Investigating Radiotherapy Effects on PD-L1 Expression in Circulating Tumor Cells: An Exploratory Study.

INTRODUCTION: Circulating tumor cells (CTCs) and Programmed death-ligand 1 (PD-L1) play pivotal roles in cancer biology and therapy response. This exploratory study aimed to elucidate the influence of neoadjuvant radiotherapy on PD-L1 expression in tumor tissues and CTCs of patients with inoperable locally advanced breast cancer. METHODS: We conducted a prospective cohort study at Universitas Andalas Hospital Padang from January to December 2022 with 27 patients. Biopsies and blood draws were executed before and after the tenth fractions of neoadjuvant radiotherapy. Following radiotherapy, CTCs were isolated using magnetic beads enrichment, followed by an RT-PCR analysis for PD-L1 expression. Correlations between PD-L1 expression and tumor response, evaluated via local response and RECIST criteria before and after radiotherapy breast CT scan, were examined using Fisher's exact and chi-square tests. RESULTS: Our data revealed no significant alterations in PD-L1 expression in either tumor tissues or CTCs during radiotherapy (p=0.848 for tissue, p=0.548 for CTCs). Notably, PD-L1 expression in tumor tissue before treatment was significantly associated with RECIST (p=0.021), while other correlations with local response and RECIST were not statistically significant. CONCLUSION: The study implies radiotherapy may not significantly influence PD-L1 expression in tumor tissue and CTCs. However, pre-treatment PD-L1 expression in tumor tissue correlates with RECIST criteria. These findings highlight the need for additional, comprehensive studies to elucidate further the interplay between PD-L1, CTCs, and radiotherapy response.

Sociodemographic disparities associated with advanced stages and distant metastatic breast cancers at diagnosis in Indonesia: a cross-sectional study.

Background: The global health burden of breast cancer is increasing with 5-year survival rates being much shorter in low-income and middle-income countries. Sociodemographic and clinical disparities in early cancer detection affect long-term outcome. Methods: The authors compared social, demographic, and pathological characteristics associated with metastatic and late stages of breast cancer diagnosis using data collected from a special registry developed by Perhimpunan Bedah Onkologi Indonesia (PERABOI) in 2015. Results: Of 4959 patients recruited in this study, 995 women (20.1%) were diagnosed with metastatic breast cancer. Lower education status and living in rural areas were significantly associated with Stage IV at diagnosis [odds ratio (OR)=1.256, 95% CI=1.093-1.445, P=0.001; and OR=1.197, 95% CI=1.042-1.377, P=0.012; respectively). Main complaints other than lump (ulceration, breast pain, and discharge) and occupation as a housewife were also associated with the presentation of metastatic diseases (OR=2.598, 95% CI=2.538-3.448, P<0.001 and OR=1.264, 95% CI=1.056-1.567, P=0.030, respectively). Having lower education and living outside Java and Bali islands were associated with the diagnosis of late-stage breast cancers (OR=1.908, 95% CI=1.629-2.232, P<0.001 and OR=3.039, 95% CI=2.238-4.126, P<0.001; respectively). A higher proportion of breast cancer patients were relatively younger with bigger tumour size, positive axillary nodal involvement, and more frequent Human epidermal growth factor receptor 2 overexpression. Conclusion: The authors identified sociodemographic disparities in the metastatic and late-stage diagnosis of breast cancers among Indonesian women. The subsequent action is required to reduce disparities faced by women with lower social and educational levels for early diagnosis and better healthcare access.

Relationship between the Expression of BRAF V600E and Ki-67 with the Recurrence of Well-Differentiated Thyroid Cancer.

