Estrogen and progesterone receptor content of primary and secondary breast carcinoma: Influence of time and treatment

doi:10.1016/0277-5379(87)90285-9

European Journal of Cancer and Clinical Oncology

Volume 23, Issue 6, June 1987, Pages 819-826

European Journal of ...

https://doi.org/10.1016/0277-5379(87)90285-9 Get rights and content

Abstract

ER and PgR concentrations were assayed in primary and secondary breast carcinoma specimens from patients classified into 3 groups: (1) both specimens excised on the same occasion (61 patients); (2) specimens obtained on separate occasions with no intervening treatment (43 patients; (3) specimens obtained on separate occasions with intervening chemotherapy and/or irradiation (25 patients). There were highly significant linear correlations (P < 0.001) between the concentrations of ER (expressed as log₁₀) in primary and secondary specimens in all groups. The relationship between PgR concentrations in primary and secondary specimens in groups 1 and 2 was highly significant, although there appeared to be a greater tendency for loss of PgR in sequential, than in simultaneous secondary biopsies.

When expressed in terms of hormone receptor status (HRS), the same rate of discordance was observed in groups 1 and 2 (30% when concentrations were expressed in terms of cytosol protein). In group 1 the major cause of discordance was the occurrence of receptor +ve secondaries in association with receptor −ve primaries, possibly because of the high cellularity of many involved axillary nodes. In group 2, the major cause of discordance was the occurrence of receptor −ve secondaries derived fropm receptor +ve primaries. In both groups discordance in PgR status was more frequent than in ER status. In group 3, overall discordance in HRS was 24% and was due equally to ER and PgR; however, the high concordance rate for PgR was probably due to the fact that the tumours were initially PgR −ve, and the secondaries were also −ve.

These results confirm that ER content tends to be stable, even after long periods of time and the administration of chemotherapy and/or irradiation. Progesterone receptor content is much less stable, and may decrease during quite short time intervals even in the absence of treatment.

