TY - JOUR AU - Alizzi, Z. AU - Roxburgh, P. AU - Cartwright, D. AU - McLaren, A. AU - Park, S. AU - Jones, R. AU - Greening, S. AU - Hudson, E. AU - Green, C. AU - Gray, S. AU - Khalique, S. AU - Karteris, E. AU - Hall, M. TI - Description of a Retrospective Cohort of Epithelial Ovarian Cancer Patients with Brain Metastases: Evaluation of the Role of PARP Inhibitors in this Setting JF - JOURNAL OF CLINICAL MEDICINE J2 - J CLIN MED VL - 12 PY - 2023 IS - 7 SN - 2077-0383 DO - 10.3390/jcm12072497 UR - https://m2.mtmt.hu/api/publication/33939277 ID - 33939277 N1 - Mount Vernon Cancer Centre, Rickmansworth Road, NorthwoodHA6 2RN, United Kingdom Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, G12 0YN, United Kingdom Royal Cornwall Hospitals NHS Trust, Truro, TR1 3LJ, United Kingdom South West Wales Cancer Centre, Swansea, SA2 8QA, United Kingdom Churchill Hospital, Oxford, OX3 7LE, United Kingdom Velindre Cancer Centre, Cardiff, CF14 2TL, United Kingdom University Hospital Southampton, Southampton, SO16 6YD, United Kingdom Lancashire Teaching Hospitals NHS Foundation Trust, Preston, PR2 9HT, United Kingdom College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, United Kingdom Export Date: 1 June 2023 Correspondence Address: Hall, M.; Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, United Kingdom; email: marcia.hall@nhs.net LA - English DB - MTMT ER - TY - JOUR AU - Bansal, Rani AU - Van Swearingen, Amanda E. D. AU - Anders, Carey K. TI - Triple Negative Breast Cancer and Brain Metastases JF - CLINICAL BREAST CANCER J2 - CLIN BREAST CANCER VL - 23 PY - 2023 IS - 8 SP - 825 EP - 831 PG - 7 SN - 1526-8209 DO - 10.1016/j.clbc.2023.07.008 UR - https://m2.mtmt.hu/api/publication/34629748 ID - 34629748 N1 - Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, NC, United States Division of Medical Oncology, Duke Center for Brain and Spine Metastasis, Duke University Medical Center, Durham, NC, United States Export Date: 12 March 2024 CODEN: CBCLB Correspondence Address: Anders, C.K.; Division of Medical Oncology, 10 Searle Center Dr, United States; email: carey.anders@duke.edu LA - English DB - MTMT ER - TY - JOUR AU - Benjamin, M. AU - Malakar, P. AU - Sinha, R.A. AU - Nasser, M.W. AU - Batra, S.K. AU - Siddiqui, J.A. AU - Chakravarti, B. TI - Molecular signaling network and therapeutic developments in breast cancer brain metastasis JF - ADVANCES IN CANCER BIOLOGY-METASTASIS J2 - ADV CANCER BIOL-METASTASIS VL - 7 PY - 2023 SN - 2667-3940 DO - 10.1016/j.adcanc.2022.100079 UR - https://m2.mtmt.hu/api/publication/33688010 ID - 33688010 N1 - Lab Oncology, Dr. B.R.A.I.R.C.H. All India Institute of Medical Sciences, New Delhi, India Department of Biomedical Science and Technology, School of Biological Sciences, Ramakrishna Mission Vivekananda Educational and Research Institute, West Bengal, Narendrapur, 700103, India Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68108, United States Export Date: 12 March 2024 Correspondence Address: Chakravarti, B.; Department of Endocrinology, India; email: vandanaks@gmail.com Correspondence Address: Siddiqui, J.A.; Department of Biochemistry and Molecular Biology, United States; email: jawed.siddiqui@unmc.edu AB - Breast cancer (BC) is one of the most frequently diagnosed cancers in women worldwide. It has surpassed lung cancer as the leading cause of cancer-related death. Breast cancer brain metastasis (BCBM) is becoming a major clinical concern that is commonly associated with ER-ve and HER2+ve subtypes of BC patients. Metastatic lesions in the brain originate when the cancer cells detach from a primary breast tumor and establish metastatic lesions and infiltrate near and distant organs via systemic blood circulation by traversing the BBB. The colonization of BC cells in the brain involves a complex interplay in the tumor microenvironment (TME), metastatic cells, and brain cells like endothelial cells, microglia, and astrocytes. BCBM is a significant cause of morbidity and mortality and presents a challenge to developing successful cancer therapy. In this review, we discuss the molecular mechanism of BCBM and novel therapeutic strategies for patients with brain metastatic BC. © 2022 The Authors LA - English DB - MTMT ER - TY - JOUR AU - El, Gazzar Walaa Bayoumie AU - Albakri, Khaled Anwer AU - Hasan, Hanan AU - Badr, Amira M. AU - Farag, Amina A. AU - Saleh, Othman Mohammad TI - Poly(ADP-ribose) polymerase inhibitors in the treatment landscape of triple-negative breast cancer (TNBC) JF - JOURNAL OF ONCOLOGY PHARMACY PRACTICE J2 - J ONCOL PHAR PRAC VL - 29 PY - 2023 IS - 6 SP - 1467 EP - 1479 PG - 13 SN - 1078-1552 DO - 10.1177/10781552231188903 UR - https://m2.mtmt.hu/api/publication/34229243 ID - 34229243 N1 - Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha City, Egypt Faculty of Medicine, The Hashemite University, Zarqa, Jordan Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Department of Pharmacology and Toxicology, College of Pharmacy, Ain Shams University, Cairo, Egypt Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha City, Egypt Export Date: 3 November 2023 CODEN: JOPPF Correspondence Address: Badr, A.M.; Department of Pharmacology and Toxicology, Saudi Arabia; email: amibadr@ksu.edu.sa