ROLE OF DNA METHYLATION AS A DIAGNOSTIC BIOMARKER OF SPORADIC BREAST CANCER

The initiation and progression of breast cancer have been recognized for many years to be secondary to the accumulation of genetic mutations which lead to aberrant cellular function. Genetic mutations, either inherited or sporadic, may result in the activation of oncogenes and the inactivation of tumor suppressor genes. The more recent discovery that reversible alterations in histone proteins and deoxyribonucleic acid (DNA) can also lead to tumorigenesis has introduced a novel term to the field of cancer research: epigenetics.  Epigenetics refers to the study of heritable changes in gene regulation that do not involve a change in the DNA sequence. The most often studied in epigenetics of breast cancer is DNA methylation. That a promoter methylation result in transcription blockade supports the notion that cellular inhibition takes place. Compared to normal tissues, hypermethylation occurs from double to triple in cancerous ones. DNA methylation plays a crucial role in oncogenesis and is one of the hallmarks of cancer.Detection of aberrantly methylated CpG islands in promoter region of several genes in DNA sample derived from nipple aspirates, serum, or cancer tissue associated with down regulation of expression or loss of function of these genes has been associated with early stages of breast cancer, where  hypermethylation of CpG island points to poorer prognosis in breast cancer.  DNA methylation has been identified as signature for TNBC. Methylation of BRCA1 gene is frequently demonstrated in young, estrogen receptor-negative breast cancer patients. Methylation of specific genes is known to differ across race and socioeconomic status. BRCA1 methylation in premenopausal women with sporadic breast cancer in West Sumatra region has been higher than in Western women.DNA methylation may be used to enhance current breast cancer classification. There is such a distinction between methylation and gene expression profiles of breast cancer that not all methylation profiles fit within the same molecular subtype. Specific gene methylation profiles are identified for basal-like, luminal A and HER2-overexpressing breast cancers. A number of studies have analyzed the methylation status of BRCA1, a key player in TNBC. One study demonstrated that BRCA1 promoter was methylated in TNBC.  It was discovered that the sensitivity of TNBC cell lines to PARP inhibitors was increased when BRCA1 was methylated. Concurrently, BRCA1 methylation quantity was higher in patients with complete response than in those who are non-responders of neoadjuvant chemotherapy.Epigenetics is now the cutting edge of cancer research.  Advances in this field will have major implications in diagnosis, prevention, treatment of cancer, and formulation of new epigenetically targeted cancer drugs

Pembedahan Pada Tumor Ganas Payudara

Pembedahan Pada Tumor Ganas Payudar

Peranan microRNA dalam diagnosis dan tata laksana kanker payudara

Epigenetik adalah suatu perubahan ekspresi gen yang dapat diturunkan namun tidak terdapat perubahan sekuen DNA pada gen tersebut. Saat ini diperlukan adanya identifikasi proses epigenetik peranan microRNA dalam diagnosis dan tatalaksana kanker payudara. Tujuan: Penelitian ini bertujuan untuk mengidentifikasi peran microRNA (miRNA) dalam diagnosis dan tatalaksana kanker payudara. Metode: Penelitian ini merupakan literature review terhadap artikel penelitian yang terpublikasi secara internasional pada database Pubmed/Medline dan Proquest dari tahun 1998-2019. Studi literatur ini disusun berdasarkan panduan Walker dan Avant. Hasil: Peranan miRNA yang dapat menginduksi dan dapat juga mencegah kanker serta peranannya dalam tingkat agresivitas kanker menjadikan mikro molekul dapat dijadikan biomarker untuk deteksi dini dan penilaian agresivitas kanker payudara (KPD). Lepasnya miRNA dari tumor ke dalam sirkulasi darah dapat dijadikan indikator biomarker baik sebagai diagnostik, prognostik, dan prediktif. level ekspresi miRNA juga dapat dijadikan monitor terhadap status tumor, sehingga menjadi catatan penting bahwa pengangkatan primer tumor akan mengurasi jumlah miRNA yang bersirkulasi di dalam darah. Simpulan: miRNA dapat digunakan baik sebagai biomarker pada KPD dan juga sebagai bagian dari terapi KPD