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Strategies for obtaining bone biopsy specimens from breast cancer patients – Past experience and future directions
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Citation Excerpt :
We also discuss some of the challenges faced by each project and how we have tried to incorporate these lessons into subsequent projects (Table 1). With significant hormone status discordance between primary and metastatic sites in breast cancer patients having been reported [16–18], acquisition of metastatic tissue may have important implications in planning subsequent treatments. Amir et al. reported that biopsy of any site of metastatic recurrence at the time of first metastases led to change in management of 14% of women with breast cancer (95% CI, 8.4% to 21.5%) [19], as a result of change in the expression of ER, PR and Her2 receptors [19].
Cancer and its treatment can have multiple effects on the bone. Despite the widespread use of in vivo and in vitro models, it is still necessary to understand these effects in humans. Obtaining human bone biopsies is technically challenging and in this article we review the experiences from the Ottawa Bone Oncology Program.
A series of bone biopsy studies in breast cancer patients with and without bone metastasis have been performed. We reviewed the results of these studies and present them in a descriptive manner. We discuss lessons learned from each project and how they have affected future directions for research.
Since 2009, 5 studies have been performed accruing 97 breast cancer patients. Study endpoints have ranged from comparing the yield of malignant cells from CT-guided versus standard iliac crest biopsies, to studies assessing the feasibility of micro-CT analysis on Jedhadi trephines to evaluate bisphosphonate effects on bone micro-architecture. More recently, we have assessed the feasibility of performing repeat bone biopsies in the same patient as well as evaluating the practicality of obtaining bone tissue at the time of orthopaedic surgery.
Human bone tissue is an important biological resource. Our experience suggests that obtaining bone biopsies is feasible and can yield adequate amount of tumour cells for many studies. However, these remain technically challenging specimens to obtain and given the rapid advances in cancer therapeutics and the use of potent adjuvant bone-targeted agents, more centres need to be involved in these types of studies.
A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases
2014, European Journal of Cancer
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All the reported P values were two sided. Forty-eight studies were identified (Fig. 1, [9–56]) and their main characteristics are reported in the Appendix. ER, PgR and HER2 status in the primary tumour and corresponding relapses were available in 33, 24 and 31 studies, respectively.
The discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed.
A literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions.
We selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I² = 91%, p < 0.0001), PgR (I² = 79%, p < 0.0001) and HER2 (I² = 77%, p < 0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16–35%) for ER, 33% (95% CI: 29–38%) for PgR and 8% (95% CI: 6–10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p = 0.0183), respectively. The same figures were 46% and 15% for PgR (p < 0.0001), and 13% and 5% for HER2 (p = 0.0004).
Our findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.
An evaluation of the impact of technical bias on the concordance rate between primary and recurrent tumors in breast cancer
2013, Breast
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Knowing HR and HER2 status is therefore essential, for it not only provides prognostic information but it is also used to predict response to specific treatment. Many retrospective series and some prospective studies [3–15] have reported changes in HR status and HER2 expression between PT and RT in breast cancer. To our knowledge, however, changes in the determination of these receptors have not been biologically explained even though these changes may have an impact on the clinical management of MBC patients [15].
Whether or not to biopsy the metastasis in recurrent breast cancer has become mired in controversy. Several studies have shown an important discordance of the immunohistochemical (IHC) determinations for ER, PR and HER2 between primary (PT) and recurrent tumors (RT). Yet it remains unknown within this what impact technical issues have. The aim of our study was to assess whether technical variability might have an impact on the concordance between PT and RT.
IHC determinations in paired biopsies from PT and RT were compared under routine vs study conditions. In the former, pathological analysis reproduced the conditions used in the routine of a University Pathology Department. In the latter, in a technical bias-minimizing manner, samples were re-assessed at the same timing and by two independent observers.
128 paired biopsies from 64 patients were analyzed under both conditions. Concordance under routine vs study conditions for ER was 66% vs 93.4% (p = 0.001), for PR 58.7% vs 80.3% (p = 0.064) and for HER2 86.8% vs 96.8% (p = 0.25). Kappa index under routine versus study conditions for ER was 0.27 vs 0.79 (p = 0.002), for PR 0.26 vs 0.39 (p = 0.47) and for HER2 0.67 vs 0.9 (p = 0.14).
Although discordance rate between PT and RT decreased under conditions minimizing technical issues, some discordant cases appeared not to be subjected to this confounding factor. Either for clinical practice or for future studies reassessment of PT in recurrent breast cancer should be encouraged.