AB - Objective: Chemotherapy is the mainstay for triple-negative breast cancer (TNBC) patients. Over the years, the use of chemotherapy for these patients has demonstrated many adversities, including toxicity and resistance, which suggested the need to develop novel alternative therapeutic options, such as poly(ADP-ribose) polymerase inhibitors (PARPi). Herein, we provide an overview on PARPi, mechanisms of action and the role of biomarkers in PARPi sensitivity trials, clinical advances in PARPi therapy for TNBC patients based on the most recent studies and findings of clinical trials, and challenges that prevent PARP inhibitors from achieving high efficacy such as resistance and overlapping toxicities with other chemotherapies.Data sources: Searching for relevant articles was done using PubMed and Cochrane Library databases by using the keywords including TNBC; chemotherapy; PARPi; BRCA; homologous recombination repair (HRR). Studies had to be published in full-text in English in order to be considered.Data summary: Although PARPi have been used in the treatment of local/metastatic breast malignancies that are HER2 nega-tive and has a germline BRCA mutation, several questions are still to be answered in order to maximize the clinical benefit of PARP inhibitors in TNBC treatment, such as questions related to the optimal use in the neoadjuvant and metastatic settings as well as the best combinations with various chemotherapies.Conclusions: PARPi are emerging treatment options for patients with gBRCA1/2 mutations. Determining patients that are most likely to benefit from PARPi and identifying the optimal treatment combinations with high efficacy and fewer side effects are currently ongoing. LA - English DB - MTMT ER - TY - JOUR AU - Ishizuka, Yumiko AU - Horimoto, Yoshiya AU - Eguchi, Hidetaka AU - Murakami, Fumi AU - Nakai, Katsuya AU - Onagi, Hiroko AU - Hayashi, Takuo AU - Ishikawa, Takashi AU - Arai, Masami AU - Watanabe, Junichiro TI - BRCAness of brain lesions reflects a worse outcome for patients with metastatic breast cancer JF - BREAST CANCER RESEARCH AND TREATMENT J2 - BREAST CANCER RES TR VL - 203 PY - 2023 IS - 1 SP - 49 EP - 55 PG - 7 SN - 0167-6806 DO - 10.1007/s10549-023-07115-7 UR - https://m2.mtmt.hu/api/publication/34229240 ID - 34229240 N1 - Funding Agency and Grant Number: Japan Society for the Promotion of Science (JSPS) KAKENHI [21K16388] Funding text: This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number: 21K16388). The authors thank the Laboratory of Molecular and Biochemical Research, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, for technical assistance. We also sincerely appreciate Clear Science Pty Ltd for language editing. AB - PurposeBreast cancer often metastasizes to the central nervous system. Although the prognosis of brain metastases from breast cancer has been considered poor, and systemic therapy has not contributed to an improved prognosis, newer agents are expected to be more effective. BRCAness is defined as the status of homologous recombination deficiency (HRD) in tumor tissue, regardless of the presence of pathogenic germline BRCA1/2 variants. A study employing next-generation sequencing analysis showed that HRD was found relatively frequently in brain metastases of breast cancer patients. However, there have been no studies evaluating BRCAness in brain metastases of breast cancer with more efficient, rapid, and cost-effective methods.MethodsWe retrospectively investigated 17 brain metastases of breast cancer that were surgically resected at our hospital from January 2007 to December 2022. Of these, samples from 15 patients were evaluable for BRCAness by employing multiplex ligation-dependent probe amplification (MLPA) assay.ResultsOf the 15 patients, five patients (33%) had tumors with BRCAness. Clinicopathological factors of patients with brain metastases with BRCAness were not statistically different from those of patients who possessed tumors without BRCAness. Patients with brain metastases with BRCAness had shorter overall survival compared to those without BRCAness (BRCAness, median 15 months (95% CI 2-30) vs. non-BRCAness, median 28.5 months (95% CI 10-60); P = 0.013).ConclusionIn this study, we evaluated BRCAness in brain metastases of breast cancer with the MLPA method, and found that about one-third of patients had BRCAness-positive tumors. The analysis of BRCAness using MLPA has the potential for practical clinical use. LA - English DB - MTMT ER - TY - JOUR AU - Li, Wenbin AU - Gao, Lin AU - Yi, Xin AU - Shi, Shuangfeng AU - Huang, Jie AU - Shi, Leming AU - Zhou, Xiaoyan AU - Wu, Lingying AU - Ying, Jianming TI - Patient Assessment and Therapy Planning Based on Homologous Recombination Repair Deficiency JF - GENOMICS PROTEOMICS & BIOINFORMATICS J2 - GENOM PROTEOM BIOINF VL - 21 PY - 2023 IS - 5 SP - 962 EP - 975 PG - 14 SN - 1672-0229 DO - 10.1016/j.gpb.2023.02.004 UR - https://m2.mtmt.hu/api/publication/34431455 ID - 34431455 N1 - Department of Pathology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Geneplus–Shenzhen, Shenzhen, 518000, China Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China Geneplus–Beijing, Beijing, 102206, China National Institutes for Food