Hubungan Aktivitas Fisik Harian dengan Kualitas Hidup Penyintas Kanker Payudara

This study aims to determine the relationship of daily physical activity with the quality of life of breast cancer survivors. The research design used is correlative with a cross-sectional approach. The results showed 53.9% of respondents aged > 60 years, 50.6% of respondents had higher education, 61.8% of respondents did not work, 49.1% of stage IIIA respondents, 55.1% of respondents had moderate daily physical activity, and 73,0% of respondents have a reasonable quality of life. Most respondents have moderate physical activity, 55.1%, with most of the quality of life being 73.0%. The results of the bivariate analysis showed that (p-value = 0.034). In conclusion, there is a relationship between daily physical activity and the quality of life of breast cancer survivors at RSUP Dr. M. Djamil Padang.   Keywords: Physical Activity, Breast Cancer, Quality of Lif

Improved PCR-RFLP Method For Her-2 Ile655val Breast Cancer Patients Detection

HER2 is a protein that is essential to the process of differentiation, proliferation, tissue development and other physiological processes. HER-2 overexpression was occurred in 20-30% of breast cancer patients. Targeted therapies was performed using trastuzumab, on the basis of the examination by immunohistochemistry. Single nucleotide polimorphisme (SNP) Ile655Val were found on HER-2, which indicates the risk of cancer as well as a predictive factor of treatment with targeted therapies. The method had been used for HER-2 SNP detection is using TaqMan method which is expensive, or PCR RFLP which is cheaper and easier. 148bp PCR product was widely used in PCR RFLP for HER-2 Ile655Val SNP detection confirmed at high concentration of agarose  (3%). This study conducted to improve the PCR RFLP methods become more economical and more efficient by increasing the size of the PCR products confirmed with low concentration of agarose which have lower prices. The results showed that PCR RFLP method developed in this study, 480bp PCR product restricted with BsmAI  confirmed with 2% agarose,  has been successfully performed with more economist and a high level of reproducibility

Pemeriksaan Payudara Sendiri (SADARI) dengan Stadium Kanker Payudara

This study aims to determine the relationship between breast self-examination (BSE) and the stage of breast cancer at RSUP Dr. M. Djamil Padang in 2020. The method used is a mixed-method with a Sequential Explanatory Design. Sampling technique using Consecutive Sampling. Quantitative data was obtained through questionnaires and qualitative data using interviews. The results showed that the number of respondents who were not good at breast self-examination (BSE) was 64 (58.2%) and respondents who were good at breast self-examination (BSE) were 46 (41.6%). The most common breast cancer stages were at stage 3 of 67 (63.9%), stage 2 of 30 (27.3%) and the least at stage 4 was 13 (11.8%) with a p-value = 0.020. In conclusion, there is a relationship between breast self-examination (BSE) and the stage of breast cancer. Keywords: Breast Self-Examination (BSE), Breast Cancer Stag

Breasts and Lymphatic Tissue ; A Literature Review

The breasts begin to grow from the sixth week of the embryo in the form of ectodermal thickening along the milk line that lies from the axilla to the middle of the groin (inguinal). The blood supply comes from the internal mammary artery, which is a branch of A. subclavian. Additional bleeding originated from A. axillary through the branches of A. thoracic lateral, A. thoraco dorsalis, and A. thoraco acromialis. The return of blood through the veins follows the passage of the artery to the internal mammary V. and the axillary vein branches to the superior V. kava. Lymph capillaries are located under the epidermis with a diameter between 20 and 70 mm. Lymphangion, as a pacemaker is limited by valves and lymphatic endothelial cells, will initiate an intrinsic pulsation of lymph fluid flow. Extrinsic factors such as contraction of the skeletal muscles, massage, increased hydrostatic pressure by postural gravity can also affect the lymphatic flow rate.5,6 These lymphatic vessels run on the lateral side of the upper arm, parallel to the cephalic vein and drain into the supraclavicular nodes. 4 The LVC is an important anatomical structure for the physiology of vascular lymph node transplantation (VLNT) .8 Lymph vessels in the upper limb travel axially from the fingers to the back of the hand and make direction to the elbow, travel to the anteromedial area at the top of the arm and connect to the axillary lymph nodes in the lateral area. An alternative route directly to the supraclavicular node can be identified. These lymphatic vessels run on the lateral side of the upper arm, parallel to the cephalic veins and drain into the supraclavicular nodes. 4 The LVC is an important anatomical structure for the physiology of vascular lymph node transplantation (VLNT) .8An alternative route directly to the supraclavicular node can be identified. These lymphatic vessels run on the lateral side of the upper arm, parallel to the cephalic veins and drain into the supraclavicular nodes. 4 An alternative route directly to the supraclavicular node can be identified. These lymphatic vessels run on the lateral side of the upper arm, parallel to the cephalic veins and drain into the supraclavicular nodes

