematically re-biopsied to optimally re-assess HR as well as HER2 [1,2,[4][5][6][7][8].In their meta-analysis, focusing on HER2 status, Aurilio et al documented that the pooled discordance proportion with respect to the primary breast tumour was 10% for distant metastases and 6% for loco-regional relapses. Moreover, a different pooled discordant proportion was found on the basis of the different utilised technique, since it was 10% in studies using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), but 5% in studies using IHC only; therefore, they conclude the observed discrepancy was not merely due to technicality.…”

“…In the paper, the Authors have performed a meta-analysis of the studies published in the literature concerning the discordance rate in oestrogen receptor (ER), progesterone receptor (PgR) and HER2 status between primary tumour and corresponding relapse. It is well known that a considerable controversy concerns the issue of hormone receptors (HRs) expression as well as HER2 status between primary breast carcinomas (BC) and metastatic sites from the same patient, as elsewhere reported in literature [1][2][3][4][5]. In particular, the discordance between primary BC and metastases from negative to positive and vice versa potentially affects the treatment regimen [5]; therefore, it has been suggested that neoplastic tissue of metastatic lesions should be systematically re-biopsied to optimally re-assess HR as well as HER2 [1,2,[4][5][6][7][8].…”