Common polymorphisms in the estrogen receptor-1 may determine risk of hot flashes in early breast cancer patients using tamoxifen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 526-526
Author(s):  
Vincent O. Dezentje ◽  
Henk-jan Guchelaar ◽  
Ron H. N. van Schaik ◽  
Judith M. Vletter - Bogaartz ◽  
Tahar van der Straaten ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Hot Flashes ◽  
Tamoxifen Treatment ◽  
First Year ◽  
Breast Cancer Patients ◽  
Estrogen Receptor 1

526 Background: In breast cancer patients the occurrence of hot flashes as common side effect of tamoxifen therapy may be associated with effective estrogen receptor antagonism dependent on genetic variations of metabolic enzymes and the estrogen receptor. Methods: 742 early breast cancer patients who were randomized to receive tamoxifen, followed by exemestane after 2.5 to 3 years within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial were genotyped for 30 germ line genetic variants of 11 enzymes that are involved in the tamoxifen metabolism and the estrogen receptor 1 (ESR1). These genetic variants were related to the occurrence of hot flashes during the first year of tamoxifen use (primary aim) and during the complete tamoxifen treatment period (secondary aim). A multivariable logistic regression was used to adjust for age and adjuvant chemotherapy. Results: No genetic variant was associated with the occurrence of hot flashes during the first year. Higher age was related to a lower incidence of hot flashes in the first year (adjusted odds ratio 0.94, 95% CI 0.92-0.96; p<0.001). The ESR1 PvuII XbaI CG haplotype (CG/CG vs CG/other + other/other: adjusted odds ratio 0.44, 95% CI 0.21-0.92; p=0.03), ESR1 PvuII XbaI TA haplotype (TA/TA + TA/other vs other/other: adjusted odds ratio 1.86, 95% CI 1.09-3.14; p=0.02) and age (adjusted odds ratio 0.94, 95% CI 0.92-0.97; p<0.001) were associated with the occurrence of hot flashes during the total tamoxifen treatment period. No association was found between the CYP2D6 predicted phenotype and hot flashes. Conclusions: Common polymorphisms in the estrogen receptor-1 might help to predict the occurrence of hot flashes in breast cancer patients treated with adjuvant tamoxifen. If replicated, this may provide clinicians with a tool to offer more personalized hormonal therapy.

Clinical significance of estrogen receptor 1 gene mutations in hormonal resistant breast cancer patients

Gene Reports ◽  
2021 ◽  
pp. 101261
Author(s):  
Reham A. Aboelwafa ◽  
Nermine H. Zakaria ◽  
Neamat Hagazy ◽  
Inas I. Zaki ◽  
Aya S. Rady ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Gene Mutations ◽  
Breast Cancer Patients ◽  
Estrogen Receptor 1

Association of the phosphorylation of the estrogen receptor at serine 118 and 167 with prognosis in postmenopausal breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 562-562
Author(s):  
Karin J. Beelen ◽  
Mark Opdam ◽  
Rutger H.T. Koornstra ◽  
Andrew D. Vincent ◽  
Jan Baptist Vermorken ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Therapy ◽  
Postmenopausal Breast Cancer ◽  
Tamoxifen Treatment ◽  
Adjuvant Tamoxifen ◽  
Breast Cancer Patients ◽  
Premenopausal Breast Cancer ◽  
Cox Models

562 Background: The sensitivity of the estrogen receptor (ERα) to anti-estrogen therapy can be affected by phosphorylation events. In premenopausal breast cancer patients, phosphorylation of the ERα at serine 118 (ERαS118-p) is predictive for benefit from adjuvant tamoxifen. Since ERαS118-p represents the common hallmark of different signaling cascades that differ in E2 dependency, the resulting effect on estrogen sensitivity may differ between pre- and postmenopausal patients. Phosphorylation of serine 167 (ERαS167-p) has been associated with favorable disease outcome, but whether ERαS167-p can predict tamoxifen sensitivity is currently unknown. We tested the predictive value of both ERαS118-p and ERαS167-p for benefit from adjuvant tamoxifen in postmenopausal breast cancer patients. Methods: We collected primary tumor blocks from 563 ERα positive (stage I-III) postmenopausal patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial). The median follow-up of patients without a recurrence event was 9.4 years. Immunohistochemistry was performed on a TMA using monoclonal antibodies for ERαS118-p and ERαS167-p. The percentage of positive nuclei was scored and a score of ≥ 10 % was considered as positive. Multivariate Cox models were used to assess hazard ratios (HRs) for recurrence free interval and the interaction between these phosphorylations and tamoxifen treatment. Results: We did not find a significant interaction between either ERαS118-p (p=0.99) or ERαS167-p (p=0.44) and tamoxifen, suggesting that the relative benefit from adjuvant tamoxifen in postmenopausal patients is not dependent on the presence of one of these phosphorylations. Both tamoxifen treated patients as well as control patients had a better prognosis when their tumor was positive for ERαS118-p (adjusted HR 0.60 p=0.02) or ERαS167-p (adjusted HR 0.62, p=0.02) compared to patients whose tumor did not express these ERα phosphorylations. Conclusions: In postmenopausal patients ERαS118-p and ERαS167-p are both associated with better prognosis, but do not predict differential benefit from tamoxifen.

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.

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

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