THE ROLE OF CHEMOTHERAPHY OF BREAST CANCER

THE ROLE OF CHEMOTHERAPHY OF BREAST CANCE

BRCA1 and BRCA2: Lack of Certainty and Its Clinical Implications

AbstractIn this time of amounting cancer incidence and mortality, genetic testing may be greatly valuable in deciding on appropriate clinical management. It is unfortunate that the test is not a practical interrogative problem. When positive, the patients can settle down with what to do next, whereas when negative, their family members may breathe out in relief from unnecessary intensive surveillance and prophylaxis, and then there is VUS (Variants of Uncertain Significance).            How should a health provider deliver the elaboration and implication of VUS to a patient who had expended a lump sum of and had expected a level of certainty? Variants of UncertainSignificance have nowadays become a challenging spoiler in the setting of clinical management of cancer. How would one inform someone else on anything uninformative?            BRCA1 and BRCA2 are two genes with high penetrance in breast cancer. Since their functions as tumor suppressor genes and DNA repair regulators, their mutation effects are only visible when there is Loss of Heterozygosity. Mutation of BRCA1/2 gene can be demonstrated within the tissue specimen and blood sample DNA; that would mean it has occupied all tissues and is inheritable.            In the case of BRCA1 and BRCA2 mutations, 10-20% of all genetic test results will read VUS,  In one previous study of sixteen Indonesian patients, 13 (81,25%) patients had VUS. There were variants that had not been found in other population. Trans-academically speaking, the reclassification of VUS in BRCA1/2 gene is not merely a challenge to clarify its clinical impacts, but also an obligation to accomplish our community contribution to science.There can be a set of factors to suggest that a VUS may be a deleterious mutation:Co-segregation: when the variant comes with multiple and multigenerational incidence of cancer, it is possible.Epidemiology: when a case control study demonstrates prevalence discrepancy, it is possible.Co-occurrence with deleterious mutation: when the variant is shared within the same gene in other individuals, it is possible.Evolutionary data: when the sequence is carried across species, it is possible.Amino acid substitution: when the substitute is structurally similar, it is impossible.Loss of heterozygosity: when there is loss of a wild type allele in tumor specimen, it is possible.Functional analysis: should an in vitro assay demonstrate a loss of protein function, it is probable.The ultimate solution is not yet available. However, there is clinical significance for families with VUSs, only if that can confidently be classified as the presence or absence of the associated disease. That condition may be achieved by increasing the availability of genetic testing so that there can be a larger, open-access repertoire of VUSs

PELATIHAN PEMASARAN SYARIAH DALAM MERAIH KEBERKAHAN PADA USAHA SANTRIWAN SANTRIWATI DI YAYASAN ALKAMILAH SAWANGAN DEPOK

Pengabdian masyarakat ini berjudul Pelatihan Pemasaran Syariah Dalam Meraih Keberkahan Pada Usaha Santriwan Santriwati Di Yayasan AlKamilah Sawangan Depok. Tujuan pengabdian ini adalah memberikan pelatihan pemasaran syariah bagi masyarakat khususnya santriwan santriwati di yayasan AlKamilah Sawangan Depok guna meraih keberkahan. Metode pelaksanaan pengabdian ini adalah dengan Pelatihan yang dirancang untuk mengembangkan sumber daya manusia melalui rangkaian kegiatan identifikasi, pengkajian serta proses belajar yang terencana dengan 3 tahapan yaitu 1) Pengumpulan data dengan memberikan data wawancara kepada Santriwan santriwati keluhan dan kelemahan dalam memasarkan usaha secara syariah) 2). Pelatihan Pemasaran syariah dengan memberikan penyuluhan kepada Santriwan santriwati di yayasan Alkamilah. 3) Memberikan pendampingan Pelatihan pemasaran syariah dengan memberikan pelatihan kepada Santriwan santriwati di yayasan Alkamilah. Untuk mendukung hal itu diperlukan sebuah rencana kegiatan diantaranya adalah tahap persiapan yaitu dengan menyiapkan semua peralatan yang dibutuhkan untuk melaksanan kegiatan pkm, studi literatur dan melakukan koordinasi dengan instansi lembaga yayasan terkait serta ketua yayasan khususnya. Tahap enentuan Lokasi, yaitu dengan melakukan kunjungan ke lokasi untuk menentukan tempat pendampingan dan pelatihan pemasaran syariah. Tahap Perancangan implemnetasi dan pengawasan melalui pelatihan pemasaran syariah yang dilakukan oleh 5 orang dosen pada usaha dagang santriwan santriwati di yayasan Alkamilah sawangan depok. Kesimpulan dari pengabdian ini adalah peserta pengabdian sangat antusias terhadap pelatihan, hal ini ditunjukan dengan banyaknya antusiasme pertanyaan tentang proses pemasaran syariah dalam rangka mendukung aktifitas kegiatan usaha yang telah berjalan di yayasan Alkamilah baik melalui system kerjasama maupun system usaha mandiri. Kata Kunci: Pemasaran Syariah, Berkah, Bauran Pemasara