OBJECTIVE: This study aims to determine the relationship between BRAF V600E and Ki-67 expression with the recurrence of well-differentiated thyroid cancers. METHOD: The design of this study is a case-control and survival analysis. The data was taken from the thyroid cancer registry in Padang, Indonesia, where samples were taken from well-differentiated thyroid cancer patients who underwent therapy according to the protocol between 2015 and 2020. During this period, 396 well-differentiated thyroid cancer cases were obtained, of which 24 cases experienced recurrence. Of the cases that recurred, we found as many as 20 cases with complete tissue preservation documents later designated as cases. Calculating the expression of BRAF V600E and Ki-67 was performed semi-quantitatively per 100 tumor cells at random. For statistical tests, chi-square and survival analysis were performed using Kaplan-Meier and Cox regression analysis using a computer program with a determined significance level of p < 0.05. RESULT: BRAF V600E expression was found in all cases and controls in which 85% of cases had vigorous intensity and 15% had moderate intensity. Ki-67 expression was found positive in 35% of the recurrent cases, while in control, there was no expression of Ki-67.  Patients with positive Ki-67 expression had shorter median survival than patients with negative Ki-67 expression of 40 months (95% CI 35-45 months) to 60 months (95% CI 53-67 months). An association was obtained between Ki-67 expression and thyroid cancer recurrence based on disease-free survival (p<0.05) with HR 1.34 (95% CI 1.13-1.92). CONCLUSION: This study confirms the association between Ki-67 expression and thyroid cancer recurrence based on disease-free survival and can be used as alternative to support the significance of Ki-67 as a predictor of thyroid cancer recurrence. In addition, Ki-67 can complement other molecular markers such as the BRAF V600E, to increase its prognostic strength.

ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer.

BACKGROUND: The ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer. METHODS: This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples. RESULTS: The percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05-3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days). CONCLUSION: The ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.

The prioritation and gap of preoperative COVID-19 vaccination in cancer surgery of the breast, head and neck, and skin: A cohort study of 367 patients in an Indonesian hospital.

BACKGROUND: Postoperative infection of Coronavirus Disease 2019 (COVID-19) has been associated with higher risks of mortality and pulmonary complication. Preoperative vaccination could significantly prevent postoperative-related mortality and morbidity particularly for cancer patients. METHODS: Cancer patients who were scheduled for elective major surgery were questioned for status and their willingness to receive COVID-19 vaccination and were prospectively monitored for the presence of postoperative COVID-19 infection and major complications. RESULTS: During the period of April-July 2021, 367 patients with median age of 49 years were scheduled for cancer surgery. Procedures for breast cancer were the most frequently performed (N = 166, 45.2%). Surgery procedures with potential aerosol generating procedures (AGPs) were performed in total of 104 patients (28.3%). Only 6 of 367 patients (1.6%) were fully vaccinated in the day of surgery and 351 patients (95.6%) were willing to receive COVID-19 vaccination. Fully vaccinated patients were significantly higher among those who were living in urban areas (OR = 22.897, 95%CI:4.022-130.357, P = 0.0001). Willingness to get the COVID-19 vaccination was significantly higher among female patients (OR = 4.661, 95%CI:1.685-12.896, P = 0.003). Postoperative COVID-19 infection was confirmed in 17 patients (4.6%) and major surgical complications were observed in 12 patients (3.3%). None of preoperatively vaccinated patients experienced postoperative COVID-19 infection or the related major complications. CONCLUSION: Although prioritizing COVID-19 vaccination in preoperative cancer patients has been recommended to prevent postoperative fatalities, only a small proportion of our patients have been vaccinated. Preoperatively vaccinated patients show advantages in the prevention of postoperative COVID-19 infection and major surgery complications. The slow rollout and disparity in the vaccination progress for patients requiring a major cancer surgery need to be specifically addressed.

Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors.

BACKGROUND: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. METHODS: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014-2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. RESULTS: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071-1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090-2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139-2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035-3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. CONCLUSION: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients' quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.

Pre-treatment neutrophil-lymphocyte and platelet-lymphocyte ratios as additional markers for breast cancer progression: A retrospective cohort study.

BACKGROUND: Breast cancer is the most prevalent cancer that causes significant morbidity and loss of productivity. Around a third of all breast cancer patients are potentially develop distant metastases albeit the current implementation of multidisciplinary treatment. A simple but effective marker to predict the risks of cancer progression is very important for clinicians to improve treatment and surveillance. METHODS: We recruited 1083 non-metastatic patients and analyzed the ratios of neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) in relation to progression-free survivals (PFS) and risks of distant metastases. RESULTS: Baseline clinicopathological variables were not significantly different in the pretreatment NLR and PLRs. Using maximum points of sensitivity and specificity of the Receiver Operating Characteristic (ROC) curve, cut-off values were determined 2.8 for NLR and 170 for PLR. Higher NLR was associated with skin and chest wall cancer infiltration (T4, P = 0.0001). Elevated PLR was associated with more advanced stages at diagnosis (P = 0.03). High NLR values were significantly associated with risks of disease progression (OR 1.555, 95% CI: 1.206-2.005, P = 0.001). Patients with high NLR had shorter PFS (34.9 vs 53.5 months, Log-rank test = 0.001) and shorter time to develop recurrent distant metastatic disease (66.6 vs 104.6 months, Log-rank test = 0.027). CONCLUSION: High NLR is significantly associated with higher risk of disease progression and shorter time to develop metastases particularly among breast cancer patients diagnosed in the advanced stages.

