scholarly journals Preliminary Pharmacogenomic-Based Predictive Models of Tamoxifen Response in Hormone-dependent Chilean Breast Cancer Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Carla Miranda ◽  
Macarena Galleguillos ◽  
Roberto Torres ◽  
Karla Tardón ◽  
Dante D. Cáceres ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Polymorphisms ◽  
Predictive Models ◽  
Genetic Variants ◽  
Vaginal Bleeding ◽  
Oestrogen Receptor ◽  
Endometrial Hyperplasia ◽  
Metastatic Breast ◽  
Individual Response ◽  
Clinical Records

Tamoxifen (TAM), a selective oestrogen receptor modulator, is one of the most used treatments in oestrogen receptor-positive (ER+) early and metastatic breast cancer (BC) patients. The response to TAM has a high degree of inter-individual variability. This is mainly due to genetic variants in CYP2D6 gene, as well as other genes encoding proteins involved in the TAM pharmacokinetic and/or pharmacodynamic. Therefore, prediction of the TAM response using these genetic factors together with other non-genetic variables may be relevant to improve breast cancer treatment. Thus, in this work, we used genetic polymorphisms and clinical variables for TAM response modelling. One hundred sixty-two ER + BC patients with 2 years of TAM treatment were retrospectively recruited, and the genetic polymorphisms CYP2D6*4, CYP3A4*1B (CYP3A4*1.001), CYP3A5*3, UGT2B7*2, UGT2B15*2, SULT1A1*2, and ESRA V364E were analyzed by PCR-RFLP. Concomitantly, the therapeutic response was obtained from clinical records for association with genotypes using univariate and multivariate biostatistical models. Our results show that UGT2B15*1/*2 genotype protects against relapse (OR = 0.09; p = 0.02), CYP3A5*3/*3 genotype avoids endometrial hyperplasia (OR = 0.07; p = 0.01), SULT1A1*1/*2 genotype avoids vaginal bleeding (OR = 0.09; p = 0.03) and ESRA 364E/364E genotype increases the probability of vaginal bleeding (OR = 5.68; p = 0.02). Logistic regression models, including genomic and non-genomic variables, allowed us to obtain preliminary predictive models to explain relapse (p = 0.010), endometrial hyperplasia (p = 0.002) and vaginal bleeding (p = 0.014). Our results suggest that the response to TAM treatment in ER + BC patients might be associated with the presence of the studied genetic variants in UGT2B15, CYP3A5, SULT1A1 and ESRA genes. After clinical validation protocols, these models might be used to help to predict a percentage of BC relapse and adverse reactions, improving the individual response to TAM-based treatment.

Sinophobic Growth in Oestrogen Receptor-Negative Metastatic Breast Cancer

Oncology ◽  
1983 ◽  
Vol 40 (4) ◽  
pp. 241-243 ◽  
Author(s):  
F. Hartveit ◽  
T. Thorsen ◽  
M. Tangen ◽  
B.O. Mœhle ◽  
S. Thoresen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Oestrogen Receptor ◽  
Metastatic Breast

scholarly journals GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (62) ◽  
pp. 105905-105914 ◽  
Author(s):  
Jian Zhang ◽  
Ying Wu ◽  
Xichun Hu ◽  
Biyun Wang ◽  
Leiping Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Variants ◽  
Metastatic Breast

scholarly journals Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding During Chemotherapy: A Case Report and Literature Review

Chirurgia ◽  
2018 ◽  
Vol 113 (4) ◽  
pp. 564 ◽  
Author(s):  
A Saad Abdalla Al-Zawi ◽  
Anita Lazarevska ◽  
Mohammed Murwan Omer ◽  
Elizabeth Tan ◽  
Amira Asaad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Case Report ◽  
Literature Review ◽  
Vaginal Bleeding ◽  
Metastatic Breast ◽  
Abnormal Vaginal Bleeding

Therapeutic Place of Fulvestrant in the Management of Hormone-receptor Positive Breast Cancer

2016 ◽  
Vol 12 (01) ◽  
pp. 44 ◽  
Author(s):  
Yogesh R Belagali ◽  
Hanmant V Barkate ◽  
Jaykumar J Sejpal ◽  
Bhavesh B Parekh ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Oestrogen Receptor ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
First Line Therapy ◽  
Hormone Receptor Positive ◽  
Significant Difference ◽  
Turnover Markers ◽  
Positive Breast Cancer

Fulvestrant is an oestrogen-receptor antagonist that exerts selective oestrogen receptor downregulation, antiproliferative activity and induction of apoptosis. It is indicated for the treatment of postmenopausal women with locally advanced or metastatic breast cancer for disease relapse or progression on or after adjuvant anti-oestrogen therapy. Fulvestrant was initially approved at a dose of 250 mg, however, the results of the CONFIRM trial led to approval of 500 mg dose (i.e. 500 mg on days 0, 14 and 28, then 500 mg every 28 days). Fulvestrant has also shown superiority over anastrozole as first-line therapy in the phase II trial. There are contrasting data for its efficacy when used in combination with anastrozole. It is well tolerated, with no significant difference with respect to the toxicity profile of other hormonal therapies. Treatment with fulvestrant is not associated with any clinically significant effects on sex hormone levels, bone-specific turnover markers or endometrial thickening. Fulvestrant has been recommended by the National Comprehensive Cancer Network and the European School of Oncology guidelines as a treatment option in first- and second-line management of hormone-receptor positive breast cancer.

scholarly journals β2-Adrenergic Signalling Promotes Cell Migration by Upregulating Expression of the Metastasis-Associated Molecule LYPD3

Biology ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 39 ◽  
Author(s):  
Michael Gruet ◽  
Daniel Cotton ◽  
Clare Coveney ◽  
David J. Boocock ◽  
Sarah Wagner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Drug Targets ◽  
Oestrogen Receptor ◽  
Beta Blockers ◽  
Metastatic Breast ◽  
Breast Tumour ◽  
Protein Profiling ◽  
Basal Type

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line models of basal-type and oestrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and β2-adrenoceptor mediated cell behaviour including migration, invasion, adhesion, and survival in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified biomarkers and drug targets. Baseline levels of adrenoceptor gene expression are higher in basal-type rather than oestrogen receptor-positive cancer cells. Norepinephrine (NE) treatment increased invasive capacity in all cell lines but did not increase proliferation/survival. Protein profiling revealed the upregulation of the pro-metastatic gene Ly6/PLAUR Domain-Containing Protein 3 (LYPD3) in norepinephrine-treated MDA-MB-468 cells. Histology confirmed selective LYPD3 expression in primary and metastatic breast tumour samples. These findings demonstrate that basal-type cancer cells show a more aggressive adrenoceptor-β2-activated phenotype in the resting and stimulated state, which is attenuated by adrenoceptor-β2 inhibition. This study also highlights the first association between ADRβ2 signalling and LYPD3; its knockdown significantly reduced the basal and norepinephrine-induced activity of MCF-7 cells in vitro. The regulation of ADRβ2 signalling by LYPD3 and its metastasis promoting activities, reveal LYPD3 as a promising therapeutic target in the treatment of breast and other cancers.

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