The Experience of Breast Reconstructive Microsurgery

Autologous techniques in oncoplastic breast surgery may result in graft donor site morbidity. Microsurgery has become a new surgical modality for breast reconstruction; it is a less invasive procedure. In recent experience, we have applied microsurgical technique in oncoplastic breast procedures to minimize morbidity.We reviewed the charts of breast cancer/tumor patients with microsurgical reconstruction.From February 2013 to July 2016, we performed 36 perforator flaps for breast reconstruction. The mean age of the patients was 44.4±6.7 years old, with the median tumor size of 3.7 (1.5-20) cm. No special type of carcinoma (NST) was accounted in 25 (69.4%) cases. Oncoplastic breast conserving surgery (OPS) was the procedure of choice in 17 (47.2%) cases and mastectomy was followed by free flap in 19 (52.8%) patients. In OPS, we used various perforator flaps to cover the defect. Thoracodorsal artery perforator flap (TDAP) was the most common technique used in 8 (22.2%) cases, then lateral intercostal artery (LICAP) flap in 6 (16.7%) cases, anterior intercostal artery (AICAP) flap in 1 (2.8%) cases, and superficial epigastric artery (SEAP) flap in 2 (5.6%) cases. Deep inferior artery perforator (DIEP) free flap was the reconstruction option after mastectomy. During follow-up with the mean time of 12.7±11.4 months, there were 1 local recurrence, 2 regional and systemic metastases, and 1 death due to cerebrovascular disease. There were no flap loss after pedicle perforator reconstruction but total flap necrosis occurred in 5 patients with DIEP free flap. In one patient, we successfully salvaged the flap that had venous congestion. There was no seroma at donor site and no limitation in abdominal wall function after DIEP reconstruction.In our experience, microsurgical reconstruction in breast surgery has been a safe procedure and has less donor site morbidity. Flap failure rate may be improved by refining microsurgical techniqu

Kadar C-erbb2 dalam Serum dan Saliva Pasien Kanker Payudara

C-erbB2 used as a marker for determining treatment and prognosis of breast cancer. The most often method used to evaluate c-erbB2 in tissue samples is by immunohistochemistry (IHC). Another method to evaluate c-erbB2 is measure the level of ECD (extra cellular domain) c-erbB2 were detached from the cell surface in serum and saliva. Saliva is used as a diagnostic tool because it can be collected noninvasive, easy. This study aimed to evaluate the levels of c-erbB2 in serum and saliva breast cancer patients compared to controls and to assess the possibility of the use of saliva as an alternative sample examination biomarker. The study using cross sectional design, implemented at Dharmais hospital of April-December 2012. The sample consisted of 55 subject of cancer patients and 56 controls. Specimens were taken from both groups, levels of c-erbB2 serum and saliva were measured by ELISA (cut off value ¥30 ng/ml) and the results compared to c-erbB2 IHC. Serum and salivary level of c-erbB2 increased at 10,9% and 7,3% of breast cancer patients. The levels of c-erbB2 in serum and saliva patients was higher than controls. Salivary levels of c-erbB2 correlated with serum (r=0.31). Sensitivity of serum c-erbB2 38% and 13% for saliva, spesivicity of 91% for both. PPV 50% and NPV 86% at serum, PPV 25% and NPV 82% at saliva. C-erbB2 can be detected in the serum and saliva and its overexpressed in 7-11% of breast cancer patients. Saliva may have potensial use as an alternative sample examination biomarkers in breast cancer.Keywords : C-Erbb2 ; Serum; Saliva; Breast CancerAbstrakPemeriksaan c-erbB2 berguna dalam menentukan terapi dan prognosis pasien kanker payudara. Carapaling sering untuk mengevaluasi ekspresi protein c-erbB2 dalam sampel jaringan adalah imunohistokimia (IHK). Cara lainnya adalah dengan menilai kadar ECD (extra cellular domain) c-erbB2 dalam serum dan saliva yang terlepas dari permukaan sel. Saliva digunakan sebagai spesimen diagnosis karena dapat dikumpulkan secara non-invasif, mudah, tanpa peralatan khusus untuk mengumpulkannya. Penelitian ini bertujuan untuk mengevaluasi kadar c-erbB2 dalam serum dan saliva pada pasien kanker payudara dibandingkan dengan kontrol serta menilai kemungkinan penggunaan saliva sebagai spesimen alternatif pemeriksaan penanda pada kanker payudara. Penelitian menggunakandesain cross sectional analitik, dilaksanakan di RS kanker Dharmais dari April-Desember 2012. Sampel terdiri dari: 55 subjek kelompok pasien kanker dan 56 kelompok kontrol. Spesimen diambil dari serum dan saliva kedua kelompok, kadar c-erbB2 diukur dengan metode ELISA dengan cut off value ¥30 ng/ml, kemudian hasil kadar c-erbB2 dibandingkan dengan c-erbB2 jaringan (IHK). Amplifikasi c-erbB2 jaringan terjadi pada 14,5% pasien kanker payudara sedangkan kadar c-erbB2 serum dan saliva meningkat pada 10,9% dan 7,3% pasien. Kadar rata-rata c-erbB2 serum dan saliva pada kelompok pasien kanker payudara lebih tinggi daripada kelompok kontrol. Kadar c-erbB2 dalam saliva berkorelasi dengan kadar c-erbB2 serum (r=0,31). Sensitifitas c-erbB2 pada serum 38%, 13% pada saliva. Spesifisitas serum dan saliva masing-masing 91% dengan PPV 50%, NPV 86% pada serum dan PPV 25%, NPV 82% pada saliva. C-erbB2 dapat terdeteksi di dalam serum dan saliva, mengalami overekspresi pada 7-11% pasien kanker payudara. Saliva merupakan sampel yang potensial digunakan sebagai sampel pemeriksaan biomarker kanker payudara.Kata kunci : C-Erbb2; Saliva; Serum; Kanker Payudar

