Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer

1999 ◽  
Vol 17 (5) ◽  
pp. 1474-1474 ◽  
Author(s):  
Jennet M. Harvey ◽  
Gary M. Clark ◽  
C. Kent Osborne ◽  
D. Craig Allred
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Clinical Outcome ◽  
Ligand Binding ◽  
Endocrine Therapy ◽  
Binding Assay ◽  
Adjuvant Endocrine Therapy ◽  
Ligand Binding Assay ◽  
Breast Cancers ◽  
Er Status

PURPOSE: Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS: ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS: An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION: IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.

scholarly journals Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Muriel Lainé ◽  
Sean W. Fanning ◽  
Ya-Fang Chang ◽  
Bradley Green ◽  
Marianne E. Greene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Growth ◽  
Ligand Binding ◽  
Endocrine Therapy ◽  
Breast Cancers ◽  
Primary Tumor Growth ◽  
Wild Type ◽  
Tumor Growth And Metastasis ◽  
Anti Tumor Activity

Abstract Background Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy. Lasofoxifene is a selective estrogen receptor modulator with benefits on bone health and breast cancer prevention potential. This study investigated the anti-tumor activity of lasofoxifene in breast cancer xenografts expressing Y537S and D538G ERα mutants. The combination of lasofoxifene with palbociclib, a CDK4/6 inhibitor, was also evaluated. Methods Luciferase-GFP tagged MCF7 cells bearing wild-type, Y537S, or D538G ERα were injected into the mammary ducts of NSG mice (MIND model), which were subsequently treated with lasofoxifene or fulvestrant as single agents or in combination with palbociclib. Tumor growth and metastasis were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. Results As a monotherapy, lasofoxifene was more effective than fulvestrant at inhibiting primary tumor growth and reducing metastases. Adding palbociclib improved the effectiveness of both lasofoxifene and fulvestrant for tumor suppression and metastasis prevention at four distal sites (lung, liver, bone, and brain), with the combination of lasofoxifene/palbociclib being generally more potent than that of fulvestrant/palbociclib. X-ray crystallography of the ERα ligand binding domain (LBD) shows that lasofoxifene stabilizes an antagonist conformation of both wild-type and Y537S LBD. The ability of lasofoxifene to promote an antagonist conformation of Y537S, combined with its long half-life and bioavailability, likely contributes to the observed potent inhibition of primary tumor growth and metastasis of MCF7 Y537S cells. Conclusions We report for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. The results demonstrate the potential of using lasofoxifene as an effective therapy for women with advanced or metastatic ER+ breast cancers expressing the most common constitutively active ERα mutations.

An enzyme immunoassay compared with a ligand-binding assay for measuring progesterone receptors in cytosols from breast cancers.

1988 ◽  
Vol 34 (6) ◽  
pp. 1116-1118 ◽  
Author(s):  
C M Smyth ◽  
D E Benn ◽  
T S Reeve
Keyword(s):  
Breast Cancer ◽  
Ligand Binding ◽  
Least Squares ◽  
Enzyme Immunoassay ◽  
Binding Assay ◽  
Progesterone Receptors ◽  
Ligand Binding Assay ◽  
Breast Cancers ◽  
Best Fit ◽  
Very High

Abstract To assay progesterone receptor (PR), we compared Abbott's enzyme immunoassay (PR-EIA) with a ligand-binding assay involving dextran-coated charcoal (PR-DCC), using cytosols prepared from 109 breast-cancer biopsies. Results by the two PR methods agreed well. Least-squares analysis produced a line of best fit having a slope of 0.88, an intercept on the PR-EIA axis of 16 fmol per milligram of protein, and a correlation coefficient (r2) of 0.87. To evaluate whether accurate PR-EIA measurements could be obtained on stored cytosols, we compared PR-EIA values for fresh cytosols with values for cytosols stored for various lengths of time up to 13 weeks. Agreement was excellent, especially when the samples showing very high binding (greater than 600 fmol per milligram of protein) were excluded. The lines of best fit after least-squares analyses of the remaining values had slopes between 1.0 and 1.1, intercepts less than 3 fmol/mg, and r2 all greater than 0.91.

