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 Mahendra ◽  
Margareta Amelia ◽  
...  

Abstract PurposeTamoxifen, common adjuvant therapy prescribed in estrogen receptor positive (ER+) breast cancer, is metabolized by CYP2D6 enzyme into endoxifen. The phenotypes of CYP2D6, a highly polymorphic gene, vary from ultrarapid (UM), normal (NM), intermediate (IM), and poor metabolizers (PM). Studies showed that reduced CYP2D6 activity in IMs and PMs resulted in lower endoxifen level, thereby reducing therapy efficacy. This study aims to observe the distribution of CYP2D6 profiles and their corresponding endoxifen levels in Indonesian ER+ breast cancer patients.Methods151 patients who have received tamoxifen therapy for ≥8 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 metabolites measurement was performed using HPLC-tandem MS. Patients with IM/PM CYP2D6 profile were advised to increase their tamoxifen dose or switch to aromatase inhibitor, while patients with UM or NM CYP2D6 profile remained on 20 mg daily dose. Tamoxifen metabolites levels of those given 40 mg/day of tamoxifen were measured eight weeks post dose adjustment.ResultsWe found that 40.7% of patients recruited were IM. CYP2D6*10 was the most abundant allele (28.8%) and *10/*36 was the most frequently observed diplotype (23.6%). Endoxifen levels between the NM-PM, NM-IM, and IM-PM were statistically significant, and dose increase of tamoxifen successfully increased endoxifen levels in IMs to a similar level with NMs at baseline.ConclusionIndonesian women have a relatively high proportion of IMs. The correlation between CYP2D6 genotype and phenotype was shown in the significant difference in endoxifen levels among NMs, IMs, and PMs. Dose adjustment of tamoxifen to 40 mg daily positively increased endoxifen levels in IMs to a similar level as NMs. Implementing pharmacogenomics testing of CYP2D6 on ER+ breast cancer women taking tamoxifen can potentially increase the likelihood of achieving better treatment efficacy.Trial RegistrationThe trial was retrospectively registered at ClinicalTrials.gov on 18 March 2020 with identifier NCT04312347 (accessible at: https://clinicaltrials.gov/ct2/show/NCT04312347).

2018 ◽  
Vol 4 ◽  
pp. 3-13
Author(s):  
Yuriy Dumanskiy ◽  
Oleksandr Bondar ◽  
Oleksandr Tkachenko ◽  
Evhenii Stoliachuk ◽  
Vasilii Ermakov

In recent years, breast cancer (BC) is the most common cancer pathology and the most common cause of disability among women in developed countries. Finding the most effective ways of interaction between the patient and the doctor creates the preconditions for the necessary analysis of the treatment process from an objective and subjective point of view. Therefore, an important indicator to be taken into account is the quality of life of a patient. To compare the indicators of a comprehensive assessment of the quality of life of patients to the adverse locally advanced forms (LA) of breast cancer before and after systemic intravenous polychemotherapy (SPCTx) and selective endolymphatic polychemotherapy (ELPCTx) in neoadjuvant mode. The study was conducted on the basis of a random analysis of outpatient cards from 112 patients with LA BC T4A-DN0-3M0 who received a comprehensive antitumor treatment on the basis of the Donetsk regional antitumor center and the University Clinic of the Odessa National Medical University from 2000 to 2017, which was proposed a questionnaire at various stages of preoperative treatment. The first (control) group consisted of 65 patients (58 %) with inoperable forms of LA BC, which was performed in neoadjuvant mode by SPCTx. The second (study group) included 47 patients (42 %) with inoperable forms of LA BC, which was performed as a neoadjuvant course ELPCTx. According to the integral indicators of quality of life and quality of health between patients in the control and study groups, there was no statistically significant difference. In a detailed analysis of the indicators of symptomatic scales, the difference between the groups did not exceed the critical. Based on the results of a study conducted among patients receiving endolymphatic chemotherapy in a neoadjuvant mode, the subjective evaluations of treatment in absolute numbers have better reference values without statistical superiority. The study of the integrative indicator of quality of life and its discrete elements is an ergonomic and economical means of heuristic assessment of the health of patients in order to further develop more rational and convenient ways of solving urgent issues of modern oncology by increasing compliance and finding a compromise between the physician and the patient.


2020 ◽  
Vol 27 (37) ◽  
pp. 6373-6383 ◽  
Author(s):  
Leila Jouybari ◽  
Faezeh Kiani ◽  
Farhad Islami ◽  
Akram Sanagoo ◽  
Fatemeh Sayehmiri ◽  
...  