and Drug Control, Beijing, 100050, China State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, 200438, China Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China Department of Gynecologic Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Cited By :3 Export Date: 12 March 2024 Correspondence Address: Ying, J.; Department of Pathology, China; email: jmying@cicams.ac.cn LA - English DB - MTMT ER - TY - JOUR AU - Mark, Lasse Ringsted AU - Terp, Simone Karlsson AU - Krarup, Henrik Bygum AU - Thomassen, Mads AU - Pedersen, Inge Sokilde AU - Bogsted, Martin TI - Homologous Recombination Deficiency Detection Algorithms: A Systematic Review JF - CANCERS J2 - CANCERS VL - 15 PY - 2023 IS - 23 PG - 23 SN - 2072-6694 DO - 10.3390/cancers15235633 UR - https://m2.mtmt.hu/api/publication/34629750 ID - 34629750 N1 - Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, DK-9000, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, DK-9000, Denmark Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, DK-9000, Denmark Department of Clinical Genetics, Odense University Hospital, Odense C, DK-5000, Denmark Center for Clinical Data Science, Department of Clinical Medicine, Aalborg University and Research, Education, and Innovation, Aalborg University Hospital, Aalborg, DK-9000, Denmark Export Date: 12 March 2024 Correspondence Address: Mark, L.R.; Department of Molecular Diagnostics, Denmark; email: lasse.mark@rn.dk LA - English DB - MTMT ER - TY - JOUR AU - Ocana-Tienda, Beatriz AU - Perez-Beteta, Julian AU - Jimenez-Sanchez, Juan AU - Molina-Garcia, David AU - Ortiz, de Mendivil Ana AU - Asenjo, Beatriz AU - Albillo, David AU - Perez-Romasanta, Luis A. AU - Valiente, Manuel AU - Zhu, Lucia AU - Garcia-Gomez, Pedro AU - Gonzalez-Del, Portillo Elisabet AU - Llorente, Manuel AU - Carballo, Natalia AU - Arana, Estanislao AU - Perez-Garcia, Victor M. TI - Growth exponents reflect evolutionary processes and treatment response in brain metastases JF - NPJ SYSTEMS BIOLOGY AND APPLICATIONS J2 - NPJ SYST BIOL APPL VL - 9 PY - 2023 IS - 1 PG - 11 SN - 2056-7189 DO - 10.1038/s41540-023-00298-1 UR - https://m2.mtmt.hu/api/publication/34229245 ID - 34229245 N1 - Funding Agency and Grant Number: James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [220020450]; Spanish Ministerio de Ciencia e Innovacion [PID2019-110895RB-I00, PDC2022-133520-I00]; Junta de Comunidades de Castilla-La Mancha [SBPLY/21/180501/000145]; Spanish Ministerio de Ciencia e Innovacion [PRE2020-092178]; University of Castilla-La Mancha [2020-PREDUCLM-15634] Funding text: This research has been supported by the James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (Collaborative award 220020450, https://doi.org/10.37717/220020560), the Spanish Ministerio de Ciencia e Innovacion (grant numbers PID2019-110895RB-I00 and PDC2022-133520-I00), Junta de Comunidades de Castilla-La Mancha (grant SBPLY/21/180501/000145), BOT is supported by the Spanish Ministerio de Ciencia e Innovacion (grant PRE2020-092178) and JJS is supported by the University of Castilla-La Mancha (grant 2020-PREDUCLM-15634). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AB - Tumor growth is the result of the interplay of complex biological processes in huge numbers of individual cells living in changing environments. Effective simple mathematical laws have been shown to describe tumor growth in vitro, or simple animal models with bounded-growth dynamics accurately. However, results for the growth of human cancers in patients are scarce. Our study mined a large dataset of 1133 brain metastases (BMs) with longitudinal imaging follow-up to find growth laws for untreated BMs and recurrent treated BMs. Untreated BMs showed high growth exponents, most likely related to the underlying evolutionary dynamics, with experimental tumors in mice resembling accurately the disease. Recurrent BMs growth exponents were smaller, most probably due to a reduction in tumor heterogeneity after treatment, which may limit the tumor evolutionary capabilities. In silico simulations using a stochastic discrete mesoscopic model with basic evolutionary dynamics led to results in line with the observed data. LA - English DB - MTMT ER - TY - JOUR AU - Su, Zhou AU - Zhang, Li AU - Xue, Shaolong AU - Wang, Youke AU - Ding, Ruining TI - Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis JF - OPEN LIFE SCIENCES J2 - OPEN LIFE SCI VL - 18 PY - 2023 IS - 1 PG - 11 SN - 2391-5412 DO - 10.1515/biol-2022-0559 UR - https://m2.mtmt.hu/api/publication/33923905 ID - 33923905 N1 - Department of Oncology, Sichuan Mianyang 404 Hospital, Sichuan, Mianyang, 621000, China Department of Oncology, West China School of Medicine, SCU, Chengdu, China Department of Oncology, Chengdu University of Traditional Chinese Medicine Affiliated Hospital, Sichuan, Chengdu, China Department of Oncology, Institute of Drug Clinical Trial/GCP Center, Affiliated Hospital of Southwest Medical University, Sichuan, Luzhou, 646000, China Export Date: 1 June 2023 CODEN: OLSPB Correspondence Address: Su, Z.; Department of Oncology, Sichuan, China; email: suzhou1@sina.com AB - Advances in brain imaging have led to a higher incidence of brain metastases (BM) being diagnosed. Stereotactic radiotherapy (SRS), systemic immunotherapy, and targeted drug therapy are commonly used for treating BM. In this study, we summarized the differences in overall survival (OS) between several treatments alone and in combination. We carried out a systematic literature search on Pubmed, EMBASE, and Cochrane Library. Differences in OS associated with Immune checkpoint inhibitors (ICI) alone versus targeted therapy alone and SRS + ICI or ICI alone were evaluated. This analysis was conducted on 11 studies involving 4,154 patients. The comprehensive results of fixed effect model showed that the OS of SRS + ICI group was longer than that of the ICI group (hazard ratio, 1.72; 95% CI: 1.41-2.11; P = 0.22; I (2) = 30%). The combined fixed-effect model showed that the OS time of ICI was longer than that of targeted therapy (hazard ratio, 2.09; 95% CI: 1.37-3.20; P = 0.21; I (2) = 35%). The study had a low risk of bias. In conclusion, our analysis confirmed that immunotherapy alone showed a higher OS benefit in BM patients than targeted therapy alone. The total survival time of patients with SRS combined with ICI was higher than that of patients with single ICI. LA - English DB - MTMT ER - TY - JOUR AU - Tew, Ben Yi AU - Kalfa, Alex J. AU - Yang, Zeyi AU - Hurth, Kyle M. AU - Simon, Thomas AU - Abnoosian, Eric AU - Durant, Stephen T. AU - Hamerlik, Petra AU - Salhia, Bodour TI - ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis JF - CLINICAL CANCER RESEARCH J2 - CLIN CANCER RES VL - 29 PY - 2023 IS - 21 SP - 4492 EP - 4503 PG - 12 SN - 1078-0432 DO - 10.1158/1078-0432.CCR-23-0290 UR - https://m2.mtmt.hu/api/publication/34629747 ID - 34629747 N1 - Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States Early Oncology R&D, AstraZeneca, Cambridge, United Kingdom Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States Cited By :2 Export Date: 12 March 2024 CODEN: CCREF Correspondence Address: Salhia, B.; Department of Translational Genomics, 1450 Biggy St, United States; email: salhia@usc.edu LA - English DB - MTMT ER - TY - JOUR AU - Tomasik, Bartlomiej AU - Bienkowski, Michal AU - Gorska, Zuzanna AU - Gutowska, Klaudia AU - Kumiega, Paulina AU - Jassem, Jacek AU - Duchnowska, Renata TI - Molecular aspects of brain metastases in breast cancer JF - CANCER TREATMENT REVIEWS J2 - CANCER TREAT REV VL - 114 PY - 2023 PG - 13 SN - 0305-7372 DO - 10.1016/j.ctrv.2023.102521 UR - https://m2.mtmt.hu/api/publication/33923906 ID - 33923906 N1 - Department of Oncology and Radiotherapy, Medical University of Gdańsk, 17 Smoluchowskiego St., Gdansk, 80-214, Poland Department of Pathology, Medical University of Gdańsk, 17 Smoluchowskiego St., Gdańsk, 80-214, Poland Department of Oncology, Military Institute of Medicine, 128 Szaserów St., Warsaw, 04-141, Poland Department of Internal Diseases and Endocrinology, Medical University of Warsaw, Warsaw, 02-091, Poland Doctoral School, Medical University of Warsaw, Warsaw, 02-091, Poland Faculty of Medicine, Medical University of Warsaw, Warsaw, 02-091, Poland Export Date: 1 June 2023 CODEN: CTRED Correspondence Address: Jassem, J.; Department of Oncology and Radiotherapy, Smoluchowskiego 17, Poland; email: jjassem@gumed.edu.pl Chemicals/CAS: epidermal growth factor receptor, 79079-06-4; vasculotropin, 127464-60-2; Biomarkers AB - Brain metastases (BM) are a common and devastating manifestation of breast cancer (BC). BM are particularly frequent in the HER2-positive and triple-negative breast cancer phenotypes and usually occur following the metastatic spread to extracranial sites. Several genes mediating BM and biomarkers predicting their risk in BC have been reported in the past decade. These findings have advanced the understanding of BM pathobiology and paved the way for developing new therapeutic strategies but they still warrant a thorough clinical validation. Hence, a better understanding of the mechanistic aspects of BM and delineating the interactions of tumor cells with the brain microenvironment are of utmost importance. This review discusses the molecular basis of the metastatic cascade: the epithelial-mesenchymal transition, cancer, and tumor microenvironment interaction and intravasation, priming of the metastatic niche in the brain, and survival in the new site. We also outline the postulated mechanisms of BC cells' brain tropism. Finally, we discuss advances in the field of biomarkers (both tissue-based and liquid-based) that predict BM from BC. LA - English DB - MTMT ER - TY - JOUR AU - Wilcox, Jessica A. AU - Boire, Adrienne A. TI - Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases JF - CNS DRUGS J2 - CNS DRUGS VL - 37 PY - 2023 IS - 1 SP - 45 EP - 67 PG - 23 SN - 1172-7047 DO - 10.1007/s40263-022-00975-5 UR - https://m2.mtmt.hu/api/publication/33586595 ID - 33586595 N1 - Funding Agency and Grant Number: National Institutes of Health (US) [P30 CA008748, 5R01CA245499] Funding text: The study and its open access publication was funded by National Institutes of Health (US) (Grant nos. P30 CA008748, 5R01CA245499). AB - Leptomeningeal metastases represent an aggressive stage of cancer with few durable treatment options. Improved understanding of cancer biology, neoplastic reliance on oncogenic driver mutations, and