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INDONESIA
Indonesian Journal of Cancer
Published by National Cancer Center-Dharmais Cancer Hospital
ISSN : 19783744     EISSN : 23556811     DOI : https://www.doi.org/ 10.33371
Core Subject : Health, Science,
Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Public Health
Indonesian Journal of Cancer is a peer-reviewed and open-access journal. This journal is published quarterly (in March, June, September, and December) by Dharmais Cancer Hospital - National Cancer Center. Submissions are reviewed under a broad scope of topics relevant to experimental and clinical cancer research. Articles are original research that needs to be disseminated and written in English. All submitted manuscripts will go through the double-blind peer review and editorial review before being granted acceptance for publication. The journal publishes original research articles, case reports, and review articles under the following categories: cancer management, cancer prevention, cancer etiology, epidemiology, molecular oncology, cancer diagnosis and therapy, tumor pathology, surgical oncology, medical oncology, radiation oncology, interventional radiology, as well as early detection.
Arjuna Subject : Kedokteran - Onkologi
Articles 26 Documents
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Search results for , issue "Vol 20, No 1 (2026): March" : 26 Documents clear
Risk Factors and Infection Patterns of Febrile Neutropenia after Induction Chemotherapy in Patients with Acute Myeloid Leukemia Pratiwi, Made Sindy Astri; Agustini, Made Priska Arya; Rena, Ni Made Renny Anggreni; Bakta, I Made
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1495

Abstract

Background: Febrile neutropenia (FN) is a serious cause of mortality in acute myeloid leukemia (AML), with a mortality rate of 10-30%. FN often occurs after receiving induction chemotherapy in AML. Patients with FN are susceptible to various infections, but the pathogens are often unknown. It is important to predict FN and identify the specific pathogen of infection. This study aims to identify risk factors and infection patterns of FN after induction chemotherapy in AML patients.Methods: This research was a retrospective cohort study located at Prof. I.G.N.G Ngoerah General Hospital, Bali. The samples were AML patients aged ≥ 18 years treated with induction chemotherapy, cytarabine plus daunorubicin, from 2018 to 2022. The risk factors assessed were age, gender, body mass index, ECOG status, comorbidity, and pre-treatment blood count. The patients who had FN would be assessed for the incidence of infection through microbiological examination.Results: This study included 92 patients aged 19 to 76 years old. As many as 68 patients (73.9%) had FN. A multivariate analysis showed ECOG status (p = 0.004; OR 6.680; 95% CI 1.830 – 24.385), comorbidity (p = 0.010; OR 7.394; 95% CI 1.628 – 33.575), and haemoglobin level ≤ 8 g/dL (p = 0.015; OR 6.043; 95% CI 1.449 – 33.265) as significant risk factors. The most common site of infection was the respiratory tract (63.75%), followed by genitourinary (15%) and skin (8.75%). Most specimens were obtained from sputum (35%), blood (26.25%), and urine (15%). Streptococcus sp., Staphylococcus sp., and Escherichia coli were the top three most common pathogens found. Conclusions: ECOG status, comorbidity, and low haemoglobin level were associated with FN after induction chemotherapy of AML. Patients with FN are susceptible to various infections. The identification of risk factors and infections of FN will facilitate consideration of further treatment in AML.
The Relationship of Immunohistochemical Expression of BRAFV600E with Clinical Features and Histopathological Subtypes in Papillary Thyroid Carcinoma (PTC) Masriana, Masriana; Betty, Betty; Delyuzar, Delyuzar; Alferraly, Ibnu; Dahlan, Nadjib
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1434

