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"Latar Belakang: Kanker payudara merupakan kanker dengan insidensi tertinggi kedua di dunia pada tahun 2018. Setiap 100.000 wanita di Indonesia, 40 mengidap kanker payudara. Mortalitas pada kanker payudara paling banyak disebabkan oleh kejadian metastasis organ viseral yang dilaporkan memiliki prognosis lebih buruk dibandingkan metastasis non viseral. Ekspresi reseptor hormonal (HR) dan proteinHER2 atau subtipe intrinsik molekular diindikasikan dapat memprediksi jenis atau lokasi metastasis kanker payudara. Karena itu, perlu ada penelitian tentang hubungan HR dan HER2 terhadap jenis metastasis kanker payudara, terutama pada populasi di Indonesia untuk memperkirakan perjalanan penyakit.Tujuan: Mengetahui hubungan antara reseptor hormonal dan HER2 terhadap jenis metastasis kanker payudara, viseral maupun non viseral.Metode: Penelitian dengan desain cross sectional ini menggunakan data dari sembilan puluh satu pasien kanker payudara dengan metastasis yang dipilih dengan cara consecutive sampling dari RSCM dan RS MRCCC Siloam. Status HR dan HER2 diambil dari pemeriksaan imunohistokimia, sedangkan jenis metastasis diambil dari hasil pemeriksaan radiologi atau patologi anatomi. Data diolah denganuji chi square dan disajikan dalam bentuk tabel.Hasil: Analisis bivariat antara HR dengan metastasis viseral menghasilkan nilai OR 0,549 (95% CI 0,165-1,829), dengan metastasis non viseral OR 1,533 (95% CI 0,565-4,157), dan dengan kedua metastasis viseral dan non viseral OR 0,960 (95% CI 0,351-2,624). Untuk analisis antara protein HER2 dengan metastasis viseralmenghasilkan OR 2,333 (95% CI 0,825-6,599), dengan metastasis non viseral OR 0,538 (95% CI 0,223-1,302), dan dengan kedua metastasis viseral dan non viseral OR 1,061 (95% CI 0,442-2,549). Semua analisis menghasilkan p>0,05.Kesimpulan: Tidak ditemukan adanya hubungan yang bermakna antara HR maupun HER2 terhadap jenis metastasis kanker payudaraBackground: Breast cancer is a cancer with the second highest incidence in the world in 2018. For every 100,000 women in Indonesia, 40 suffer from breast cancer. Mortality in breast cancer is mostly caused by the incidence of visceral organ metastases which are reported to have a worse prognosis than non-visceral metastases. Hormonal receptor (HR) and protein expressionHER2 or molecular intrinsic subtypes are indicated to predict the type or location of breast cancer metastases. Therefore, there needs to be research on the relationship between HR and HER2 to the type of breast cancer metastases, especially in the population in Indonesia to estimate the course of the disease.Objective: To determine the relationship between hormonal receptors and HER2 on the type of breast cancer metastasis, visceral and non-visceral.Methods: This cross-sectional design study used data from ninety-one breast cancer patients with metastases selected by consecutive sampling from RSCM and MRCCC Siloam Hospital. HR and HER2 status were taken from immunohistochemical examination, while the type of metastasis was taken from the results of radiological examination or anatomical pathology. Data processed with chi square test and presented in tabular form.Results: Bivariate analysis of HR with visceral metastases resulted in OR 0.549 (95% CI 0.165-1.829), with non-visceral metastases OR 1.533 (95% CI 0.565-4.157), and with both visceral and non-visceral metastases OR 0.960 (95% CI 0.351-2.624). For analysis between HER2 protein and visceral metastases resulted in an OR of 2.333 (95% CI 0.825-6.599), with non-visceral metastases OR 0.538 (95% CI 0.223-1.302), and with both visceral and non-visceral metastases OR 1.061 (95% CI 0.442-2.549). All analyzes yielded p>0.05.Conclusion: There was no significant relationship between HR and HER2 on the type of breast cancer metastases"