Kelainan genetik pada kanker - sindrom kanker herediter

Selama dua dekade terakhir, pemahaman terhadap kanker yang bersifat herediter mengalamikemajuan yang cukup pesat. Dari seluruh jenis kanker, hanya sekitar 5-1O% yang diturunkan,dan sebagian besar mempunyai pola pewarisan autosomal dominan. Kelainan genetik yangdapat meningkatkan risiko terjadinya kanker disebut sebagai sindrom kanker herediter (SKH).Pada sebagian besar kasus, sindrom ini disebabkan oleh mutasi pada tumorsuppresso r gene,yaitu gen yang berperan dalam menghambat suatu sel untuk berkembang menjadi kanker.Selain itu, gen-gen lain yang berpotensi mengalami mutasi dalam kasus SKH adalah DNArepairgene, oncogen, dan berbagai gen yang terlibat dalam angiogenesis. Berbagai penemuanbidang genetik molekuler memberikan manfaat yang sangat signifikan dalam manajemenpasien dengan SKH. Sebagai contohnya adalah identifikasi berbagai gen yang memungkinkita untuk mendiagnosis SKH melalui analisa genetik. Dalam praktik klinik, tes genetik untuktujuan diagnosis cukup sering digunakan pada kanker kolon, payudara, ovarium, dan kelenjarendokrin. Berbagaikasus SKH yang paling sering dijumpaiantara lain hereditary nonpolyposiscolorectalcancer(HNPCC) atau Lynch syndrome,familialadenomatous polyposis, hereditarybreast and ovarian cancer, Li-Fraumeni syndrome, Cowden syndrome, da-n lain-lain. Dalammakalah ini, kami akan menggunakan beberapa kasus SKH yang sering dijumpai tersebutsebagai model untuk memberikan ilustrasi mengenai identifikasi, implikasi, dan tatalaksananSKH

A Comprehensive Exploration of Java Man: Bio-Cultural Evolution from Homo erectus to Homo sapiens

ABSTRACTAn overlap of time period between Homo erectus and Homo sapiens has not been confirmed. In the history of man, there have been two missing links: one between man and ape, and one between progressive Homo erectus and archaic Homo sapiens.  Specimen dating on Java Man has been discrepant among research groups, and the use of molecular biology in ancient specimens has been a novelty. This study intends to use fossilised specimens, to harvest DNA to be sequenced for ribosomal DNA analysis for comparative phylogeny among ancient and modern man and other hominids. Dental calculus will be analysed to identify starch, carbohydrate, and protein to illustrate paleo dietary pattern. Soil samples will be examined for pollen and phytoliths to elaborate on ancient ecosystem. Blood samples will be procured from indigenous people along the riverflow region of Bengawan Solo to analyse modern human DNA. We hope that we may reconstruct the evolution pathway, construct the phylogenetic tree between ancient and modern hominids, and discover the uniqueness of Homo sapiens sapiens.Keywords: Java Man, Ribosomal DNA, Hominid Phylogenetic