Regional lymph node infiltration and thick lesions are associated with poor prognosis in high-risk resected melanomas: A retrospective cohort study.

BACKGROUND: Acral lentiginous and mucosal melanoma that represent lesions without cumulative sun-induced damages account for 65% of melanomas among Asians but constitute only 5% in Caucasians. The distinct clinical manifestations might influence the clinical course, response to treatment, and outcomes. Factors associated with the prognosis of high-risk resected melanoma in Asians are still rarely reported. METHODS: Clinical, histological determinants of non-distant metastatic melanoma patients who underwent complete resection in 2014-9 were analyzed. RESULTS: Mucosal melanoma, nodular melanoma, and acral lentiginous melanoma accounted for 45.1%, 40.2%, and 14.2% of total melanoma cases (N = 82), respectively. Among cutaneous melanomas, all patients were diagnosed with Breslow's depth more than 4 mm (T4), 51% with ulceration, 95.6% with diameter more than 6 mm, 59% with lympho-vascular invasion, and 74% with regional lymph node infiltration. In mucosal melanomas, 78.3% were diagnosed in advanced stages, 14.5% with regional spread to lymph nodes and 77% with regional infiltration beyond mucosa. Lesions with ulceration were associated with higher risk of distant metastasis (OR 3.003, 95%CI:1.01-9.09). Infiltration into regional lymph node was associated with shorter overall survival (median survivals were 17 vs 23.4 months, Mantel-Cox test P = 0.049). Patients diagnosed at Breslow T4 were also associated with poorer overall survival than T1-3 (median survivals were 23 vs 32 months, Mantel-Cox test P = 0.047). CONCLUSION: The majority of melanoma patients in our population were diagnosed in advanced stages with a higher risk for recurrence and progression into distant metastasis. Regional lymph node involvement and thicker tumor (T4) were associated with poor prognosis.

Complete diaphysis resorption of the femur: A case report in a metastatic papillary thyroid cancer.

INTRODUCTION: Although differentiated thyroid cancers generally have a good prognosis, a small proportion of patients will have recurrent or progressive disease. Bone resorption due to thyroid cancer can cause significant challenges in the clinical management and rehabilitation. PRESENTED CASE: Nearly total femur resorption was found as a first presentation in a patient with thyroid cancer. The patient complained about chronic pain in her left thigh that had progressed into an inability to walk. She was treated by a traditional healer for six years before she was persuaded by a social worker to seek medical help. X-rays showed pathological loss of the right diaphyseal femur. Neck CT-scan showed a left thyroid mass with tracheal deviation, with multiple lytic lesions in the sternum and 5th rib. Needle biopsy of the thyroid mass resulted in an inconclusive follicular neoplasm. Total thyroidectomy and neck dissection revealed a classical type of papillary thyroid carcinoma. After thyroid ablation, she opted for palliative radiotherapy and bisphosphonate treatment for the bone metastases. DISCUSSION: Bone metastases are rarely detected at the time of thyroid cancer diagnosis. In the presence of bone metastasis, median survival of well-differentiated thyroid cancer decreases into only 4 years. Bone metastases are often neglected and less studied than regional lymph node and lung metastases. CONCLUSION: Although well differentiated thyroid cancer is usually indolent, a neglected bone metastasis at an initial diagnosis might adversely affect patient's quality of life and prognosis.

Clinical characteristics and the associated risk factors of the development of bilateral breast cancers: A case-control study.

