Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

NUMERICAL COEFFICIENT FOR ENDOMETRIAL CANCER INDIVIDUAL RISK EVALUATION IN POSTMENOPAUSAL WOMEN

2017 ◽  
Vol 63 (3) ◽  
pp. 461-465
Author(s):  
Lev Bershteyn ◽  
Dmitriy Vasilev ◽  
Tatyana Poroshina ◽  
Igor Berlev
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Risk Evaluation ◽  
Tumor Response ◽  
Molecular Genetic ◽  
Response To Treatment ◽  
Individual Risk ◽  
The Past ◽  
Genetic Landscape ◽  
Numerical Coefficient

Increased frequency of endometrial cancer (EC) since the beginning of this century exceeds that of breast cancer and to a large extent can be attributed to dynamics of parameters, which characterize hormonal and metabolic status of ill women and molecular genetic landscape of transforming endometrium. During the past few years there are suggested several options for a personalized assessment of the risk of EC. The aim of this article is to propose and justify own version of this score with the idea of its further not only retrospective but also prospective testing both in relation to the risk of developing endometrial cancer as well as an additional marker helping to predict tumor response to treatment.

scholarly journals Uterine serous carcinoma: key advances and novel treatment approaches

2021 ◽  
pp. ijgc-2021-002753
Author(s):  
J Stuart Ferriss ◽  
Britt K Erickson ◽  
Ie-Ming Shih ◽  
Amanda N Fader
Keyword(s):  
Endometrial Cancer ◽  
Black Women ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Serous Carcinoma ◽  
Cancer Syndrome ◽  
Her2 Positive ◽  
Incidence And Mortality ◽  
History Of ◽  
Uterine Serous Carcinoma

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast–ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

scholarly journals Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer

2012 ◽  
Vol 30 (6) ◽  
pp. 587-592 ◽  
Author(s):  
Eitan Amir ◽  
Naomi Miller ◽  
William Geddie ◽  
Orit Freedman ◽  
Farrah Kassam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Treatment Plan ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Primary Tumors ◽  
Receptor Status ◽  
Metastatic Recurrence ◽  
The Impact

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

scholarly journals Clinical, morphological, and molecular genetic predictors of metastatic lesions in the regional lymph nodes in breast cancer

2018 ◽  
Vol 5 (3) ◽  
pp. 8-16
Author(s):  
Yu. A. Dergunova ◽  
V. V. Podionov ◽  
V. K. Bozhenko ◽  
V. V. Kometova ◽  
M. V. Dardyk
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Molecular Genetic ◽  
Regional Lymph Nodes ◽  
Genetic Characteristics ◽  
Metastatic Lesions ◽  
Genetic Predictors ◽  
Node Metastases ◽  
High Degree

Despite the sufficient amount of data accumulated in the literature, there are still no factors, on the basis of which it would be possible to estimate the regional lymph nodes status in breast cancer with a high degree of accuracy. The review presents literature data relating to the influence of clinicopathological, molecular-biological and genetic characteristics of primary tumor on lymph node metastases. Data of 66 foreign and Russian articles are included.

The impact of estrogen receptor (ER), progesterone receptor (PR), and HER-2 receptor status on treatment of patients with advanced breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11580-e11580
Author(s):  
Paramjot Bains ◽  
Erin Diana Powell
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Her2 Status ◽  
Receptor Status ◽  
Original Tumour ◽  
Number Of Patients ◽  
Metastatic Sites ◽  
The Impact

e11580 Background: There are many variables that affect treatment options and outcomes in advanced breast cancer. The expression of ER, PR and HER2 are key in determining prognosis and management. The traditional management of breast cancer did not involve biopsy of metastatic sites. Recent studies indicate that, in a significant number of patients, there is a change in receptor status in the metastasis, and this may alter treatment. There have been many retrospective studies looking at the change in the ER/PR status of the metastatic site. Change in treatment as a result has been less of a focus. Our objective is to document the likelihood of a change in receptor status and the impact of this on treatment. Methods: This is a single center retrospective chart review. Ethics approval has been obtained through Memorial Univeristy of Newfoundland. The Dr. H. Bliss Murphy Cancer Centre database was used to identify 250 patients in Newfoundland who were diagnosed with metastatic breast cancer between January 2006 and November 2011. The review includes patients diagnosed with de novo metastases and those who developed metastases following adjuvant treatment. The information we are collecting includes ER, PR, and HER2 status of original tumour, whether metastases were biopsied and the results of the biopsy. We are also documenting all treatments administered. Results: The percentage of patients who underwent biopsy of metastases, the likelihood of change in receptor status and the likelihood of change in treatment will be calculated. Approximately half of the charts that met our criteria have been reviewed. Of those 125 patients, 35 had a biopsy specimen analyzed for ER/PR and HER2 status. 6 of these 35 patients had a change in their hormone receptor status, and 3 had a change in their HER2 status. The likelihood of change in treatment recommendations will be determined once all the data have been reviewed. These results will be available for the 2013 ASCO meeting. Conclusions: ER, PR and HER2 status may change from initial diagnosis of breast cancer to metastatic disease. This has important implications for treatment and prognosis, suggesting that biopsy of metastatic sites should be routine.

scholarly journals Hormone therapy after endometrial cancer.