complex immune system interactions have resulted in an explosion in cancer-directed therapy in the last two decades to include small molecule inhibitors and immune checkpoint inhibitors. Most of these therapeutics are underexplored in patients with leptomeningeal metastases, limiting extrapolation of extracranial and even intracranial efficacy outcomes to the unique leptomeningeal space. Further confounding our interpretation of drug activity in the leptomeninges is an incomplete understanding of drug penetration through the blood-cerebrospinal fluid barrier of the choroid plexus. Nevertheless, a number of retrospective studies and promising prospective trials provide evidence of leptomeningeal activity of several small molecule and immune checkpoint inhibitors and underscore potential areas of further therapeutic development for patients harboring leptomeningeal disease. LA - English DB - MTMT ER - TY - JOUR AU - Cosgrove, Nicola AU - Vareslija, Damir AU - Keelan, Stephen AU - Elangovan, Ashuvinee AU - Atkinson, Jennifer M. AU - Cocchiglia, Sinead AU - Bane, Fiona T. AU - Singh, Vikrant AU - Furney, Simon AU - Hu, Chunling AU - Carter, Jodi M. AU - Hart, Steven N. AU - Yadav, Siddhartha AU - Goetz, Matthew P. AU - Hill, Arnold D. K. AU - Oesterreich, Steffi AU - Lee, Adrian V AU - Couch, Fergus J. AU - Young, Leonie S. TI - Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 13 PY - 2022 IS - 1 PG - 16 SN - 2041-1723 DO - 10.1038/s41467-022-27987-5 UR - https://m2.mtmt.hu/api/publication/32686131 ID - 32686131 N1 - Funding Agency and Grant Number: Breast Cancer Ireland Programme Grant [18239A01]; Science Foundation Ireland Frontiers AwardScience Foundation Ireland [19/FFP/6443]; Breast Cancer NOW grant [2018JulPR1094]; SFI Strategic Partnership Programme POI [18/SPP/5322]; Breast Cancer NOW Fellowship [2019AugSF1310]; Breast Cancer Research Foundation; National Cancer Institute Outstanding Investigator Award [R35 CA253187]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA225662]; Specialized Program of Research Excellence (SPORE) in breast cancer award [P50 CA116201] Funding text: We are thankful to the patients who generously provided tumor tissue for our studies and to the surgical, pathology, and tissue bank colleagues for their substantial assistance and support. This research was supported in part by the Breast Cancer Ireland Programme Grant, 18239A01 (L.S.Y.), Science Foundation Ireland Frontiers Award, 19/FFP/6443 (L.S.Y., A.D.K.H.) Breast Cancer NOW grant, 2018JulPR1094 (L.S.Y., D.V.), SFI Strategic Partnership Programme POI, 18/SPP/5322 (L.S.Y.), Breast Cancer NOW Fellowship 2019AugSF1310 (D.V.), Breast Cancer Research Foundation; National Cancer Institute Outstanding Investigator Award, R35 CA253187 (F.J.C.); National Cancer Institute grant R01 CA225662 (F.J.C.) and a Specialized Program of Research Excellence (SPORE) in breast cancer award to the Mayo Clinic (P50 CA116201) (F.J.C.). AB - The molecular landscape of breast cancer brain metastases (BCBM) is still understudied, especially for different breast cancer subtypes. Here, the authors characterise subtype-specific BCBMs using genomics and transcriptomics and identify homologous recombination deficiency as a key therapeutic vulnerability. The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis. Importantly, in luminal brain metastases we identify homologous recombination deficiency operative in transcriptomic and genomic data with recurrent breast mutational signatures A, F and K, associated with mismatch repair defects, TP53 mutations and homologous recombination deficiency (HRD) respectively. Utilizing PARP inhibition in patient-derived brain metastatic tumor explants we functionally validate HRD as a key vulnerability. Here, we demonstrate a functionally relevant HRD evident at genomic and transcriptomic levels pointing to genomic instability in breast cancer brain metastasis which is of potential translational significance. LA - English DB - MTMT ER - TY - JOUR AU - Dhakal, Ajay AU - Van Swearingen, Amanda E. D. AU - O’Regan, Ruth AU - Anders, Carey K. TI - Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases JF - CURRENT TREATMENT OPTIONS IN ONCOLOGY J2 - CURR TREAT OPTION ON VL - 23 PY - 2022 IS - 10 SP - 1457 EP - 1476 PG - 20 SN - 1527-2729 DO - 10.1007/s11864-022-01011-w UR - https://m2.mtmt.hu/api/publication/33123863 ID - 33123863 N1 - University of Rochester, Rochester, NY, United States Duke Center for Brain and Spine Metastasis, Duke Cancer Institute, Duke University, Durham, NC, United States Export Date: 2 November 2022 CODEN: CTOOB Correspondence Address: Anders, C.K.; Duke Center for Brain and Spine Metastasis, United States; email: carey.anders@duke.edu LA - English DB - MTMT ER - TY - JOUR AU - Garber, Haven R. AU - Raghavendra, Akshara Singareeka AU - Lehner, Michael AU - Qiao, Wei AU - Gutierrez-Barrera, Angelica M. AU - Tripathy, Debu AU - Arun, Banu AU - Ibrahim, Nuhad K. TI - Incidence and impact of brain metastasis in patients with hereditary BRCA1 or BRCA2 mutated invasive breast cancer JF - NPJ BREAST CANCER J2 - NPJ BREAST CANCER VL - 8 PY - 2022 IS - 1 PG - 8 SN - 2374-4677 DO - 10.1038/s41523-022-00407-z UR - https://m2.mtmt.hu/api/publication/32791587 