BACKGROUND: The clinical impacts of bilateralism on prognosis and clinical decision-making remain contradictory particularly in areas with low incidence and delayed diagnosis of primary breast cancer. Identification of women at risk of bilateral breast cancer is required to improve patient management and to design the appropriate surveillance. METHODS: A total of 1083 women were enrolled and analyzed for the presence of synchronous and metachronous bilateral breast cancer as cases and unilateral breast cancer as controls during the median follow-up of 4.8 years. RESULTS: The incidence of bilateral breast cancer was 7.5% (81 of 1083). In comparison with unilateral breast cancers, bilateral cases were significantly diagnosed in younger women (P = 0.037, mean age was 35.6 years) who had a larger tumor size (P = 0.012, mean tumor size was 8 cm in diameter). Histological type of lobular cancer was identified as one of the risk factors for the development of contralateral breast cancer (OR 5.564, 95% CI: 3.219-9.620) and synchronous bilateral breast cancer (OR 2.561, 95% CI: 1.182-5.550). Bilateral breast cancer had significantly shorter progression-free survival (Mean survival was 26.6 vs 52.5 months for bilateral and unilateral breast cancers, respectively; P = 0.001) and shorter time to develop distant metastasis (Mean survival was 41.7 vs 104 months for bilateral and unilateral breast cancers, respectively; P = 0.001). CONCLUSION: Patients with first primary breast tumors with lobular histological type and advanced stages were observed to have higher risks for the development of contralateral breast cancers.

Survey data of multidrug-resistant tuberculosis, Tuberculosis patients characteristics and stress resilience during COVID-19 pandemic in West Sumatera Province, Indonesia.

This set of data presents a survey data describing multidrug-resistant tuberculosis, tuberculosis patients characteristics and stress resilience during COVID-19 pandemic in West Sumatera Province, Indonesia. The data were gathered from multidrug-resistant tuberculosis, tuberculosis patients through a survey distributed by an online questionnaire, assesing patients characteristics (age, sex, level of education, working status, history of close contact to patients with multidrug resistant tuberculosis and tuberculosis, smoking, alcohol consumption, cavitary pulmonary, diabetes mellitus, nutritional status and tuberculosis outside the lung) and stress resilience (3 items), from 15th July until 7th August 2020. The samples were collected 73 multidrug resistant tuberculosis patients and 219 tuberculosis patients in West Sumatera Province, Indonesia who were willing to fill an online questionnaire. SPSS version 23.0 was used to analyzed the data by descriptive and inferential statistics. The data will help to identify mental health problems and potentially as a warning sign that can support for health education interventions among multidrug-resistant tuberculosis and tuberculosis patients during COVID-19 pandemic.

Survey data of COVID-19 awareness, knowledge, preparedness and related behaviors among breast cancer patients in Indonesia.

This dataset presents a survey data describing COVID-19 awareness, knowledge, preparedness and related behaviors among breast cancer patients in Indonesia. The data were collected from breast cancer patients through a survey distributed by an online questionnaire, assesing social-demographic characteristics (6 items), COVID-19 awareness (5 items), knowledge (2 items), preparedness (2 items) and related behaviors (2 items), from 20th June until 14th July 2020. The samples were gathered 500 breast cancer patients in Indonesia who were willing to fill an online questionnaire. SPSS version 23.0 was used to analyzed the data by descriptive and inferential statistics and SmartPLS 3 to created the partial least square path modeling. The data will help in preventing the transmission of COVID-19 among breast cancer patients and can support for health education and promotion interventions.

Risk factors of distant metastasis after surgery among different breast cancer subtypes: a hospital-based study in Indonesia.