Abstract

Background: Papillary thyroid carcinoma (PTC) is an indolent thyroid malignancy with clinicopathological features that play a role in prognosis. BRAFV600E mutations in PTC are associated with poor prognosis, and BRAFV600E immunohistochemical staining exhibits high specificity and sensitivity. This study aims to determine the association between BRAFV600E immunohistochemical expression and clinical features and histopathological subtypes in PTC.Method: This analytical observational study utilizes a cross-sectional approach, conducted from March to December 2024 at the Anatomical Pathology Laboratory, Faculty of Medicine, Universitas Sumatera Utara, and affiliated hospitals. A total of 35 PTC samples were selected and continued with BRAFV600E immunohistochemical staining. Clinicopathological data, including age, gender, tumor size, lymph nodes, metastasis, lymphovascular invasion, disease stage, and PTC subtype, were collected. Statistical analysis was performed using Somers'd (ordinal-ordinal) and Eta (nominal-ordinal) correlation test in SPSS.Results: PTC was most prevalent among females and the age group under 45 years. Predominant clinical features included tumor sizes exceeding 4 cm (T3), an absence of lymph node involvement (N0), and no detectable metastasis (M0). The classic subtype emerged as the most frequent histopathological variant, typically presenting without lymphovascular invasion (LVI) and diagnosed at Stage I. While most parameters showed no significant statistical association with BRAFV600E expression (p 0.05), a significant relationship was identified specifically regarding the cancer stage (p 0.05).Conclusion: There are no significant associations observed between BRAFV600E immunohistochemical expression and the majority of clinicopathological factors. However, a significant relationship with disease stage was identified. These findings suggest that BRAFV600E expression may have potential value as an indicator of disease stage in PTC.
Integrating Molecular, Digital, and Morphological Insights: The Unavoidable Future of Oncologic Diagnostics Hasibuan, Arie Widiansyah; Delyuzar, Delyuzar
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1620