Prognostic Factors of Local-Regional Recurrence in Patients with Operable Breast Cancer in Asia: A Meta-Analysis: Prognostic factors for local regional recurrence in operable breast cancer patients in Asia

BACKGROUND: Cause of recurrence of breast cancer is multifactorial. Also, the occurrence of breast cancer in Asian patients has some different factors from the recurrence of breast cancer in western countries. AIM: This study aims to determine the prognostic factors of local-regional recurrence in patients with operable breast cancer in Asia. METHODS: The authors conducted a meta-analysis of published research articles published in an online database of PubMed, ProQuest and EBSCO between January 2000 and July 2018. Pooled risk ratios (RR) were calculated using fixed and random-effect models. Data were processed by using Review Manager 5.3 (RevMan 5.3). RESULTS: This study reviewed 879 articles. There were 11 studies conducted a systematic review then continued by meta-analysis of relevant data with total patients involved were 5,213 patients. The prognostic factors found of local-regional recurrence in patients with operable breast cancer were Nodal (N) stage with the highest risk ratio (RR = 6.35 [95% CI 3.78-10.67]) followed by HER2 positive (RR = 2.14 [95% CI 1.16-3.97]), stage of cancer (RR = 1.82 [95% CI 1.44-2.31]), tumor size (RR = 1.55 [95% CI 1.04-2.31]), tumor grade (RR = 1.43 [95% CI 1.23-1.65]), PR status (RR = 0.65 [95% CI 0.48-0.88]) and the least was ER status (RR = 0.60 [95% CI 0.39-0.91]). Homogeneity of variance was found in N stage, tumor size and tumor grade for recurrence of operable breast cancer. CONCLUSION: This meta-analysis confirmed the correlation of N stage, HER2, stage of cancer, tumour size, tumour grade, ER and PR status with recurrence in patients with operable breast cancer in Asia

Relations of Human Epidermal Growth Factor Receptor 2 (HER2) Expression and E-Cadherin (CDH1) Expression in Breast Cancer Patients

The aim of this study is to analyze the relations of Human Epidermal Growth Factor Receptor 2 (HER2) expression and E-Cadherin (CDH1) expression in breast cancer patients. To date, the synergistic effect of this CDH1/HER2 complex is not well clarified. The design of this study was cross-sectional with a total sample of 56 formalin-fixed paraffin tissue blocks that had been examined for HER2. Furthermore, CDHI expression was examined using the Immunohistochemistry staining technique with the Labeled Streptavidin Biotin Complex (LSAB) method. Bivariate analysis was performed using the Spearman correlation test with abnormally distributed data (p>0.05). Of the 56 data on breast cancer patients, most of the patients (87.5%) were diagnosed at the age of ≥40 years. The majority of cancer staging was IIIB, which was 42.9% of the total 56 patients. The study results shows that 80.0% of HER2-positive patients were in the strong CDH1 group. From these data, there is evidence of correlation between HER2 expression and CDH1 expression in breast cancer patients, however this correlation was not significant (p>0.05).The aim of this study is to analyze the relations of Human Epidermal Growth Factor Receptor 2 (HER2) expression and E-Cadherin (CDH1) expression in breast cancer patients. To date, the synergistic effect of this CDH1/HER2 complex is not well clarified. The design of this study was cross-sectional with a total sample of 56 formalin-fixed paraffin tissue blocks that had been examined for HER2. Furthermore, CDHI expression was examined using the Immunohistochemistry staining technique with the Labeled Streptavidin Biotin Complex (LSAB) method. Bivariate analysis was performed using the Spearman correlation test with abnormally distributed data (p>0.05). Of the 56 data on breast cancer patients, most of the patients (87.5%) were diagnosed at the age of ≥40 years. The majority of cancer staging was IIIB, which was 42.9% of the total 56 patients. The study results shows that 80.0% of HER2-positive patients were in the strong CDH1 group. From these data, there is evidence of correlation between HER2 expression and CDH1 expression in breast cancer patients, however this correlation was not significant (p>0.05)