"Latar belakang dan tujuan: Kanker payudara adalah kanker yang sering didiagnosis dan menjadi penyebab kematian akibat kanker yang paling tinggi pada perempuan di dunia. Berdasarkan data registrasi di Rumah Sakit Kanker Dharmais pada tahun 2003-2007, kanker payudara menjadi keganasan terbanyak yaitu sebesar 40,58% dari seluruh kanker. Berbagai tatalaksana dilakukan sesuai dengan protokol pengobatan yang berlaku di RS Kanker Dharmais. Meskipun telah banyak kemajuan dalam penanganan kanker payudara, tetapi masih sering dijumpai rekurensi baik rekurensi lokal, regional maupun perluasan ke organ lain. Adanya rekurensi sering dihubungkan dengan meningkatnya resiko kematian, dimana dikatakan pada kanker payudara resiko kematian 5% lebih tinggi. Penelitian ini bertujuan untuk melihat hubungan hasil pemeriksaan Estrogen - Progresteron Reseptor (ER-PR), Human Epidermal Growth Factor Reseptor-2 (Her2), dan Indeks Proliferasi (KI-67) terhadap rekurensi kanker payudara berdasarkan hasil pencitraan 18F-FDG PET/CT, pada pasien - pasien kanker payudara yang telah dilakukan terapi sesuai prosedur. Metode: Penelitian ini merupakan proses analisis dengan desain retrospektif cohort study pada pasien yang didiagnosis kanker payudara yang telah di terapi sesuai prosedur dan sembuh, serta telah dilakukan pemeriksaan 18F-FDG PET/CT. Hasil: Uji Mutlak Fisher KI-67 didapatkan hasil nilai yang signifikan yang berarti tidak hubungan bermakna antara hasil imunohistokimia KI-67 tinggi dengan rekurensi kanker payudara. Kesimpulan: Hasil penelitian ini tidak menunjukkan hubungan yang bermakna antara kanker payudara subtipe Luminal B dan Triple Negative dengan rekurensi kanker payudara dan Tidak terdapat hubungan yang bermakna antara hasil ER positif, PR positif ataupun Her2 positif terhadap rekurensi kanker payudara.

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Background and purpose: Breast cancer is frequently diagnosed cancer and cause of cancer deaths in women are highest in the world. Based on registration data in Dharmais Cancer Hospital in the years 2003-2007, breast cancer is a malignancy that is equal to 40.58% majority of all cancers. Various management of treatment carried out in accordance with the applicable protocol Dharmais Cancer Hospital. Although progress has been made in the treatment of breast cancer, but recurrence is common both local recurrence, regional and extension to other organs. Recurrence is often associated with increased risk of death, which is said in the breast cancer death risk 5% higher. This study aimed to examine the relationship examination Estrogen - progesterone receptors (ER-PR), Human Epidermal Growth Factor Receptor-2 (Her2), and proliferation index (Ki-67) against the recurrence of breast cancer based on imaging of 18F-FDG PET / CT , in patients - patients who have breast cancer therapy according to the procedure.

Methods: This study is the retrospective analysis of a cohort study design in patients diagnosed with breast cancer who had been in therapy according to the procedure and recovery, and has been examined 18F-FDG PET / CT.

Results: Absolute Fisher Test KI-67 showed significant value, which means there is significant relationship between the results of immunohistochemical high KI-67 with a recurrence of cancer.

Conclusion: The results of this study showed no significant association between breast cancer subtypes Luminal B and Triple Negative breast cancer with recurrence and There is a significant association between the results of ER positive, PR positive and Her2 positive breast cancer on recurrence."

"ABSTRAKLatar Belakang: Indeks massa tubuh dapat meningkatkan risiko kanker payudara. Pada penelitian sebelumnya didapatkan bahwa indeks massa tubuh yang memasuki kategori obesitas dapat memperburuk prognosis penyakit kanker payudara. Selain indeks massa tubuh, status reseptor hormonal juga menjadi hal yang penting untuk menentukan terapi kanker payudara. Namun, belum diketahui apakah terdapat hubungan antara perubahan indeks massa tubuh sebelum dan sesudah terapi dan status reseptor hormonal terhadap respon terapi kanker payudara yang dinilai dengan ada atau tidaknya residu. Tujuan: Mengetahui pengaruh perubahan indeks massa tubuh dan status reseptor hormonal terhadap respon terapi kanker payudara yang dinilai dengan residu pasca terapi.Metode: Sebanyak 111 data dari rekam medis pasien diambil dengan metode consecutive sampling berdasarkan kriteria inklusi dan eksklusi. Data indeks massa tubuh didapatkan melalui berat badan dan tinggi badan yang diukur sebelum dan sesudah terapi. Pengukuran dilakukan selama rangkaian pemberian kemoterapi. Jika tinggi badan yang didapatkan pada pengukuran sebelum dan sesudah terapi berbeda, maka akan diambil rata-rata. Sedangkan data status reseptor hormonal didapatkan dengan melihat laporan pemeriksaan immunohistokimia. Untuk melihat respon pasien terhadap terapi digunakan laporan hasil pemeriksaan pencitraan.Hasil: Berdasarkan analisis bivariat yang dilakukan, didapatkan hubungan antara perubahan indeks massa tubuh terhadap residu kanker payudara pasca terapi (p 0,018; p<0,05). Dan tidak didapatkan hubungan antara status reseptor hormonal dengan residu kanker payudara pasca terapi (p 0,803; p>0,05) serta hubungan antara status reseptor hormonal dan perubahan indeks massa tubuh secara bersamaan (p 0,087; p>0,05).Kesimpulan: Peningkatan indeks massa tubuh dapat meningkatkan risiko residu kanker payudara pasca terapi. Sedangkan, status reseptor hormonal tidak memiliki hubungan dengan residu kanker payudara pasca terapi. "