Abstract

The remarkable progress of Anatomical Pathology over recent decades has fundamentally reshaped the landscape of oncologic diagnostics. From the early era when microscopic interpretation of routine hematoxylin-eosin (HE) stained sections formed the diagnostic cornerstone, the discipline has evolved into a complex hub of integrated biological data. This journey began with mastery of histopathological and cytological morphology and expanded to the use of histochemical and immunohistochemical stains, enabling precise visualization of specific proteins. The transformation continued as molecular technologies became routinely implemented in major laboratories, extending diagnostic capacity far beyond the limits of the optical microscope [1]. Advances in molecular techniques have opened a new dimension in cancer understanding. Polymerase chain reaction (PCR), real-time quantitative PCR, and reverse transcription PCR enable highly sensitive detection of gene mutations or transcripts, including EGFR mutations in pulmonary adenocarcinoma and BCR-ABL fusion transcripts in leukemia. Fluorescence in situ hybridization (FISH) adds the ability to visualize gene amplification or chromosomal rearrangements directly within cell nuclei, for example, to confirm HER2 amplification in breast carcinoma or ALK rearrangements in lung carcinoma. The most dramatic leap has come with next-generation sequencing (NGS), which uses massively parallel sequencing. It can interrogate hundreds to thousands of genes simultaneously. Targeted gene panels, whole-exome sequencing, and even whole-genome sequencing facilitate identification of driver mutations, copy number variations, and gene fusions in a single analysis. Tumor mutational burden and microsatellite instability status have now been recognized as critical biomarkers in selecting patients for immunotherapy. Moreover, transcriptomics, proteomics, and metabolomics, collectively referred to as “omics”, provide comprehensive insight into the interplay of genes, proteins, and metabolites that govern tumor biology and allow detection of germline mutations for familial risk assessment. The emergence of liquid biopsy, through analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), adds the ability to dynamically monitor the development of resistance mutations and therapeutic response without invasive procedures [1,2]. At the same time, digital technologies and artificial intelligence (AI) are revolutionizing the practice of pathology. Digital pathology using whole slide imaging (WSI) replaces glass slides with high-resolution digital files that can be stored, shared, and algorithmically analyzed. Deep-learning algorithms are now capable of highlighting tumor areas, quantifying proliferation indices such as Ki-67, and even predicting genetic mutations directly from HE images. Integration of AI not only accelerates diagnosis and reduces interobserver variability but also transforms histomorphologic images into quantitative data that can be correlated with clinical outcomes. These developments reposition the pathologist from a mere “slide reader” to an integrator of biological information combining morphology, molecular data, and digital analytics [2–5,7]. Despite the force of these innovations, morphology remains an irreplaceable foundation. Evaluation of tissue architecture in histopathology and cytology, and the recognition of growth patterns, continue to provide essential biological context that cannot be fully supplanted by genomic data. Histologic grading systems such as Nottingham for breast carcinoma and Gleason for prostate carcinoma remain critical determinants of risk stratification and therapeutic planning. Assessment of surgical margins, selection of representative tumor areas for further molecular analysis, and correlation with radiologic findings require the pathologist’s expertise as curator of tissue. Without quality control anchored in microscopic evaluation, molecular results risk being misleading [1]. Thus, the prediction that “pathologists will abandon the microscope” is only literally true because optical devices may be replaced by WSI monitors. It does not signify abandonment of morphological analysis itself [3–5]. This paradigm shift carries broad implications for every branch of oncology. Medical oncologists rely on molecular findings to guide targeted therapy; surgeons require accurate information to determine resection margins; and genetic counselors assess familial risk based on germline alterations. The concept of “integrated diagnosis” emphasized in the 5th edition of the World Health Organization classification of tumors provides the modern framework: the final diagnosis synthesizes morphology, immunohistochemistry, and molecular data into a single comprehensive report [1]. Contemporary cancer therapy decisions from the selection of tyrosine kinase inhibitors to checkpoint inhibitor immunotherapy can only be reached through such multidimensional interpretation [2]. Adoption of these advanced technologies demands robust infrastructure, significant financial investment, and personnel with bioinformatics expertise. Disparities between major referral centers and regional hospitals must be addressed so that progress does not widen gaps in cancer care. Issues of genomic data privacy, clinical validation of analytic pipelines, and legal responsibility for AI-assisted decisions require careful attention. Governments, educational institutions, and hospitals must invest in molecular pathology and bioinformatics curricula and prepare appropriate regulatory frameworks [7]. Anatomical Pathology is now entering an era in which the role of the pathologist has shifted from mere microscopic examiner to architect of integrated cancer biology data. The strengths of NGS, FISH, advanced PCR, omics, and liquid biopsy have opened new perspectives on cancer pathogenesis, precision therapy, and dynamic disease monitoring. Yet these advances do not diminish the role of morphology; rather, they reinforce its status as the foundation upon which molecular analysis and AI applications depend [1-5,7]. All oncology stakeholders must work together to build infrastructure and collaborative networks so that cancer services in Indonesia are fully prepared for the era of precision diagnostics, where molecular, digital, and morphological integration becomes the gold standard of modern cancer management.
The Role of Tumor-Infiltrating Lymphocytes in Ovarian Cancer Prognosis: A Systematic Review on Immune Subtypes and Spatial Distribution Kusumastuti, Sanindita; Hellyanti, Tantri; Kodariah, Ria
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1433

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) are key components of the immune microenvironment in ovarian cancer, influencing disease progression and clinical outcomes. However, the prognostic significance of different TIL subtypes, including CD8+, CD4+, FOXP3+ regulatory T cells, and CD20+ B cells, remains inconsistent across studies. This systematic review aims to synthesize current evidence on the prognostic roles of these immune subtypes, with a focus on their spatial distribution within the tumor microenvironment and associations with overall survival (OS) and progression-free survival (PFS) in ovarian cancer. Methods: A systematic search was conducted using the PRISMA 2020 guideline protocol and was registered under PROSPERO with registration number CRD42025638744. Several databases, including PubMed, Scopus, and Google Scholar, were included to obtain articles, using keywords related to ovarian cancer, TILs, immune subtypes, and prognosis. Studies published in peer-reviewed journals without time restrictions were included. Selection criteria focused on studies that reported the density and localization of TIL subtypes and their association with clinical outcomes.Results: Fifteen studies met the inclusion criteria, involving 7,982 ovarian cancer patients. CD8+ TILs, together with CD20+ B cells and memory T cells, were consistently associated with better clinical outcomes, particularly when localized within intraepithelial regions. CD4+ T cells exhibited diverse prognostic effects depending on their polarization, where FOXP3+ regulatory T cells were linked to poor prognosis due to their immunosuppressive functions. The spatial distribution of TILs was a critical determinant of their prognostic value, with intraepithelial TILs showing stronger anti-tumor activity than stromal TILs. Variability in detection methods, cut-off values, and tissue sampling contributed to inconsistencies across studies.Conclusion: While TILs phenotypes may predict clinical outcome in ovarian cancer patient, their spatial distribution must be taken into consideration to sharpen analysis. To establish a more reliable prognostic marker, methodologies using standardized TIL thresholds should be implemented, hence the need for further studies.
Periorbital Necrotizing Fasciitis in Lung Adenocarcinoma Patient Receiving Afatinib: A Case Report Kusumawardani, Ida Ayu Jasminarti Dwi; Tan, Leviani; Indraswari, Putu Gita; Yuliawati, Putu; Wiradana, A.A. Gde Agung Anom Arie
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1417