ID - 32791587 N1 - Funding Agency and Grant Number: Sheila Wynne Research Fund; Nellie B. Connally Research Funds; Cancer Center Support Grant (NCI) [P30 CA016672] Funding text: Presented as Poster at the ASCO, Chicago, 2020. This work was supported by Sheila Wynne Research Fund. The database is supported by the Nellie B. Connally Research Funds and the biostatistical effort was supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672). AB - Patients with hereditary mutations in BRCA1 or BRCA2 (gBRCA1/2) and breast cancer have distinct tumor biology, and encompass a predilection for brain metastasis (BM). We looked into baseline risk of BMs among gBRCA1/2 patients. Patients with gBRCA1/2, stage I-Ill invasive breast cancer seen between 2000-2017 with parenchymal BMs. Among gBRCA1 with distant breast cancer recurrence, 34 of 76 (44.7%) were diagnosed with brain metastases compared to 7 of 42 (16.7%) patients with gBRCA2. In the comparator group, 65 of 182 (35.7%) noncarrier triple-negative breast cancer (TNBC) and a distant recurrence experienced BM's. In a competitive risk analysis using death as a competing factor, the cumulative incidence of BMs was similar between gBRCA1 and noncarrier TNBC patients. The time from primary breast cancer diagnosis to detection of BMs was similar between gBRCA1 and noncarrier TNBC patients {2.4 vs 2.2 years). Survival was poor after BMs (7.8 months for gBRCA1 patients vs. 6.2 months for TNBC noncarriers). Brain was a more common site of initial distant recurrence in gBRCA1 patients versus TNBC noncarriers (26.3% vs. 12.1%). Importantly, the presence of BMs, adversely impacted overall survival across groups (HR 1.68 (95% CI 1.12-2.53), hazard ratio for death if a patient had BMs at the time of initial breast cancer recurrence vs. not). In conclusion, breast cancer BMs is common and is similarly frequent among gBRCA1 and noncarrier patients with recurrent TNBC. Our study highlights the importance of improving the prevention and treatment of BMs in patients with TNBC, gBRCA1 carriers, and noncarriers. LA - English DB - MTMT ER - TY - CHAP AU - Gasparri, M.L. AU - Siconolfi, A. AU - Papadia, A. AU - Di, Micco R. AU - Zuber, V. AU - Gentilini, O.D. AU - Farooqi, A.A. AU - Di, Bartolomeo G. AU - Caserta, D. AU - Bellati, F. AU - Ruscito, I. ED - :Ammad, Ahmad Farooqi ED - Muhammad, Zahid Qureshi ED - Uteuliyev, Yerzhan Sabitaliyevich TI - Brain metastases in breast cancer T2 - Unraveling the Complexities of Metastasis PB - Elsevier CY - Amsterdam SN - 9780128217894 PY - 2022 SP - 63 EP - 85 PG - 23 DO - 10.1016/B978-0-12-821789-4.24001-0 UR - https://m2.mtmt.hu/api/publication/33202322 ID - 33202322 N1 - Department of Gynecology and Obstetrics, Università della Svizzera Italiana (USI), Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland Breast Surgical Unit, Department of General Surgery, San Raffaele University Hospital, Milan, Italy Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan Miller School of Medicine, University of Miami, Miami, FL, United States Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy Cell Therapy Unit and Laboratory of Tumor Immunology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy Department of Gynecology, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany Export Date: 19 January 2024 LA - English DB - MTMT ER - TY - JOUR AU - Kalita-de, Croft Priyakshi AU - Joshi, Vaibhavi AU - Saunus, Jodi M. AU - Lakhani, Sunil R. TI - Emerging Biomarkers for Diagnosis, Prevention and Treatment of Brain Metastases-From Biology to Clinical Utility JF - DISEASES J2 - DISEASES VL - 10 PY - 2022 IS - 1 PG - 14 SN - 2079-9721 DO - 10.3390/diseases10010011 UR - https://m2.mtmt.hu/api/publication/32791588 ID - 32791588 N1 - Funding Agency and Grant Number: Australian National Health and Medical Research CouncilNational Health and Medical Research Council (NHMRC) of Australia [APP1017028] Funding text: This research was funded by a grant from the Australian National Health and Medical Research Council (APP1017028). AB - Primary malignancies of the lung, skin (melanoma), and breast have higher propensity for metastatic spread to the brain. Advances in molecular tumour profiling have aided the development of targeted therapies, stereotactic radiotherapy, and immunotherapy, which have led to some improvement in patient outcomes; however, the overall prognosis remains poor. Continued research to identify new prognostic and predictive biomarkers is necessary to further impact patient outcomes, as this will enable better risk stratification at the point of primary cancer diagnosis, earlier detection of metastatic deposits (for example, through surveillance), and more effective systemic treatments. Brain metastases exhibit considerable inter- and intratumoural heterogeneity-apart from distinct histology, treatment history and other clinical factors, the metastatic brain tumour microenvironment is incredibly variable both in terms of subclonal diversity and cellular composition. This review discusses emerging biomarkers; specifically, the biological context and potential clinical utility of tumour tissue biomarkers, circulating tumour cells, extracellular vesicles, and circulating tumour