"Latar Belakang: Obesitas menjadi faktor risiko independen dan faktor prognostik pada kanker payudara primer. Jaringan lemak berlebih akan meningkatkan kadar estrogen dalam darah, sehingga memicu proliferasi sel kanker, terutama sel dengan reseptor estrogen dan progesteron yang positif. Belum ada studi mengenai hubungan antara obesitas dengan karakteristik reseptor hormon kanker payudara primer di Indonesia. Metode: Kami mengumpulkan kasus kanker payudara primer yang terdiagnosis dan menjalani pemeriksaan imunohistokimia di RSUPN Cipto Mangunkusumo tahun 2017. Subyek kemudian dikelompokkan menjadi kelompok obesitas dan nonobesitas. Karakteristik ER dan PR kedua kelompok dibandingkan. Hasil dan Diskusi: Kami memperoleh 202 kasus kanker payudara primer, dengan 89 kasus (44%) obesitas dan 113 kasus (56%) non-obesitas. Rerata IMT dari subyek adalah 24,45 (SD±4,3). Kedua kelompok seragam dari segi usia, status menopause, stadium, gambaran histopatologis, dan derajat keganasan. Tidak didapatkan hubungan yang bermakna antara obesitas dengan ER maupun PR. Dilakukan analisis korelasi antara IMT dengan persentase ekspresi reseptor hormon, namun tidak ditemukan hubungan yang bermakna. Hasil ini berbeda dengan studi lainnya. Perbedaan hasil dapat disebabkan oleh perbedaan karakteristik subyek dan faktor lain yang dapat mempengaruhi ekspresi reseptor hormon. Kesimpulan: Tidak didapatkan hubungan antara obesitas dan karakteristik reseptor hormon kanker payudara primer RSUPN Cipto Mangunkusumo tahun 2017.Backgrounds: Obesity is an independent risk factor and prognostic factor of primary breast cancer. Abundant adipose tissue would lead to increment of blood estrogen level, thus promoting proliferation of cancer cell, especially those with positive estrogen receptor (ER) and progesterone receptor (PR). No previous study explained the association between obesity and hormone receptor characteristics of primary breast cancer in Indonesia. Methods: We collected cases of primary breast cancer which are diagnosed and undergone immunohistochemistry examination at Cipto Mangunkusumo General Hospital in 2017. The subjects were divided into obese group and non-obese group. The ER and PR characteristics of both groups were compared. Result and Discussion: We collected 202 cases of primary breast cancer, with 89 cases (44%) in obese group and 113 cases (56%) in non-obese group. The mean body mass index (BMI) of the subjects was 24,45 (SD±4,3). Both groups were similar in terms of age, menopausal status, stage, histopathological morphology and grade. No significant association was found between obesity and ER or PR. We analysed correlation between BMI and the percentage of expressed hormone receptor, but no correlation was found. This finding did not conform with other Western studies. Difference in characteristics of the subjects and other hormonal factors might contribute to the outcome. Conclusion: There was no association between obesity and hormone receptor characteristics of primary breast cancer at Cipto Mangunkusumo General Hospital in 2017."

"[ABSTRAKTujuan: Menentukan hubungan ukuran tumor dan derajat histopatologi dengan metastasis tulang pada pasien kanker payudara berusia dibawah 40 tahun di RS Kanker Dharmais, membantu meningkatkan kualitas tatalaksana bagi klinisi.Metode: Analisa menggunakan data sekunder. Hasil ukuran tumor dikelompokkan menjadi ≤ 5 cm dan > 5 cm berdasarkan AJCC TNM staging system diperoleh melalui pencitraan radiologi payudara dari sistem PACS dan derajat histopatologi menurut derajat histopatologi Nottingham kombinasi diperoleh dari hasil ekspertise patologi anatomi, serta evaluasi metastasis tulang menggunakan skintigrafi tulang berdasarkan total populasi pasien kanker payudara berusia dibawah 40 tahun.Hasil: Jumlah subyek penelitian 32 perempuan kanker payudara berusia dibawah 40 tahun periode Januari 2011 hingga Juli 2014 di RS Kanker Dharmais. Tidak ada hubungan yang bermakna antara ukuran tumor dengan metastasis tulang (P= 0,715 (Fisher exact test), OR=1,71 (0,32-9,36)). Terdapat hubungan yang bermakna antara derajat histopatologi dengan metastasis tulang (P=0,010, P < 0,05).Dari 10 subyek derajat histopatologi tinggi, ternyata semua subyek mengalami metastasis tulang negatif. Pada subyek dengan derajat histopatologi sedang didapatkan 8 dari 15 subyek yang mengalami metastasis tulang. Pada subyek penelitian dengan derajat histopatologi rendah didapatkan 6 dari 7 subyek mengalami metastasis tulang negatif. Rerata usia 33,2 tahun dan simpang baku 3,7 tahun memiliki kejadian metastasis tulang lebih tinggi (P=0,024). Terdapat data tambahan dan ditemukan hubungan yang bermakna antara Cerb-b2/HER-2 positif dengan metastasis tulang (P=0,049 (P < 0,05), Odds Ratio=5,67 (0,84 ? 43,16)).Prevalensi metastasis tulang yaitu sebesar 28,1%.Kesimpulan: Pasien kanker payudara berusia dibawah 40 tahun dengan ukuran tumor besar tidak memiliki kejadian metastasis tulang lebih tinggi. Pasien dengan derajat histopatologi tinggi tidak memiliki kejadian metastasis tulang lebih tinggi, namun ditemukan angka kejadian metastasis tulang lebih tinggi pada derajat histopatologi sedang. Terdapat dua faktor lain yang juga mempunyai hubungan dengan kejadian metastasis tulang yaitu usia dan Cerb-br/HER-2. Rerata usia 33,2 tahun dengan simpang baku 3,7 tahun pada pasien kanker payudara berusia di bawah 40 tahun memiliki kejadian metastasis tulang lebih tinggi. Cerb-b2/HER-2 positif pada pasien kanker payudara berusia di bawah 40 tahun memiliki kejadian metastasis tulang lebih tinggi dengan resiko kejadian sebesar 5,67 kali. Prevalensi metastasis tulang cukup tinggi pada pasien kanker payudara berusia dibawah 40 tahun yaitu sebesar 28,1%.