2004 ◽  
Vol 11 (2) ◽  
pp. 305-314 ◽  
Author(s):  
A O Mueck ◽  
H Seeger
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Endometrial Carcinoma ◽  
Low Dose ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Increased Risk ◽  
Climacteric Complaints

Endometrial carcinoma is listed under the absolute contraindications to hormone therapy (HT). According to current opinion, HT after stage I or II is still considered an option, and continuous combined oestrogen/progestogen replacement therapy (CCEPT) would be recommended. However, up to now, only observational studies have been put forward. Although none of these studies have established an increased rate of recurrence or mortality, alternatives such as phytopreparations and tibolone, or particular psychotherapeutic drugs, such as venlafaxine, should be considered for the relief of climacteric complaints. Progestogen-only therapy (PT) particularly has been considered. However, the currently discussed possible progestogen effects regarding an increased risk of breast cancer have to be taken into account. Indeed, the wider discussion about the gestagen effects regarding the risk of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches or gels) instead of CCEPT, and this is also now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinoma, such as hypertension, obesity, polycystic ovary syndrome (PCO) and diabetes mellitus. However, each form of HT should be only exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.

scholarly journals Morphological and ultrasound characteristics of endometrium in patients with breast cancer and the risk of secondary tumors

2015 ◽  
Vol 6 (4) ◽  
pp. 39-47
Author(s):  
Aleksey V. Gerasimov ◽  
Sergey E. Krasilnikov ◽  
Anna G. Kedrova ◽  
Tatyana A. Maksimenko ◽  
Nataliya S. Afonina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Endometrial Hyperplasia ◽  
Breast Cancer Treatment ◽  
Tamoxifen Therapy ◽  
Histopathologic Examination ◽  
Second Cancer ◽  
Genetic Characteristics ◽  
Secondary Tumors ◽  
Adjuvant Tamoxifen Therapy

The analysis of features of endometrial hyperplasia in patients with breast cancer (BC) receiving adjuvant tamoxifen therapy in the period from 2011 to 2014 inclusive. 196 patients with breast cancer with ultrasound criteria of endometrial hyperplasia were examined. A postoperative histopathologic examination revealed that the lesions were endometrial hyperplasias and with 4,1% malignant findings. Hyperplasia, polyps and endometrial cancer were diagnosed in patients receiving tamoxifen, which allowed a comparison clinicoanamnestic, ultrasound, morphological and genetic characteristics of the endometrium to recover a high risk of developing a second cancer, as well as offer a pathogenic variant of its prevention. The article can be interesting as for obstetrician-gynecologist, watching women after breast cancer treatment, and oncologists, choosing a drug for adjuvant therapy.

Abstract P124: Network Meta-analysis of the Effects of Breast Cancer Hormone Therapy on Changes in Lipid Profiles

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Hsin-Hui Huang ◽  
Emma Barinas-Mitchell ◽  
Brenda Diergaarde ◽  
Chung-Chou Chang ◽  
Marnie Bertolet
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Randomized Clinical Trials ◽  
Early Stage ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Adjuvant Hormone Therapy ◽  
The Impact

Introduction: Adjuvant hormone therapy prolongs survival of patients with early-stage hormone receptor-positive breast cancer (BC). For postmenopausal patients, aromatase inhibitors (AIs) have been shown to improve disease free survival compared to tamoxifen, but the impact on overall survival has been inconsistent. A meta-analysis showed higher risk of cardiovascular diseases (CVDs) for patients taking AIs. Deteriorating lipids induced by AIs may contribute to this result. This analysis aims to compare the effects of hormone therapeutic options on changes in lipids from published randomized clinical trials (RCTs). Methods: RCTs evaluating effects of adjuvant hormone therapy on lipids (total cholesterol, high-density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), and/or triglycerides) in postmenopausal early-stage BC patients published in PubMed and Embase, prior to Jan. 31, 2016 were reviewed. Bayesian network meta-analysis was used to compare effects of placebo, selective estrogen receptor modulators (SERMs- tamoxifen and toremifene) and AIs (letrozole, anastrozole, and exemstane) on lipids across longitudinal time points. Heterogeneity was examined by meta-regressions adjusting for mean age, baseline lipid value, and prior tamoxifen use. An arm-based random effect model tested the consistency of the direct and indirect evidence of the drug effects. Results: We identified 17 articles from 13 RCTs for a total of 1,913 subjects. The Table summarizes the results, with statistically significant results bolded. Toremifene significantly improved all lipids and was the best choice regardless of covariate adjustment, while tamoxifen had weaker but significant LDLc lowering but opposite HDLc/triglyceride effects to toremifene. AIs generally had little effect on lipids. Conclusions: In general, AIs tend to have worse effects on lipids than SERMs, while only toremifene had beneficial effects on all lipid values. Patients on AIs with high risk of CVD should monitor their lipids.

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