Breast cancers negative for estrogen receptor but positive for progesterone receptor, a true entity?

1987 ◽  
Vol 5 (4) ◽  
pp. 662-666 ◽  
Author(s):  
D T Kiang ◽  
R Kollander
Keyword(s):  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Staining Method ◽  
Binding Assay ◽  
Assay Method ◽  
Breast Cancers ◽  
Antibody Method ◽  
Steroid Binding ◽  
Rare Group ◽  
Er Status

By the conventional steroid-binding assay method for receptor, 3% of 1,095 primary breast cancers (or 10.6% of 263 premenopausal tumors) were classified as negative for estrogen receptor (ER), but positive for progesterone receptor (PR). The true ER status in this rare group of tumors was further investigated by the enzyme-immunoassay (EIA) or immunocytochemical (ICA) staining method using monoclonal antibodies H222 and D547. Immunoreactive ER was present in nine ER-/PR+ tumors studied, whereas it was not detectable in nine age-matched ER-/PR- tumors. Immunoreactive ER was also present in 24 ER+ breast cancers studied, and was particularly higher in tumors that were PR+. Measurement of immunoreactive ER by monoclonal antibody method provides certain advantages over the conventional dextran-coated charcoal (DCC) method, especially in ER-/PR+ tumors.

Correlation of an Estrogen Receptor-related Phosphoprotein with Histopathological Features in Breast Cancer

1989 ◽  
Vol 4 (2) ◽  
pp. 95-102
Author(s):  
R.M. Tomasino ◽  
E. Daniele ◽  
R. Nuara ◽  
V. Morello ◽  
M. Salvato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Estrogen Receptor ◽  
Breast Carcinoma ◽  
Breast Cancers ◽  
Histopathological Features ◽  
Histological Types ◽  
Biological Meaning ◽  
Er Status

A series of 65 cases of different histological types of breast carcinoma was investigated for the immunohistochemical location of the estrogen receptor-related, 29 kD phosphoprotein using the ER-D5 monoclonal antibody. The ER-D5 response is heterogeneous in relation to some therapeutic limitations and is correlated with histopathological features of the tumors and survival. The main parameters for evaluation of breast cancers are reviewed, both those that are statistically correlated and those that are not apparently always correlated but are known to have considerable biological meaning, such as the ER-status of tumors.

Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in estrogen receptor-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21160-e21160
Author(s):  
Ji sun Kim ◽  
Wonshik Han ◽  
Jee Man You ◽  
Hee-Chul Shin ◽  
Soo Kyung Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Breast Density ◽  
Adjuvant Endocrine Therapy ◽  
Absolute Difference ◽  
Mammographic Breast Density ◽  
Short Term ◽  
Er Positive ◽  
Positive Breast Cancer

e21160 Background: Previous studies showed that anti-estrogen therapy lowers mammographic breast density (MD). We hypothesized that the short-term change of breast density can be a surrogate marker predicting response to adjuvant endocrine therapy (ET) for breast cancer. Methods: We analyzed data of 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET including tamoxifen and aromatase inhibitor. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction was defined as an absolute difference between the MD of two mammography images: taken preoperatively and 8-20months after the start of adjuvant ET.. Results: After median follow up of 68.8 months, overall recurrence rate was 7.5% (80/1065). Mean MD reduction was 5.9% (-17.2 to 36.9). In a logistic regression analysis, age<50, high preoperative MD, and longer interval between start of ET to the 2nd mammogram were significantly associated with higher MD reduction (p value<0.05). In a survival analysis using Cox model, tumor size (>2cm), lymph node positive, high Ki-67 (≥10%), and lower MD reduction were independent factors significantly associated with recurrence-free survival (p<0.05). The hazard of recurrence increased proportionally according to the less degree of MD reduction. Conclusions: MD change during short-term use of adjuvant ET was a significant predictive factor for long-term recurrence in ER-positive breast cancer. It is urgent to develop effective treatment strategy in patients who have less MD reduction in spite of about 1 year of ET.

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