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ABSTRACTObjective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%.;Objective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%.;Objective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%., Objective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%.]"

"Latar Belakang: Sel punca kanker merupakan populasi sel minor yang memiliki kemampuan self-renewal dan proliferasi tak terbatas sehingga bersifat tumorigenik dan diduga berperan dalam penurunan sensitivitas terhadap berbagai terapi kanker. Tamoksifen merupakan terapi lini pertama pada kanker payudara ER positif namun penggunaan jangka panjangnya menimbulkan masalah resistensi. Beberapa faktor yang diduga berperan dalam penurunan sensitivitas sel terhadap Tamoksifen yakni modulasi pensinyalan estrogen melalui ER?66; dan ER?36 (yang diketahui memperantarai pensinyalan non-genomik), serta ekspresi transporter effluks seperti MRP2 yang berperan dalam penurunan kadar Tamoksifen intraseluler. Penelitian ini bertujuan untuk menganalisis efek pemaparan Tamoksifen berulang pada sel punca kanker payudara CD24-/CD44+, dalam kaitannya mengenai sensitivitas terapi melalui perubahan ekspresi estrogen reseptor alfa dan transporter efluks MRP2.Metode: Selpunca kanker payudara CD24-/CD44+ dipaparkan Tamoksifen 1 ?M selama 21 hari dengan DMSO sebagai kontrol negatif. Viabilitas sel setelah pemaparan Tamoksifen diuji dengan metode trypan blue exclusion. Sifat tumorigenik sel setelah pemaparan (CD24-/CD44+(T)) diuji dengan mammossphere formation assay dan dibandingkan dengan sel CD24-/CD44+(0) yang belum dipaparkan Tamoksifen. Ekspresi mRNA Oct4, c-Myc, ER?66, ER?36 dan MRP2 dianalisis dengan one step quantitative RT-PCR.Hasil: Terjadi penurunan sensitivitas sel punca kanker payudara CD24-/CD44+(T) yang dipaparkan Tamoksifen selama 21 hari yang ditunjukkan dengan kenaikan viabilitas sel hingga 125,2%. Tamoksifen tidak dapat menekan sifat tumorigenik sel CD24-/CD44+(T) yang dibuktikan melalui jumlah mammosfer yang tidak berbeda bermakna dibandingkan dengan CD24-/CD44+(0). Penurunan sensitivitas sel CD24-/CD44+(T) juga dibuktikan melalui peningkatan ekspresi Oct4 dan c-Myc; keduanya merupakan petanda pluripotensi dan c-Myc juga dikenal sebagai petanda keganasan. Parameter penurunan sensitivitas seperti ER?66, ER?36 dan MRP2 juga menunjukkan peningkatan ekspresi pada hari ke-15 namun menurun kembali pada hari ke-21 yang menunjukkan adanya mekanisme regulasi lain yang mungkin terlibat dalam penurunan sensitivitas sel punca kanker payudara terhadap Tamoksifen.Kesimpulan: Pemaparan Tamoksifen berulang dapat menurunkan sensitivitas sel punca kanker payudara CD24-/CD44+ melalui perubahan ekspresi estrogen reseptor alfa dan transporter efluks MRP2.

