scholarly journals Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial

2011 ◽  
Vol 29 (12) ◽  
pp. 1531-1538 ◽  
Author(s):  
John M.S. Bartlett ◽  
Cassandra L. Brookes ◽  
Tammy Robson ◽  
Cornelis J.H. van de Velde ◽  
Lucinda J. Billingham ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Quantitative Analysis ◽  
Progesterone Receptor ◽  
Hormone Receptors ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Tamoxifen Treatment ◽  
Significant Information ◽  
Marker Effect ◽  
Er Positive

Purpose The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor–positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen. Patients and Methods Pathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment. Results Of 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgR- rich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P = .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P = .002), and multivariate analyses (P < .001 and P = .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. Conclusion Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment.

scholarly journals NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry

2009 ◽  
Vol 7 (Suppl_6) ◽  
pp. S-1-S-21 ◽  
Author(s):  
D. Craig Allred ◽  
Robert W. Carlson ◽  
Donald A. Berry ◽  
Harold J. Burstein ◽  
Stephen B. Edge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Invasive Breast Cancer ◽  
Hormone Receptors ◽  
Ductal Carcinoma ◽  
Task Force ◽  
Strong Predictor ◽  
Surgical Oncology ◽  
Task Force Report

The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.

scholarly journals Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

2013 ◽  
Vol 31 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Hatem A. Azim ◽  
Niels Kroman ◽  
Marianne Paesmans ◽  
Shari Gelber ◽  
Nicole Rotmensz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Pregnancy Outcome ◽  
Estrogen Receptor Status ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Er Positive ◽  
The Impact ◽  
Disease Free ◽  
Er Status

Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

scholarly journals Lost but Not Least—Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4755
Author(s):  
Michał Kunc ◽  
Marta Popęda ◽  
Wojciech Biernat ◽  
Elżbieta Senkus
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Neoadjuvant Treatment ◽  
Predictive Biomarkers ◽  
Immunohistochemical Analysis ◽  
Estrogen Receptor Α ◽  
Local Relapse ◽  
Copy Number Loss ◽  
Double Positive

Estrogen receptor α (ERα) and progesterone receptor (PgR) are crucial prognostic and predictive biomarkers that are usually co-expressed in breast cancer (BC). However, 12–24% of BCs present ERα(+)/PgR(−) phenotype at immunohistochemical evaluation. In fact, BC may either show primary PgR(−) status (in chemonaïve tumor sample), lose PgR expression during neoadjuvant treatment, or acquire PgR(−) phenotype in local relapse or metastasis. The loss of PgR expression in ERα(+) breast cancer may signify resistance to endocrine therapy and poorer outcomes. On the other hand, ERα(+)/PgR(−) BCs may have a better response to neoadjuvant chemotherapy than double-positive tumors. Loss of PgR expression may be a result of pre-transcriptional alterations (copy number loss, mutation, epigenetic modifications), decreased transcription of the PGR gene (e.g. by microRNAs), and post-translational modifications (e.g. phosphorylation, sumoylation). Various processes involved in the down-regulation of PgR have distinct consequences on the biology of cancer cells. Occasionally, negative PgR status detected by immunohistochemical analysis is paradoxically associated with enhanced transcriptional activity of PgR that might be inhibited by antiprogestin treatment. Identification of the mechanism of PgR loss in each patient seems challenging, yet it may provide important information on the biology of the tumor and predict its responsiveness to the therapy.

Overview of PROTACs targeting the estrogen receptor: Achievements for biological and drug discovery

2021 ◽  
Vol 28 ◽  
Author(s):  
Hui Qin ◽  
Yiwen Zhang ◽  
Yutao Lou ◽  
Zongfu Pan ◽  
Feifeng Song ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Hormone Receptors ◽  
Locally Advanced ◽  
Acquired Resistance ◽  
Endocrine Resistance ◽  
Steroid Hormone Receptors ◽  
Endocrine Diseases ◽  
Estrogen Receptor Modulators ◽  
Er Positive ◽  
Er Targeting

: Estrogen receptors (ERs) are steroid hormone receptors, which belong to a large nuclear receptor family. Endocrine diseases correlate strongly with dysregulated ER signaling. Traditional therapies continue to rely on small molecule inhibitors, including aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs), all of which permit acquired resistance to endocrine therapy. Proteolytic targeting chimeras (PROTACs) offer unprecedented potential for solving acquired endocrine resistance. ARV-471, an ER-targeting PROTAC developed by Arvinas, entered clinical trials in 2019 to treat patients suffering from locally advanced or metastatic ER-positive/HER2-negative breast cancer and has since been approved by the US FDA. In this review, we will focus on progress in developing ER-targeting PROTACs from publications and patents aimed at the treatment of endocrine diseases.

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

1990 ◽  
Vol 8 (8) ◽  
pp. 1310-1320 ◽  
Author(s):  
F Boccardo ◽  
A Rubagotti ◽  
P Bruzzi ◽  
M Cappellini ◽  
G Isola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Cancer Patients ◽  
Combined Treatment ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Er Positive ◽  
Positive Breast Cancer

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.

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