scholarly journals CYP2D6 Genotyping for Personalized Therapy of Tamoxifen in Indonesian Women with ER+ Breast Cancer

Author(s):  
Baitha Palanggatan Maggadani ◽  
Kathleen Irena Junusmin ◽  
Levana L. Sani ◽  
Caroline Irena Mahendra ◽  
Margareta Amelia ◽  
...  

Tamoxifen is a Selective Estrogen-Receptor Modulator (SERM) commonly prescribed for standard of care in estrogen receptor positive (ER+) breast cancer as an adjuvant therapy. Tamoxifen is metabolized by CYP2D6 into its active metabolite, endoxifen, which has been known to play an important role in reducing risk of ER+ breast cancer recurrence. CYP2D6 is a highly polymorphic gene with more than 100 alleles. The phenotype of this gene is categorized into ultrarapid metabolizer (UM), normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM). Certain CYP2D6 polymorphisms may cause reduced activity of this enzyme. Studies have found that reduced CYP2D6 activity in IM and PM patients causes low efficacy of standard tamoxifen therapy. This study aims to observe the distribution of CYP2D6 alleles and its correlation with endoxifen levels in Indonesian ER+ breast cancer patients. 151 patients who have received tamoxifen therapy for at least eight weeks were recruited prospectively. DNA and blood samples were collected with buccal swab and finger-prick methods, respectively. Genotyping was performed using the qPCR method while metabolite level measurement was performed using high performance liquid chromatography tandem mass spectrometry. We found that 40.67% of ER+ breast cancer patients recruited were IM. CYP2D6*10 was the most abundant allele (0.288) in this population, and *10/*36 was the most frequently observed diplotype (0.236). Endoxifen levels between the NM-PM, NM-IM, and IM-PM were statistically significant (p-value = 6.26 x 10-5, 9.12 x 10-5, and 4.714 x 10-3, respectively), and dose increase of tamoxifen to 40 mg daily successfully increased endoxifen levels in IMs to a similar level with NMs at baseline. Given these findings, implementing pharmacogenomic testing of CYP2D6 on ER+ breast cancer women who are about to undergo tamoxifen therapy may be beneficial to increase the likelihood of achieving expected endoxifen levels, thus better treatment efficacy.

2020 ◽  
Vol 13 (1) ◽  
pp. 30-35
Author(s):  
Leyli Hosseini ◽  
Mehdi Dehghani ◽  
Sedigheh Tahmasebi ◽  
Majid Akrami ◽  
Nasrin Shokrpour ◽  
...  

Background: Breast cancer is the most prominent cause of women's mortality due to cancer and is one of the most serious and commonly diagnosed cancers among Iranian women. Also, social support plays a vital role in breast cancer patients' lives and their diagnosis and treatment processes. This study aimed to determine the associations between social support status and the recurrence of breast cancer in women breast cancer referred to the Breast Diseases Research Center in Motahari Clinic in Shiraz, Iran in 2018. Methods: This was an applied and descriptive-analytic study on women with breast cancer referred to the Breast Diseases Research Center in Motahari Clinic in Shiraz, Iran in 2018. A sample of 221 patients in two groups of 117 non-recurrence patients and 44 patients with recurrence and metastasis were selected randomly. A localized standard questionnaire was used to collect the required data. The collected data were analyzed using SPSS 24.0. Results: Based on the results, there were significant differences between the two studied groups of patients with and without recurrence in terms of the means of social support and all of its dimensions (P-value<0.05); the means of social support and all of its dimensions in the group of patients without recurrence were higher than those in those with recurrence. Also, 88.6% of patients in the group without recurrence received high social support, while in the group of patients with recurrence, only 11.4% of them received high social support. Conclusion: The results showed that the breast cancer patients studied without recurrence had higher social support. Therefore, to improve the studied patients' health, we recommend providing the patients with a safe and secure environment, giving accurate and complete responses to the patients' questions, providing continuous psychological counseling, etc.


2020 ◽  
Vol 6 (1) ◽  
pp. 1-4
Author(s):  
Jumikha Tamara Sahmaulyana Sidauruk

Background: Breast cancer is a malignancy in breast tissue that can be originated from ductal epithelium and lobules. It is the main cause of death from cancer suffered by women in the world. Age and hormonal are important risk factors for breast cancer where the longer a person is exposed to estrogen, the higher is the risk for breast cancer. The estrogen receptor is one of the main prognostic and predictive factors examined in breast cancer and can be determinant for hormonal therapy. Objectives: This study aimed to discover the relation between age and estrogen receptor in breast cancer patients of RSUD Dr.Pirngadi Medan in 2018. Methods: This research was an analytical study with a cross-sectional design. The research sample was 96 breast cancer patients by medical records of RSUD Dr.Pirngadi Medan in 2018 collected by a consecutive sampling method. Analysis of the data in this study was done by univariate to describe the characteristics of research subjects, while bivariate analysis used the chi-square test method to analyze the relationship between age and estrogen receptor. Results: The patients with breast cancer in RSUD Dr.Pirngadi Medan 2018 was mostly >40 years old (79.2%), with negative estrogen receptor hormonal status (53%), status was married (99%), and the highest level of education was high school (54.2%). The results of the study showed that there was a relationship between age and estrogen receptor in breast cancer patients with p-value =0.007 (p value<0,05). Conclusion: There was a significant relationship between age and estrogen receptors and estrogen receptors in breast cancer patients in RSUD Dr.Pirngadi Medan 2018.


2021 ◽  
pp. 1-5
Author(s):  
David Samuel Kereh ◽  
John Pieter ◽  
William Hamdani ◽  
Haryasena Haryasena ◽  
Daniel Sampepajung ◽  
...  

BACKGROUND: AGR2 expression is associated with luminal breast cancer. Overexpression of AGR2 is a predictor of poor prognosis. Several studies have found correlations between AGR2 in disseminated tumor cells (DTCs) in breast cancer patients. OBJECTIVE: This study aims to determine the correlation between anterior Gradient2 (AGR2) expression with the incidence of distant metastases in luminal breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and the network. ELISA methods examine AGR2 expression from blood serum of breast cancer patients. To compare the AGR2 expression in metastatic patients and the non-metastatic patient was tested with Mann Whitney test. The correlation of AGR2 expression and metastasis was tested with the Rank Spearman test. RESULTS: The mean value of AGR2 antibody expression on ELISA in this study was 2.90 ± 1.82 ng/dl, and its cut-off point was 2.1 ng/dl. Based on this cut-off point value, 14 subjects (66.7%) had overexpression of AGR2 serum ELISA, and 7 subjects (33.3%) had not. The mean value AGR2 was significantly higher in metastatic than not metastatic, 3.77 versus 1.76 (p < 0.01). The Spearman rank test obtained a p-value for the 2 tail test of 0.003 (p < 0.05), which showed a significant correlation of both, while the correlation coefficient of 0.612 showed a strong positive correlation of AGR2 overexpression and metastasis. CONCLUSIONS: AGR2 expression is correlated with metastasis in Luminal breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 147
Author(s):  
Leticia Díaz-Beltrán ◽  
Carmen González-Olmedo ◽  
Natalia Luque-Caro ◽  
Caridad Díaz ◽  
Ariadna Martín-Blázquez ◽  
...  

Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.


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