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Background: Cancer stem cells are minor population of cells possessing self-renewal and unlimited proliferation abilities which support their tumorigenicity and role in decreased sensitivity to many cancer therapies. Tamoxifen is a first line therapy for breast cancer patients with positive ER status. Nonetheless, after 5 years of its long term use eventually leads to recurrence and resistance in 50% of patients receiving tamoxifen therapy. Among some factors that might play role in decreased sensitivity to tamoxifen are modulation of estrogen signaling through ER?66 and ER?36 (the latter known for its non-genomic estrogen signaling), and expression of efflux transporter such as MRP2 responsible for decreased intracellular tamoxifen level. The objective of this study is to analyze the effects of long term tamoxifen exposure toward decreased sensitivity of the breast cancer stem cells CD24-/CD44+ through changes in expression of estrogen receptor alpha and efflux transporter MRP2.

Methods: Breast cancer stem cells CD24-/CD44+ were exposed to 1 ?M tamoxifen for 21 days with DMSO as negative control. After exposure with 1 ?M tamoxifen, the cell viability were tested by the trypan blue exclusion method. Cell tumorigenicity of tamoxifen-exposed CD24-/CD44+(T) and CD24-/CD44+(0) (before treatment) were tested by the mammosphere formation assay. The expression of Oct4, c-Myc, ER?66, ER?36 andMRP2 mRNAs were analyzed by one step quantiative RT-PCR.

Results: A decreased sensitivity of the breast cancer stem cells CD24-/CD44+ exposed with 1 ?M tamoxifen for 21 days was observed as indicated by an increased cell viability up to 125.2%. In the presence of tamoxifen, breast cancer stem cells CD24-/CD44+(T) exhibited tumorigenic properties as indicated in no significant difference in the formation of mammosphere unit compared to those of CD24-/CD44+(0). After exposure with 1 ?M tamoxifen for 21 days, an elevated level of Oct4 and c-Myc expressions were observed; both are known as pluripotency markers and the latter also known as marker of aggresiveness. Parameters for a decreased sensitivity such as ER?66, ER?36 and MRP2 also exhibited an elevated expression after 15 days of exposure, but the decreased expression after 21 days of exposure suggests that there might be another mechanism involved in decreased sensitivity of the breast cancer stem cells toward tamoxifen.

Conclusion: Long term tamoxifen exposure may decrease the sensitivity of the breast cancer stem cells CD24-/CD44+ through changes in expression of estrogen receptor alpha and efflux transporter MRP2."

"Latar Belakang: Sel punca kanker merupakan populasi sel minor yang memiliki kemampuan self-renewal dan proliferasi tak terbatas sehingga bersifat tumorigenik dan diduga berperan dalam penurunan sensitivitas terhadap berbagai terapi kanker. Tamoksifen merupakan terapi lini pertama pada kanker payudara ER positif namun penggunaan jangka panjangnya menimbulkan masalah resistensi. Beberapa faktor yang diduga berperan dalam penurunan sensitivitas sel terhadap Tamoksifen yakni modulasi pensinyalan estrogen melalui ERα66; dan ERα36 (yang diketahui memperantarai pensinyalan non-genomik), serta ekspresi transporter effluks seperti MRP2 yang berperan dalam penurunan kadar Tamoksifen intraseluler. Penelitian ini bertujuan untuk menganalisis efek pemaparan Tamoksifen berulang pada sel punca kanker payudara CD24-/CD44+, dalam kaitannya mengenai sensitivitas terapi melalui perubahan ekspresi estrogen reseptor alfa dan transporter efluks MRP2.Metode: Selpunca kanker payudara CD24-/CD44+ dipaparkan Tamoksifen 1 μM selama 21 hari dengan DMSO sebagai kontrol negatif. Viabilitas sel setelah pemaparan Tamoksifen diuji dengan metode trypan blue exclusion. Sifat tumorigenik sel setelah pemaparan (CD24-/CD44+(T)) diuji dengan mammossphere formation assay dan dibandingkan dengan sel CD24-/CD44+(0) yang belum dipaparkan Tamoksifen. Ekspresi mRNA Oct4, c-Myc, ERα66, ERα36 dan MRP2 dianalisis dengan one step quantitative RT-PCR.Hasil: Terjadi penurunan sensitivitas sel punca kanker payudara CD24-/CD44+(T) yang dipaparkan Tamoksifen selama 21 hari yang ditunjukkan dengan kenaikan viabilitas sel hingga 125,2%. Tamoksifen tidak dapat menekan sifat tumorigenik sel CD24-/CD44+(T) yang dibuktikan melalui jumlah mammosfer yang tidak berbeda bermakna dibandingkan dengan CD24-/CD44+(0). Penurunan sensitivitas sel CD24-/CD44+(T) juga dibuktikan melalui peningkatan ekspresi Oct4 dan c-Myc; keduanya merupakan petanda pluripotensi dan c-Myc juga dikenal sebagai petanda keganasan. Parameter penurunan sensitivitas seperti ERα66, ERα36 dan MRP2 juga menunjukkan peningkatan ekspresi pada hari ke-15 namun menurun kembali pada hari ke-21 yang menunjukkan adanya mekanisme regulasi lain yang mungkin terlibat dalam penurunan sensitivitas sel punca kanker payudara terhadap Tamoksifen.Kesimpulan: Pemaparan Tamoksifen berulang dapat menurunkan sensitivitas sel punca kanker payudara CD24-/CD44+ melalui perubahan ekspresi estrogen reseptor alfa dan transporter efluks MRP2.