Abstract

Background: Afatinib is a second-generation Tyrosine Kinase Inhibitor (TKI) approved by the Food and Drug Administration (FDA) as first-line therapy for advanced Non-small cell lung cancer (NSCLC) with distant organ metastasis. However, afatinib has been reported to cause several side effects. Here, we report a case of periorbital necrotizing fasciitis, potentially associated with afatinib use, presenting as a grade 3 side effect in a 59-year-old woman with stage IVB lung adenocarcinoma. This is the first literature reporting afatinib-related periorbital necrotizing fasciitis, a rare sight-threatening infection.Case Presentation: A 59-year-old female patient came to the Emergency Room with a protruding left eye, which is accompanied by redness, purulent discharge, and a blackish wound around the left eye area for the last 5 days. The patient had been diagnosed with stage IVB lung adenocarcinoma (T4N3M1c) six months ago. Previously, she underwent chemotherapy with a combination of Gemcitabine and Carboplatin. The patient then underwent 20 cycles of radiotherapy followed by immunotherapy using afatinib. The patient was then admitted with suspected necrotizing fasciitis of the left periorbital area due to side effects of afatinib. She was given ceftriaxone 2 grams every 24 hours intravenously (IV), analgesics IV, methylprednisolone IV, gentamicin eye drops, and regular wound care. After several days of treatment, the patient had significant improvement. Afatinib therapy was temporarily stopped. Re-evaluation at one month showed significant improvement in the patient's left periorbital area. Afatinib therapy was then continued at a lower dose of 30 mg every 24 hours.Conclusions: Good education and caution are still needed for patients who were given afatinib. More studies on the side effects of afatinib are needed to identify predisposing factors and establish a consensus on the management of afatinib-induced periorbital necrotizing fasciitis in NSCLC patients.
The Effect of Hyperbaric Oxygen Therapy on Neutrophil to Lymphocyte Ratio (NLR) in Wistar Strain Female White Rats (Rattus norvegicus) Induced by 7,12-dimethylbenz[a]anthracene (DMBA) Mangkuluhur, Ande; Sudiarta, Ketut Edy; Nefertiti, Eva Pravitasari
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1406

Abstract

Background: Tumors are caused by uncontrolled cell growth, and the immune system plays a crucial role in this process. Neutrophils and lymphocytes are key immune cells involved in tumor behavior. Adenosine and its A2 receptor can activate neutrophils to promote inflammation that may lead to tumor growth. In contrast, lymphocyte especially cytotoxic T cells, can attack and kill tumor cells, helping to reduce tumor growth and inflammation. This study explores how hyperbaric oxygen therapy (HBOT) can influence the neutrophil-to-lymphocyte ratio (NLR) in female Wistar rats exposed to a known carcinogen, 7,12- dimethylbenz[a]anthracene (DMBA).Method: The research followed a post-test-only control group design. Two control groups were established: one that received a normal diet and the other that was treated with DMBA at a dosage of 20 mg/kgBW for four weeks. The treatment group received both the carcinogen and HBOT at 1.7 Atmospheric Absolute for 30 minutes, three times daily for five days. Blood samples were taken, and the NLR was measured using IBM SPSS software version 26. Result: Results showed significant differences in NLR among the groups. The negative control group had a mean NLR of 1.3444, the positive control group had 3.7889, and the treatment group had 1.6889. A statistically significant difference in these mean NLR values (p = 0.000) was observed among Female Wistar Rats subjected to the effects of the carcinogen DMBA combined with HBOT. Conclusion: The study concluded that HBOT significantly reduced NLR values in these rats exposed to the carcinogen. These findings highlight the potential of HBOT as a supportive therapeutic intervention in modulating the tumor-associated immune environment.
Global Research Trends on Ablation for Hepatocellular Carcinoma: Insights from A Comprehensive Bibliometric Analysis and Visualization Athoillah, Nabil; Hibatullah, Muhammad Naufal; Buaji, Brilliantara; Rayyan, Muhammad Isra; Febriakhano, Aji
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1443