BACKGROUND: More than one third of breast cancer patients including those that are diagnosed in early stages will develop distant metastasis. Patterns of distant metastasis and the associated risks according to the molecular subtypes are not completely revealed particularly in populations of patients with delayed diagnosis and advanced stages. METHODS: Breast cancer patients (n = 1304) admitted to our institute (2014-2017) were evaluated to identify the metastatic patterns and the associated risks. Metastatic breast cancers at diagnosis were found in 245 patients (18.7%), and 1059 patients were then grouped into non-metastatic and metastatic groups after a median follow-up of 3.8 years. RESULTS: Infiltration of the tumor to the skin and chest wall prevailed as the most powerful predictor for distant metastasis (OR 2.115, 95% CI 1.544-2.898) particularly in the luminal A-like subtype (OR 2.685, 95% CI 1.649-4.371). Nodal involvement was also significantly associated with the risk of distant metastasis (OR 1.855, 95% CI 1.319-2.611), and the risk was higher in the Luminal A-like subtype (OR 2.572, 95% CI 1.547-4.278). Luminal A-like subtype had a significant higher risk of bone metastasis (OR 1.601, 95% CI 1.106-2.358). In respect to treatment, a combination of anthracyclines and taxanes-based chemotherapy was significantly associated with lower distant organ spread in comparison with anthracycline-based chemotherapy (OR 0.510, 95% CI 0.355-0.766) and the effect was stronger in Luminal A-like subtype (OR 0.417, 95% CI 0.226-0.769). Classification into Luminal and non-Luminal subtypes revealed significant higher risks of bone metastasis in the Luminal subtype (OR 1.793, 95% CI 1.209-2.660) and pulmonary metastasis in non-Luminal breast cancer (OR 1.445, 95% CI 1.003-2.083). CONCLUSION: In addition to guiding the treatment plan, a comprehensive analysis of clinicopathological variables including the molecular subtypes could assist in the determination of distant metastasis risks of breast cancer patients. Our study offers new perspectives concerning the risks of distant metastasis in breast cancer subtypes in order to plan intensive surveillance or escalation of treatment particularly in a setting where patients are predominantly diagnosed in late stages.

Perspectives on how to navigate cancer surgery in the breast, head and neck, skin, and soft tissue tumor in limited-resource countries during COVID-19 pandemic.

The rapidly spreading coronavirus infection (COVID-19) worldwide has contracted all aspects of health systems. Developing countries that mostly have a weaker healthcare system and insufficient resources are likely to be the most hardly affected by the pandemic. Cancers are frequently diagnosed in late stages with higher case-fatality rates compared to those in high-income countries. Delayed diagnosis, lack of cancer awareness, low adherence to treatment, and unequal or limited access to treatment are among the challenging factors of cancer management in developing countries. Elective cancer surgeries are often considered to be postponed during COVID-19 pandemic to preserve valuable hospital resources such as personal protection equipment, hospital bed, intensive care unit capacity, and manpower to screen and treat the affected individuals. However, specific considerations to defer cancer surgery in developing countries might need to be carefully adjusted to counterbalance between preventing COVID-19 transmission and preserving patients 'long-term life expectancy and quality of life.

Analysis Natrium Iodide Symporter Expression in Breast Cancer Subtypes for Radioiodine Therapy Response.

PURPOSE: This study investigates natrium iodide symporter (NIS) expression in three breast cancer subtypes to predict radioiodine response. MATERIALS AND METHODS: Frozen breast tissues from triple negative (TN), human epidermal receptor 2 (HER2+), and luminal A cancers were used in this research. NIS protein expression in each subtype was analyzed using immunohistochemistry (IHC) and western blot (WB). Secondary data such as age, subtypes, and Ki 67 index were drawn from the surgical oncologist database. Breast cancer cell lines were used to investigate the effect of radioiodine by measuring cell proliferation. RESULTS: The forty-one breast cancer samples were analyzed consisted of the following subtypes: TN, HER2+, and luminal A were 58%, 22%, and 20% respectively. The stages of disease were 2A to 4A. Most of samples were at 3B. Ki 67 index of TN, HER2+, and luminal A were 21 ± 12, 19 ± 5, and 7 ± 3 respectively. The NIS expression was detected in 95% of samples in cytoplasm and/or cell membrane; 93% of samples were invasive breast carcinomas. Only 20% of the samples showed NIS expression at cell membrane; four samples were HER2+, and other four were TN subtypes. NIS membrane score was significantly positively correlated with Ki67 index, p = 0.04. NIS protein expression was detected at sizes 88 kDa, 50 kDa, and 27 kDa. Cell proliferation rate means of MDA-MB 231, SKBR3, and MCF7 cells were 81.6 ± 4, 10.6 ± 5, and 15.4 ± 13 respectively (p = 0.009). CONCLUSION: NIS protein expression is detectable in breast cancer cells to varying degrees. HER2+ is the most likely to express NIS in the cell membrane followed by TN subtypes. This indicates that radioiodine could be used as a novel adjuvant treatment in breast cancer.

The Comparison of RhoC and PI3K Gene Expression on the Breast Cancer Tissue and Benign Tumour Tissue.