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Background: Cancer stem cells are minor population of cells possessing self-renewal and unlimited proliferation abilities which support their tumorigenicity and role in decreased sensitivity to many cancer therapies. Tamoxifen is a first line therapy for breast cancer patients with positive ER status. Nonetheless, after 5 years of its long term use eventually leads to recurrence and resistance in 50% of patients receiving tamoxifen therapy. Among some factors that might play role in decreased sensitivity to tamoxifen are modulation of estrogen signaling through ERα66 and ERα36 (the latter known for its non-genomic estrogen signaling), and expression of efflux transporter such as MRP2 responsible for decreased intracellular tamoxifen level. The objective of this study is to analyze the effects of repeated tamoxifen exposure toward decreased sensitivity of the breast cancer stem cells CD24-/CD44+ through changes in expression of estrogen receptor alpha and efflux transporter MRP2.

Methods: Breast cancer stem cells CD24-/CD44+ were exposed to 1 μM tamoxifen for 21 days with DMSO as negative control. After exposure with 1 μM tamoxifen, the cell viability were tested by the trypan blue exclusion method. Cell tumorigenicity of tamoxifen-exposed CD24-/CD44+(T) and CD24-/CD44+(0) (before treatment) were tested by the mammosphere formation assay. The expression of Oct4, c-Myc, ERα66, ERα36 andMRP2 mRNAs were analyzed by one step quantiative RT-PCR.

Results: A decreased sensitivity of the breast cancer stem cells CD24-/CD44+ exposed with 1 μM tamoxifen for 21 days was observed as indicated by an increased cell viability up to 125.2%. In the presence of tamoxifen, breast cancer stem cells CD24-/CD44+(T) exhibited tumorigenic properties as indicated in no significant difference in the formation of mammosphere unit compared to those of CD24-/CD44+(0). After exposure with 1 μM tamoxifen for 21 days, an elevated level of Oct4 and c-Myc expressions were observed; both are known as pluripotency markers and the latter also known as marker of aggresiveness. Parameters for a decreased sensitivity such as ERα66, ERα36 and MRP2 also exhibited an elevated expression after 15 days of exposure, but the decreased expression after 21 days of exposure suggests that there might be another mechanism involved in decreased sensitivity of the breast cancer stem cells toward tamoxifen.

Conclusion: Repeated tamoxifen exposure may decrease the sensitivity of the breast cancer stem cells CD24-/CD44+ through changes in expression of estrogen receptor alpha and efflux transporter MRP2."

"Kanker payudara merupakan kanker paling sering pada wanita dan merupakan penyebab kematian kedua tersering dari seluruh kanker di dunia. Metastasis merupakan penyebab utama kematian pasien kanker payudara. Status kelenjar getah bening (KGB) digunakan untuk mengidentifikasi prognosis, stadium tumor, serta penentuan modalitas terapi. Nottingham Prognostic Index (NPI) juga dapat digunakan dalam memprediksi prognosis dan kesintasan pasien. Salah satu biomarker yang diharapkan dapat memprediksi adanya metastasis KGB dan memperkirakan kesintasan pasien yaitu CD133. Penelitian ini bertujuan untuk mengetahui ekspresi protein CD133, sehingga dapat digunakan sebagai faktor penanda kemungkinan terjadinya metastasis KGB dan memprediksi kesintasan pasien pada karsinoma payudara invasif no special type (NST). Penelitian ini menggunakan desain kasus kontrol terhadap kasus mastektomi karsinoma payudara invasif NST di RSCM periode Januari 2019 sampai Desember 2022. Sampel penelitian dibagi menjadi 2 kelompok, yaitu 30 kasus karsinoma payudara invasif NST dengan metastasis KGB dan 30 kasus tanpa metastasis KGB. Pengambilan sampel penelitian dilakukan secara consecutive sampling. Dihitung skor NPI. Didapatkan perbedaan bermakna ekspresi CD133 pada karsinoma payudara invasif NST dengan dan tanpa metastasis KGB. Ekspresi CD133 tinggi lebih banyak ditemukan, yaitu 24 kasus (80%). Didapatkan korelasi yang bermakna antara ekspresi CD133 dan skor NPI. Ekspresi CD133 tinggi lebih banyak ditemukan pada kasus dengan NPI >5,4 (buruk), yaitu 20 kasus (66,7%).