: Breast cancer is the most common neoplasm, comprising 16% of all women's cancers worldwide. Research of Copper (Cu) concentrations in various body specimens have suggested an association between Cu levels and breast cancer risks. This systematic review and meta-analysis summarize the results of published studies and examine this association. We searched the databases PubMed, Scopus, Web of Science, and Google Scholar and the reference lists of relevant publications. The Standardized Mean Differences (SMDs) between Cu levels in cancer cases and controls and corresponding Confidence Intervals (CIs), as well as I2 statistics, were calculated to examine heterogeneity. Following the specimens used in the original studies, the Cu concentrations were examined in three subgroups: serum or plasma, breast tissue, and scalp hair. We identified 1711 relevant studies published from 1984 to 2017. There was no statistically significant difference between breast cancer cases and controls for Cu levels assayed in any studied specimen; the SMD (95% CI) was -0.01 (-1.06 - 1.03; P = 0.98) for blood or serum, 0.51 (-0.70 - 1.73; P = 0.41) for breast tissue, and -0.88 (-3.42 - 1.65; P = 0.50) for hair samples. However, the heterogeneity between studies was very high (P < 0.001) in all subgroups. We did not find evidence for publication bias (P = 0.91). The results of this meta-analysis do not support an association between Cu levels and breast cancer. However, due to high heterogeneity in the results of original studies, this conclusion needs to be confirmed by well-designed prospective studies.


2020 ◽  
Vol 16 (2) ◽  
pp. 152-159
Author(s):  
Arezoo Shayan ◽  
Mansoureh Refaei ◽  
Farkhondeh Jamshidi

Background: Treatment of breast cancer can be accompanied by long-term consequences affecting women’s participation in many tasks. Objective: This study aimed to assess the effect of cognitive behavioral stress management (CBSM) program on occupational performance of women with breast cancer. Methods: In this randomized clinical trial, conducted between Feb 3 and Oct 26, 2016, 104 women with breast cancer who had referred to Imam Khomeini clinic in Hamadan, and who fulfilled the inclusion criteria (20-60 years old, married, suffering from grade 1-3 breast cancer with a history of recent surgery) were enrolled. They were randomly divided into two groups of 52 using a permuted block size of four. The intervention group took part in four 60-minute sessions of CBSM over four weeks. The study data were collected using a demographic information form and the Canadian Occupational Performance Measure. The statistical analyst was masked to intervention allocation. The data were analyzed using descriptive statistics, paired t-test, and repeated measures ANOVA. Results: A significant difference was observed between the two groups regarding the mean scores of occupational performance (p=0.02) and satisfaction (p=0.005) after the intervention. Each variable was measured at three time points (before the intervention, immediately and 2 weeks after intervention). A significant difference was observed in the two groups’ mean scores of performance (p=0.026) and satisfaction (p=0.01), irrespective of the time of assessment. Conclusion: The CBSM program promoted the occupational performance immediately and two weeks after the intervention in women with breast cancer. This technique can be used as a complementary method alongside medical therapies in oncology centers.


Author(s):  
Ozlem Demircioglu ◽  
Huseyin Tepetam ◽  
Ayfer Ay Eren ◽  
Zerrin Ozgen ◽  
Fatih Demircioglu ◽  
...  

Background: Accurate localization of the lumpectomy cavity is important for breast cancer radiotherapy after breast-conserving surgery (BCS), but the LC localization based on CT is often difficult to delineate accurately. The study aimed to compare CT-defined LC planning to MRI-defined findings in the supine position for higher soft-tissue resolution of MRI. Methods: Fifty-nine breast cancer patients underwent radiotherapy CT planning in supine position followed by MR imaging on the same day. LC was contoured by the radiologist and radiation oncologist together by CT and MRI separately. T2 weighted MR images and tomography findings were combined and the LC volume, mean diameter and the longest axis length were measured after contouring. Subsequently, patients were divided into two groups according to seroma in LC and the above-mentioned parameters were compared. Results: We did not find any statistically significant difference in the LC volume, mean diameter and length at the longest axis between CT and MRI but based on the presence or absence of seroma, statistically significant differences were found in the LC volumes and the length at the longest axis of LC volumes. Conclusion: We believe that the supine MRI in the same position with CT will be more effective for radiotherapy planning, particularly in patients without a seroma in the surgical cavity.


Sign in / Sign up

Export Citation Format

Share Document