DNA. LA - English DB - MTMT ER - TY - JOUR AU - Limon, Dror AU - Shachar, Eliya AU - Wolf, Ido AU - Adar, Lyri AU - Hasson, Shira Peleg AU - Ferro, Leora AU - Safra, Tamar TI - Brain metastases in patients with ovarian cancer JF - ACTA ONCOLOGICA J2 - ACTA ONCOL VL - 61 PY - 2022 IS - 6 SP - 757 EP - 763 PG - 7 SN - 0284-186X DO - 10.1080/0284186X.2022.2066985 UR - https://m2.mtmt.hu/api/publication/32831079 ID - 32831079 N1 - Oncology Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Cited By :3 Export Date: 3 November 2023 CODEN: ACTOE Correspondence Address: Safra, T.; Oncology Department, 6 Weizmann Street, Israel; email: prof.tamarsafra@gmail.com Chemicals/CAS: bevacizumab, 216974-75-3, 1438851-35-4; Poly(ADP-ribose) Polymerase Inhibitors AB - Background Brain metastasis (BM) are uncommon among women with epithelial ovarian cancer (EOC). The frequency, risk factors and clinical repercussions of BM in these patients are not well described. Methods We retrospectively evaluated EOC patients treated at our center from 2002 to 2020 and assessed their clinical parameters, risk for BM development and association with overall survival (OS). This cohort has a known high frequency of BRCA mutation carriers (BRCAm) due to women of Ashkenazi Jewish descent. Results Among 1035 EOC patients, 29 (2.8%) were diagnosed with BM. The prevalence of BRCA mutations was more common among women with BM (56.5% vs. 34.3%, p = 0.033). The BM rate in patients with BRCAm was higher than the BM rate in those with wildtype BRCA (BRCAw; 5.1% vs. 2.1%, OR = 2.6; 95% CI: 1.2-5.4, p = 0.013). Median time from diagnosis to BM and from disease recurrence to BM was longer among patients with BRCAm. Median OS was not significantly different among patients with BM versus those without BM (59.4 vs. 73.4 months, p = 0.243). After BM diagnosis, median OS was not statistically significantly different between patients with BRCAm and those with BRCAw (20.6 vs. 12.3 months, p = 0.441). Treatment with poly (ADP-ribose) polymerase inhibitors and bevacizumab had no impact on subsequent development of BM. Conclusions BM are rare among EOC patients. However, the risk is three-fold higher among patients with BRCAm. BM do not significantly alter OS among EOC patients. The higher rate of BM in patients with BRCAm may be related to longer OS in this subpopulation. LA - English DB - MTMT ER - TY - JOUR AU - Rodriguez-Calero, Antonio AU - Gallon, John AU - Akhoundova, Dilara AU - Maletti, Sina AU - Ferguson, Alison AU - Cyrta, Joanna AU - Amstutz, Ursula AU - Garofoli, Andrea AU - Paradiso, Viola AU - Tomlins, Scott A. AU - Hewer, Ekkehard AU - Genitsch, Vera AU - Fleischmann, Achim AU - Vassella, Erik AU - Rushing, Elisabeth J. AU - Grobholz, Rainer AU - Fischer, Ingeborg AU - Jochum, Wolfram AU - Cathomas, Gieri AU - Osunkoya, Adeboye O. AU - Bubendorf, Lukas AU - Moch, Holger AU - Thalmann, George AU - Ng, Charlotte K. Y. AU - Gillessen, Silke AU - Piscuoglio, Salvatore AU - Rubin, Mark A. TI - Alterations in homologous recombination repair genes in prostate cancer brain metastases JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 13 PY - 2022 IS - 1 PG - 10 SN - 2041-1723 DO - 10.1038/s41467-022-30003-5 UR - https://m2.mtmt.hu/api/publication/32831078 ID - 32831078 N1 - Department for BioMedical Research, University of Bern, Bern, Switzerland Institute of Pathology, University of Bern, Bern, Switzerland Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland Department of Oncology, Ludwig Cancer Centre, University of Lausanne, Lausanne, Switzerland Department of Pathology, Institut Curie, University Paris Sciences et Lettres, Paris, France Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland Departments of Pathology and Urology, University of Michigan Medical School, Ann Arbor, MI, United States Institute of Pathology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland Institute of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland Departments of Pathology and Laboratory Medicine, and Urology, Emory University School of Medicine, Atlanta, United States Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland Faculty of Biomedical Sciences, USI, Lugano, Switzerland Department of Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom Bern Center for Precision Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland Cited By :7 Export Date: 7 July 2023 Correspondence Address: Rubin, M.A.; Department for BioMedical Research, Switzerland; email: mark.rubin@dbmr.unibe.ch Correspondence Address: Piscuoglio, S.; Visceral Surgery and Precision Medicine Research Laboratory, Switzerland; email: s.piscuoglio@unibas.ch AB - Improved survival rates for prostate cancer through more effective therapies have also led to an increase in the diagnosis of metastases to infrequent locations such as the brain. Here we investigate the repertoire of somatic genetic alterations present in brain metastases from 51 patients with prostate cancer brain metastases (PCBM). We highlight the clonal evolution occurring in PCBM and demonstrate an increased mutational burden, concomitant with an enrichment of the homologous recombination deficiency mutational signature in PCBM compared to non-brain metastases. Focusing