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Breast cancer is the most prevalent malignancy in women and the second largest cause of cancer-related death worldwide. The main cause of breast cancer’s high death rate is metastasis. Lymph node status is used to identify prognosis, tumor stage, and determine therapeutic modalities. Nottingham Prognostic Index (NPI) can be used to predict prognosis and patient survival. The biomarker that can predict lymph node metastasis and predict patient survival is CD133. This study aims to determine the expression of CD133 protein, which can be used as a marker for the possibility of lymph node metastasis and predict patient survival in invasive breast carcinoma of no special type. This study used a case control design on a mastectomy operation for invasive breast carcinoma NST cases at RSCM from January 2019 to December 2022. The study sample was divided into 2 groups, 30 cases of invasive breast carcinoma NST with lymph node metastasis and 30 cases without lymph node metastasis. The sample was taken by consecutive sampling. NPI score was calculated. There was a significant difference in CD133 expression in invasive breast carcinoma NST with and without lymph node metastasis. High CD133 expression was found more in invasive breast carcinoma NST with lymph node metastasis (24 cases or 80%). There was significant correlation between CD133 expression and NPI score. High CD133 expression was found more in invasive breast carcinoma NST with poor NPI (20 cases or 66,7%). "

"Latar Belakang: HER2 merupakan protoonkogen menjadi dasar pemberian terapi sel target pada adenokarsinoma gaster stadium lanjut. Penelitian hubungan antara gambaran klinis, endoskopi dan histopatologi dengan ekspresi HER2 masih menunjukkan hasil yang berbeda. Penelitian tentang HER2 sebagai prediktor kesintasan juga menunjukkan hasil yang berbeda. Penelitian ini bertujuan untuk mengetahui hubungan gambaran klinis, endoskopi, histopatologi dengan ekspresi HER2 dan hubungan antara ekspresi HER2 dengan kesintasan dua tahun.Metode: Penelitian kohort retrospektif pada subyek adenokarsinoma gaster yang baru terdiagnosis, berusia ³ 18 tahun di 4 rumah sakit di Jakarta, berobat dari 2015-2019, memenuhi kriteria inklusi: memiliki rekam medis yang lengkap, hasil pemeriksaan gastroskopi, blok parafin hasil biopsi. Slide biopsi diwarnai dengan pewarnaan imunohistokimia HER2 dan diinterpretasi dengan kriteria ToGA. Analisis statistik deskriptif dan bivariat dengan menggunakan chi square/tes fisher untuk menilai hubungan antara gambaran klinis, endoskopi, dan histopatologi dengan ekspresi HER2. Analisis kesintasan, bivariat dan multivariat dengan Cox-regresi menentukan pengaruh ekspresi HER2 terhadap kesintasan dua tahun.Hasil: Ekspresi HER2 positif ditemukan pada 12,3% subyek (15 dari 122 subyek). Ekspresi HER2 cenderung lebih tinggi pada metastasis ke hati, klasifikasi Borrman tipe I/II, diferensiasi baik/sedang, tipe intestinal berdasarkan Klasifikasi Lauren memiliki dengan proporsi masing-masing: 17.6% RR(IK95%)=1.726 (0.665-4.480), 16.1% RR(IK95%)=1,768(0,670-4,662), 14.3% RR(IK95%)=1,304(0,505-3,363), 13.9% RR(IK95%)=1,389(0,505-3,817).Ekspresi HER2 positif tidak berhubungan dengan kesintasan dua tahun, HR (IK95%)=1,12(0,609-2,058).Simpulan: Matastasis hati, klasifikasi Borrman, letak tumor, diferensiasi tumor dan klasifikasi Lauren tidak berhubungan bermakna secara statistik terhadap ekspresi HER2. Ekspresi HER2 positif tidak berhubungan dengan kesintasan dua tahun pada adenokarsinoma gaster.

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Background: HER2 is a proto-oncogene which important for administering of target cell therapy in advanced gastric adenocarcinoma. Research on clinical, endoscopic, and histopathological features shown conflicting in association with HER2 expression. Studies on HER2 as a predictor of survival still show different results. This study aims to determine association of the clinical, endoscopic, and histopathological features with HER2 expression and association of HER2 expression with 2-year survival.

Methods: A retrospective cohort study on newly diagnosed gastric adenocarcinoma subjects, aged 18 years old at 4 hospitals in Jakarta, receiving treatment from 2015-2019, meeting the inclusion criteria: having complete medical record, results of gastroscopy examination, and paraffin block tumor biopsy results. The biopsy slides were stained with HER2 immunohistochemical staining and interpreted according to the ToGA criteria. Descriptive and bivariate analysis by using chi-square or fisher's test assessed the relationship between clinical, endoscopic, and histopathological features with HER2 expression. Survival, bivariate and multivariate analysis with cox regression method were used to determine the effect of HER2 expression on 2-year survival.