Abstract

Background: Ablation has been intensively studied as an effective and minimally invasive management for hepatocellular carcinoma (HCC). Plenty of publications have been written in the last century about ablation in HCC, but no bibliometric analysis has comprehensively analyzed the topic of ablation in HCC. This study aimed to explore the recent development of HCC ablation using bibliometric analysis. Methods: Publication data were comprehensively retrieved from the Scopus database using total sampling technique from the first publication to August 3, 2024. Then, the data were analyzed and visualized using VOSviewer and RStudio software to reveal publications per year, most frequently occurring keywords, most productive authors and countries, article citations, and international collaborations.Results: Thirteen thousand, nine hundred fifty-five publications were extracted from the Scopus database between 1950 and 2024. The research trend on ablation and HCC has increased massively, especially since 1999. China and the World Journal of Hepatology were identified as the most productive countries and journals in this field. In addition, Kudo Masatoshi has 187 articles and is the most influential researcher in this field. The bibliometric data illustrated that the most frequently reviewed ablation modality was radiofrequency ablation, followed by microwave ablation, percutaneous ethanol injection, and high-intensity focused ultrasound. In addition, the bibliometric analysis showed that recent ablation research trends favored microwave ablation and high-intensity focused ultrasound as ablation techniques, using efficacy and safety parameters as primary outcomes. Meta-analysis is a research method related to ablation that has primarily been conducted recently. Ablation modalities are also frequently studied simultaneously with immunotherapy, systemic, and locoregional modalities.Conclusions: Current research on HCC ablation continues to increase, with study trends shifting from percutaneous ethanol injection and radiofrequency ablation to microwave ablation and high-intensity focused ultrasound. Meta-analysis and efficacy-safety are essential research methods and outcomes to review.
Transarterial Embolization as a First-Line Treatment for Ruptured Renal Angiomyolipoma: A Case Report Wicaksono, Krishna Pandu
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
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Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1534

Abstract

Introduction: Angiomyolipoma (AML) is a benign renal tumor that can be accompanied by potentially life-threatening spontaneous retroperitoneal hemorrhage when it becomes large. Prompt management is crucial. Treatment options for ruptured renal AML include surgical intervention and embolization, with transarterial embolization (TAE) increasingly recognized for its renal-sparing advantage and reduced invasiveness. We describe a case effectively managed with emergency TAE, highlighting its safety and efficacy.Case Presentation: A 57-year-old male was admitted for evaluation of hematuria, right flank pain, abdominal distension, and dyspnea. His condition was complicated by severe anemia and declining renal function, with eGFR of 28.1 mL/min/1.73 m². CT-scan angiography demonstrated a large retroperitoneal hematoma and a pseudoaneurysm, 3.5 × 4.0 × 6.0 cm, at the upper pole of the right kidney, arising from an interlobar artery. Multiple bilateral angiomyolipomas were also shown. An emergency transarterial embolization was performed using polyvinyl alcohol (PVA) particles to devascularize hypervascular lesions and detachable coils to occlude the pseudoaneurysm. Further embolization was also performed in the mid-segment, resulting in the complete resolution of lesions while maintaining the functional renal parenchyma. Clinical improvement was evident during a two-day follow-up, as indicated by an increase in hemoglobin levels, resolution of hematuria, and relief of abdominal symptoms.Conclusion: This case supports the role of TAE as an effective and organ-preserving treatment for ruptured renal AML.
Correlation of Overexpression of PDL-1 With Lymph Node Metastasis in Penile Carcinoma Witari, Ni Putu Diah; Analysa, Analysa; Lestari, Putu Oki
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1360