High Resolution Melting (HRM) Analysis for Genetic Changes in BRCA1/2 gene

Conventional mutation analysis requires a separation step and include single-strand conformational polymorphism (SSCP) analysis, denaturing gradient gel electrophoresis, heteroduplex analysis, denaturing HPLC, and temperature gradient capillary electrophoresis These methods require separation of PCR products on a gel or other matrix, often take hours to perform, and increase the risk of contamination in future reactions because PCR products are exposed to the environment. High Resolution Melting (HRM) can simplify the mutation scanning  analysis in BRCA 1/2 gene. DNA from affected patients and family members were amplified with Real-Time PCR reaction and followed by Sanger Sequencing to reconfirm the mutation status if mutation obtained by HRM Method. HRM Method was able to show distinction in differential curves of mutated BRCA 2 gene c.4600T>C, with codon modification of CAT>TAT, when compared to wildtype. To determine point mutation in a sample, this method requires two groups of experimental standards and standard curves. The first standard produced by using samples without mutation (wildtype/negative control) and the second standard produced by using samples with mutation (positive control), that have been confirmed with Sanger Sequencing. The sequencing analysis of the affected patient and the family members showed that a mutation occurred (BRCA2 c.4600T>C) and was segregated in the family history. This mutation caused amino acid alteration in BRCA2 protein (p.H1458Y). HRM Method is an excellent tool to analyze genetic modification of BRCA1/2 genes, especially to investigate co-segregation of mutated genes among family members of affected patient. This method can provide more sensitive results to determine mutation in patient, before using Sanger Sequencing analysis.Keyword: BRCA, HRM, Gene Mutatio

SIMPLE AND RAPID METHOD FOR THE SIMULTANEOUS ANALYSIS OF TAMOXIFEN, ENDOXIFEN, AND 4-HYDROXYTAMOXIFEN IN DRIED BLOOD SPOT USING LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY

Objective: Tamoxifen (TAM) is a hormonal therapy that is clinically proven to reduce breast cancer recurrence by blocking estrogen receptor, mainly through its active metabolites, 4-hydroxytamoxifen (4HT) and endoxifen (END), which have a higher affinity to ER than TAM itself. The objective of the present study was to develop and validate simple and rapid LC-MS/MS method for analysis TAM and its metabolites simultaneously in dried blood spot (DBS) sample for monitoring studies purposes. Methods: Optimization was done by evaluating several parameters that affect the efficiency of DBS preparation, such as blood spot volume, drying time and extraction method from the DBS paper. The effectiveness of chromatographic conditions was also optimized by varying flow rate, mobile phase combination and gradient. Clomiphene was used as the internal standard. Results: The result showed that preparation of 20 µl blood spot volume with 120 min of drying time and 25 min of extraction time using 1 ml methanol was the most efficient condition and also fulfilled recovery and matrix effect requirement according to FDA and EMA guidelines. The separation was performed on UPLC Class BEH C18 using formic acid 0.1%-formic acid 0.1% in acetonitrile (35:65) as the mobile phase in isocratic mode at 0.25 ml/min with a total analysis time of 4 min. Conclusion: This method has successfully fulfilled all validation requirements referring to EMA and FDA guidelines

One Step Nucleic Acid Amplification (OSNA) Study in Indonesia

ABSTRACTSentinel lymph node (SLN) is defined as the first of a few selected lymphatic nodes, into which lymphatic fluid from a primary tumor drains. Streamlined processing of sentinel lymph nodes (SLN) for detection of lymph node metastasis involves the able command over methodical blocks of SLN identification, surgical removal of SLN and SLN analysis. One Step Nucleic Acid Amplification (OSNA) method, which relies on CK19 mRNA expression to detect intraoperatively  lymph node metastases in breast cancer cases, emerged as a plausible alternative to the current gold standard that uses histopathological node analysis. Sixty selected axillary sentinel lymph nodes from thirty breast cancer patients. Sentinel lymph nodes were directly bi-halved after collection using customized lymph node cutting device (Sysmex), or scalpel. The first halves were subjected to histopathological examination and were stored in specimen containers containing fresh formaldehyde prior to processing. The adjacent halves were weighed to comply with the required mass by OSNA detection in the range of 50 – 600 mg and wrapped in clean foils for storage in -80°C prior to OSNA analysis. 60 SLNs were same diagnosis using both methods. 25 SLNs were negative and 25 SLNs were positive using both methods. 3 SLNs were positive on OSNA but negative on histology. Other 7 SLNs were negative on OSNA but positive on histology, and these 1 nodes contained only micrometastasis lesion. These results suggest that OSNA is a useful for detecting SLNs metastasis, but a copy number of CK19 might be an indepedent factor from prediction and prognosis of breast cancer.