Results: Positive HER2 expression was found in 12.3% of subjects (15 of 122 subjects). HER2 expression tends to be higher in metastases to the liver, Borrman classification type I/II, good/moderate differentiation, intestinal type based on Lauren's classification has the respective proportions:17.6% RR (95%CI)=1.726 (0.665-4.480), 16.1% RR (95%CI)=1,768 (0,670-4,662), 14.3% RR (95%CI)=1,304 (0,505-3,363), 13.9% RR (95%CI)=1,389 (0,505-3,817). Positive HER2 expression was not associated with 2-year survival with HR (95%CI) =1.12 (0.609-2.058)."

"Latar Belakang: Penurunan sensitivitas hingga resistensi terhadap tamoksifen sering terjadi dalam pengobatan kanker payudara jangka panjang. Salah satu penyebab utamanya adalah peningkatan ekspresi transporter efluks P-glikoprotein (P-gp) dan Breast Cancer Resistance Protein (BCRP). Kurkumin diketahui sebagai penghambat P-gp dan BCRP. Pemberian kurkumin pada sel yang telah menurun sensitivitasnya terhadap tamoksifen diharapkan mampu meningkatkan sensitivitas sel kanker payudara terhadap tamoksifen melalui penghambatan kedua transporter tersebut. Metode: Sel MCF-7 dipaparkan tamoksifen 1 µM selama 10 pasasi (sel MCF-7(T)), kemudian dianalisis perubahan sensitivitas sel terhadap tamoksifen melalui viabilitas sel dan ekspresi mRNA P-gp dan BCRP. Pada sel MCF-7(T), kurkumin diberikan dalam dosis 5, 10, dan 20 µM dengan atau tanpa tamoksifen selama 5 hari dan dianalisis viabilitas sel dan ekspresi mRNA P-gp dan BCRP pada hari ke-2 dan 5. Sebagai kontrol positif, verapamil 50 µM digunakan sebagai penghambat P-gp, ritonavir 15 µM dan nelfinavir 15 µM sebagai penghambat BCRP. Hasil: Setelah diberikan tamoksifen 1 µM selama 10 pasasi (44 hari), sel MCF-7(T) menurun sensitivitasnya terhadap tamoksifen yang dibuktikan dengan terjadinya pergeseran CC50 sebesar 32,08 kali, peningkatan viabilitas sel sebesar 106,4%, dan peningkatan ekspresi mRNA P-gp dan BCRP sebesar 10,82 kali dan 4,04 kali. Pemberian kurkumin dengan atau tanpa tamoksifen selama 5 hari dapat menurunkan viabilitas sel dan ekspresi mRNA P-gp dan BCRP (p < 0,05). Kesimpulan: Kurkumin meningkatkan sensitivitas sel MCF-7(T) terhadap tamoksifen yang ditandai dengan penurunan viabilitas sel dan ekspresi mRNA P-gp dan BCRP. Peningkatan sensitivitas tersebut diduga terjadi melalui penghambatan ekspresi mRNA P-gp dan BCRP oleh kurkumin.

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Background: Decrease of sensitivity or resistance to tamoxifen occurs after long-term treatment in breast cancer. One of the major factor in tamoxifen resistance is overexpression of efflux transporter P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). Curcumin has been known as inhibitor of P-gp and BCRP. The addition of curcumin to tamoxifen resistant cells is expected to increase the sensitivity of breast cancer cells to tamoxifen.

Methods: MCF-7 breast cancer cell line was exposed with tamoxifen 1 µM for 10 passage (MCF-7(T)), then cell viability and mRNA expression of P-gp and BCRP were analyzed. To the MCF-7(T) cells, curcumin of 5, 10, dan 20 µM with or without tamoxifen was given for 5 days and cell viability and mRNA expression of P-gp and BCRP were analyzed on day 2 and 5. As positive control, verapamil 50 µM was used as P-gp inhibitor, ritonavir 15 µM and nelfinavir 15 µM were used as BCRP inhibitor.

Results: The administration of tamoxifen 1 µM for 10 passage (44 days), caused a decreased of MCF-7(T) cells sensitivity to the drug, with 32,08 times reduction in CC50 towards tamoxifen, increased of cell viability of 106,4%, and increased mRNA expression of P-gp and BCRP mRNA of 10,82 and 4,04 fold, respectively. The administration of curcumin with or without tamoxifen for 5 days reduced cell viability and the mRNA expression of P-gp mRNA and BCRP (p < 0,05).

Conclusion: Curcumin increased MCF-7(T) sensitivity to tamoxifen, characterized by decreased of cell viability and mRNA expression of P-gp and BCRP. Increased of sensitivity was estimated at least in part through inhibition of P-gp and BCRP mRNA expression by curcumin. "