Abstract

Background: Penile cancer cases are rarely found, but in the Bali area, the case is higher than in other regions in Indonesia. The death rate of penile cancer is still high, and 80% of cancer deaths are related to metastasis. As immunotherapy in cancer develops, PDL-1 is becoming one of the targets for immune therapies that promise to replace conventional therapies or serve as adjunct therapies. This study aims to see the correlation between the overexpression of PDL-1 and lymph node metastasis, which is one indicator of the poor prognosis of a cancer.Methods: This study used a case-control study design with a retrospective approach. The sample was 70 primary squamous type penile cancer formalin-fixed paraffin-embedded (FFPE) specimens with complete clinical data from several Anatomic Pathology laboratories in Bali, 2015-2023. FFPE sections that were damaged and did not have complete data were excluded. The case is 35 with lymph node metastasis, and 35 without lymph node metastasis as a control. In this study, the correlation between PDL-1 overexpression and tumor grading and lymph node metastasis in penile carcinoma will be explored. Data analysis with Chi-square using SPSS. The p-value for the significance test was less than 0.05. The accuracy of the data is determined by a 95% confidence interval (CI). The research was conducted from February 2024 to August 2024 Results: This study showed a significant correlation between PDL-1 overexpression and lymph node metastasis, p 0.05. There was a significant correlation of PDL-1 overexpression with lymph node metastasis (p = 0.001). There was a correlation between overexpression of PDL-1 and tumor size (p = 0.035), tumor grading (p = 0.027), and lymphatic invasion (p = 0.038). There was no correlation between PDL-1 overexpression with age (P = 0.424)Conclusions: This study demonstrates a significant correlation between PDL-1 overexpression and lymph node metastasis in penile carcinoma patients. Furthermore, PDL-1 overexpression is significantly associated with larger tumor size, higher tumor grade, and lymphatic invasion. These results suggest that PDL-1 serves as a critical prognostic biomarker for predicting disease aggressiveness and metastatic potential.
The Potential of Lasofoxifene as a New Hormone Therapy Targeting ESR1 Mutations in ER+ Breast Cancer Patients: A Narrative Review Abidin Shahab, Ali Zainal; Darmayanti, Salma
Indonesian Journal of Cancer Vol 20, No 1 (2026): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v20i1.1423

Abstract

Breast cancer remains the most prevalent malignancy among women and a leading cause of cancer-related mortality worldwide. Estrogen receptor-positive (ER+) breast cancer accounts for the majority of breast cancer cases, with hormonal therapy being the primary treatment approach. However, resistance to conventional endocrine therapy, particularly due to mutations in the estrogen receptor 1 (ESR1) gene, poses a significant challenge. ESR1 mutations, especially in the ligand-binding domain, lead to ligand-independent activation of the receptor, rendering standard therapies ineffective. Lasofoxifene, a selective estrogen receptor modulator (SERM), has emerged as a promising alternative for ER+ breast cancer patients with ESR1 mutations. Preclinical studies have demonstrated its ability to inhibit tumor growth and metastasis more effectively than current endocrine therapies. Moreover, clinical trials, such as ELAINE 1 and ELAINE 2, have shown promising outcomes, particularly in combination with CDK4/6 inhibitors, suggesting improved progression-free survival and clinical benefit rates. Lasofoxifene's unique pharmacological profile allows it to stabilize both wild-type and mutant ESR1 receptors, making it a potential targeted therapy for hormone-resistant breast cancer. Despite its potential, several challenges remain, including the risk of drug resistance and the need for further clinical validation. Future research should focus on optimizing combination therapies, understanding resistance mechanisms, and identifying predictive biomarkers to personalize treatment strategies. Lasofoxifene represents a novel therapeutic avenue in the management of ER+ breast cancer, offering hope for patients with limited treatment options due to endocrine therapy resistance.

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