Should liver metastases of breast cancer be biopsied to improve treatment choice?
2011, Annals of Oncology
Citation Excerpt :
The discordance rates for ER, PgR, and HER2 status between primary tumor and liver metastases were 14.5%, 48.6%, and 13.9%, respectively, which led to change in therapy for 31 of 255 patients (12.1%). Other studies addressed our questions but the results are conflicting [6–30]. A recent study prospectively investigated concordance in receptor status between primary tumor and distant metastases and assessed the impact of any discordance on patient management [6].
Currently, the acquisition of tissue from metastatic deposits is not recommended as a routine practice. Our aim was to evaluate the discordance rate of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) receptor status between primary tumor and liver metastases and its potential impact on treatment choice.
We retrospectively analyzed a database including 1250 ultrasound-guided liver biopsies carried out at the European Institute of Oncology from August 1999 to March 2009. ER, PgR, and HER2 status were determined by immunohistochemistry and/or FISH. Differences between proportions were evaluated using Fisher’s exact test.
We identified 255 consecutive patients with matched primary and liver tissue samples. Changes in ER status were observed in 37 of 255 patients (14.5%). Changes in PgR status were observed in 124 of 255 patients (48.6%). Changes in HER2 status were observed in 24 of 172 assessable patients (13.9%). We observed a discordance in receptor status (ER, PgR, and HER2) between primary tumor and liver metastases, which led to change in therapy for 31 of 255 of patients (12.1%).
Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out, since it is likely to impact treatment choice.
Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases?
2009, Annals of Oncology
Decisions about systemic treatment of women with metastatic breast cancer are often based on estrogen receptor (ER), progesterone receptor (PgR), and Her2 status of the primary tumor. This study prospectively investigated concordance in receptor status between primary tumor and distant metastases and assessed the impact of any discordance on patient management.
Biopsies of suspected metastatic lesions were obtained from patients and analyzed for ER/PgR and Her2. Receptor status was compared for metastases and primary tumors. Questionnaires were completed by the oncologist before and after biopsy to determine whether the biopsy results changed the treatment plan.
Forty women were enrolled; 35 of them underwent biopsy, yielding 29 samples sufficient for analysis; 3/29 biopsies (10%) showed benign disease. Changes in hormone receptor status were observed in 40% (P = 0.003) and in Her2 status in 8% of women. Biopsy results led to a change of management in 20% of patients (P = 0.002).
This prospective study demonstrates the presence of substantial discordance in receptor status between primary tumor and metastases, which led to altered management in 20% of cases. Tissue confirmation should be considered in patients with clinical or radiological suspicion of metastatic recurrence.
(17α,20E/Z)-Iodovinyl- and 16α-iodo-18-homoestradiol derivatives: Synthesis and evaluation for estrogen receptor imaging
2000, Steroids
Three new ¹²⁵I-radioiodinated estrogens featuring a 13β-ethyl instead of the natural 13-methyl group, i.e. 18-homoestradiols, were synthesized and evaluated as potential estrogen receptor imaging agents. The 16α-iodo-18-methylestradiol and the ¹²⁵I-labeled analog were synthesized from the corresponding 16β-bromo analog by the halogen-exchange method. The cis-bromohydrin precursor was obtained by bromination of an estrone enolacetate, followed by epimerization and reduction. The isomeric (17α,20E/Z)-iodovinyl-18-methylestradiols were prepared via the vinyltin intermediates. Treatment of 18-methyl-17α-ethynylestradiol with tri-n-butyltin hydride, in the presence of azobisisobutyronitrile as catalyst and heating at 90–100°C afforded the (17α,20E)-tri-n-butylstannyl isomer as the major product. Changing the catalyst for triethyl borane, at room temperature, mainly gave the 20Z-isomer. The nca ¹²⁵I-labeled analogs were obtained from their corresponding tin intermediates upon treatment with [¹²⁵I]NaI in the presence of H₂O₂. The 16α-[¹²⁵I]iodo- and isomeric (17α,20E/Z)-[¹²⁵I]iodovinyl-18-methylestradiols were evaluated for estrogen receptor-mediated uterine uptake in immature female rats. Homologation of the C13-methyl group did improve the uterine uptake of the iodovinyl derivatives, but also increased blood retention, resulting in lower target uptake ratios. In the case of the 16α-iodo analog uterine retention decreased upon C13-homologation.

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: Sources of support: Partial funding by the Ontario Cancer Treatment and Research Foundation and the Women's college Hospital Research Fund.

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Estrogen and progesterone receptor content of primary and secondary breast carcinoma: Influence of time and treatment

Abstract

Eur J Cancer Clin Oncol

Eur J Cancer Clin Oncol

J Biol Chem

Clin Biochem

Eur J Cancer Clin Oncol

Eur J Cancer

Multiple estrogen receptor assays in human breast cancer

Cancer Res

Multiple progesterone receptor assays in human breast cancer

Cancer Res

Changes of steroid hormone receptor content by chemotherapy and/or endocrine therapy in advanced breast cancer

Cancer

Changes in multiple and sequential estrogen receptor determinations in breast cancer

Cancer

Estrogen receptor variations in neoplastic tissue during the course of disease in patients with recurrent breast cancer