BACKGROUND: The expression of a gene is a process that conveys information of genes to synthesise gene product is functional. Alterations of the molecular biology in breast cancer are very complex because of many factors play a role in the tumorigenesis. RhoC is a prometastases gene. The PI3K gene is crucial in the regulation of multiple cellular functions, including cell growth, proliferation, metabolism and angiogenesis. AIM: This study aims to compare of RhoC and PI3K gene expression on the breast cancer tissue and benign tumour tissue. MATERIAL AND METHODS: Expression of the RhoC and PI3K genes was carried out with qPCR. The absolute quantification method was using breast cancer tissue. As a comparison, benign tumours (FATs) tissue was carried out. The standard curves were obtained from cloning target genes, which were inserted into the gGEMT-easy vector from E. coli. The gene expression data was carried out by t-test to see the mean difference between the expression of breast cancer tissue and benign tumours (FATs) with a value of p ≤ 0.005 in RhoC and PI3K gene expression. And the relationship between expressions was done by Pearson correlation test. RESULTS: The results showed that it was found that PI3K gene expression on breast cancer tissue was higher than the number in a benign tumour (fibroadenoma mammae) as an endogenous control. And also, the expression of RhoC is much lower on breast cancer tissue compared with a benign tumour. CONCLUSION: This study concluded that expression of RhoC affects the expression of PI3K so that the thing this is what causes the proliferation and began to provide support aggressive cancer cells in the breast.

Prognostic Factors of Local-Regional Recurrence in Patients with Operable Breast Cancer in Asia: A Meta-Analysis.

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.

Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study.

BACKGROUND: Breast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia. METHODS: We analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012-2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics. RESULTS: From the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05). CONCLUSION: We found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.

The Prognostic Significance of Phosphatase and Tensin Homolog Loss in Breast Cancer.

AIM: This study aims to determine the prognostic significance of phosphatase and tensin homolog (PTEN) loss in breast cancer. METHODS: We conducted a meta-analysis study. Sample of this study were research articles that evaluated PTEN loss and prognosis in breast cancer patients. We searched for relevant studies published in PubMed and Proquest from January 2010 to July 2018. We reviewed studies that examined the association between immunohistochemical expression of PTEN and breast cancer prognosis using meta-analysis methods. Pooled risk ratios (RR) were calculated using fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). RESULTS: There were 7 studies conducted a systematic review then continued to evaluate the association of PTEN loss and breast cancer prognosis by meta-analysis. There was a significant association of PTEN loss with poor prognosis of breast cancer (RR = 0.76 [95% CI 0.59-0.98 p <0.07), and there was not any significant publication bias for studies included. CONCLUSION: This study confirmed PTEN loss is an important independent factor for breast cancer prognosis.

BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadic Breast Cancer Patients in Indonesia

Objective: The aim of this study was to investigate the BRCA1 promoter methylation and clinicopathological characteristics in sporadic breast cancer patients in Indonesia. Methods: In this cohort study, we selected 90 patients with stage I-III who had definitive surgery at our institution in 2011-2014. Demographic and clinical data regarding pathological stage, breast cancer treatment, outcome etc. were collected from the medical records. Twelve patients had incomplete information on follow up and 18 samples had insufficient tissues for the experiment. Sixty patients with adequate cancer tissues and complete follow up record were analyzed, only 56 patients were analyzed because 4 samples mRNA expression could not be detected. The Mann­Whitney U tests for non-normally distributed groups were used to compare the levels expression of BRCA1 mRNA between methylated and non-methylated samples. Chi-square tests were used to compare methylation status, BRCA1 mRNA expression and clinicopathological characteristics. P value < 0.05 was considered as statistically significant correlation. Data analysis was held by using the GraphPad PRISM 7 (GraphPad Software Inc., USA). Results: DNA and RNA were isolated from primary tumor tissues of 56 breast cancer patients. BRCA1 promoter methylation was detected in 48 of 56 patients (85%). Level of BRCA1 mRNA expression was associated with decreased methylation level in the BRCA1 promoter regions suggesting the role of epigenetic silencing. However, there was no statistically significant association among methylation levels, BRCA1 mRNA transcript level with clinicopathological factors. Conclusion: To our knowledge, this is the first study investigating methylation status and level of BRCA1 mRNA transcripts among breast cancer patients in Indonesia. We found that the prevalence of BRCA1 promoter methylation is higher than other studies from different populations. However, further investigation involving larger number of patients is required.