on known pathogenic alterations within homologous recombination repair genes, we find 10 patients (19.6%) fulfilling the inclusion criteria used in the PROfound clinical trial, which assessed the efficacy of PARP inhibitors (PARPi) in homologous recombination deficient prostate cancer. Eight (15.7%) patients show biallelic loss of one of the 15 genes included in the trial, while 5 patients (9.8%) harbor pathogenic alterations in BRCA1/2 specifically. Uncovering these molecular features of PCBM may have therapeutic implications, suggesting the need of clinical trial enrollment of PCBM patients when evaluating potential benefit from PARPi. The diagnosis of prostate cancer brain metastasis (PCBM) has increased. Here, the authors investigate the landscape of somatic genetic alterations in brain metastases in a PCBM cohort of 51 patients with non-synchronous matched primary samples available for 20 patients. LA - English DB - MTMT ER - TY - JOUR AU - Ruscitto, Federica AU - Roda, Niccolo AU - Priami, Chiara AU - Migliaccio, Enrica AU - Pelicci, Pier Giuseppe TI - Beyond Genetics: Metastasis as an Adaptive Response in Breast Cancer JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 11 PG - 22 SN - 1661-6596 DO - 10.3390/ijms23116271 UR - https://m2.mtmt.hu/api/publication/33031104 ID - 33031104 N1 - Funding Agency and Grant Number: AIRC (Associazione Italiana per la Ricerca sul Cancro) [AIRC-IG-2017-20162]; MIUR (Italian Ministry of University and Research) [PRIN 2017L8FWY8]; Fondazione IEO-CCM fellowship Funding text: AIRC (Associazione Italiana per la Ricerca sul Cancro): AIRC-IG-2017-20162. MIUR (Italian Ministry of University and Research): PRIN 2017L8FWY8. N.R was recipient of Fondazione IEO-CCM fellowship. AB - Metastatic disease represents the primary cause of breast cancer (BC) mortality, yet it is still one of the most enigmatic processes in the biology of this tumor. Metastatic progression includes distinct phases: invasion, intravasation, hematogenous dissemination, extravasation and seeding at distant sites, micro-metastasis formation and metastatic outgrowth. Whole-genome sequencing analyses of primary BC and metastases revealed that BC metastatization is a non-genetically selected trait, rather the result of transcriptional and metabolic adaptation to the unfavorable microenvironmental conditions which cancer cells are exposed to (e.g., hypoxia, low nutrients, endoplasmic reticulum stress and chemotherapy administration). In this regard, the latest multi-omics analyses unveiled intra-tumor phenotypic heterogeneity, which determines the polyclonal nature of breast tumors and constitutes a challenge for clinicians, correlating with patient poor prognosis. The present work reviews BC classification and epidemiology, focusing on the impact of metastatic disease on patient prognosis and survival, while describing general principles and current in vitro/in vivo models of the BC metastatic cascade. The authors address here both genetic and phenotypic intrinsic heterogeneity of breast tumors, reporting the latest studies that support the role of the latter in metastatic spreading. Finally, the review illustrates the mechanisms underlying adaptive stress responses during BC metastatic progression. LA - English DB - MTMT ER - TY - JOUR AU - Simsek, M. AU - Aliyev, A. AU - Baydas, T. AU - Besiroglu, M. AU - Demir, T. AU - Shbair, A.T.M. AU - Seker, M. AU - Turk, H.M. TI - Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study JF - BREAST JOURNAL J2 - BREAST J VL - 2022 PY - 2022 SN - 1075-122X DO - 10.1155/2022/5763810 UR - https://m2.mtmt.hu/api/publication/33202323 ID - 33202323 N1 - BezmialemVakif University, Faculty of Medicine, Department of Medical Oncology, Fatih, Istanbul, Turkey BezmialemVakif University, Faculty of Medicine, Department of Internal Medicine, Fatih, Istanbul, Turkey Export Date: 2 November 2022 CODEN: BRJOF Correspondence Address: Simsek, M.; BezmialemVakif University, Fatih, Turkey; email: mdmelih@gmail.com LA - English DB - MTMT ER - TY - JOUR AU - Wang, Ziqiong AU - Chen, Bo AU - Chen, Jiyang AU - Wu, Zhixuan AU - Gu, Hongyi AU - Wang, Ying AU - Dai, Xuanxuan TI - A Novel Nomogram Model to Identify Candidates and Predict the Possibility of Benefit From Primary Tumor Resection Among Female Patients With Metastatic Infiltrating Duct Carcinoma of the Breast: A Large Cohort Study JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 12 PY - 2022 PG - 14 SN - 2234-943X DO - 10.3389/fonc.2022.798016 UR - https://m2.mtmt.hu/api/publication/32791590 ID - 32791590 N1 - Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China The First Clinical College, Wenzhou Medical University, Wenzhou, China Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China Export Date: 7 February 2023 Correspondence Address: Dai, X.; Department of Thyroid and Breast Surgery, China; email: daoshidaixuanxuan@126.com AB - BackgroundThe impact of primary site surgery on survival remains controversial in female patients with stage IV breast cancer. The purpose of this study was to investigate the role of primary tumor surgery in patients with stage IV breast cancer and concurrently develop a nomogram to identify which patients will benefit from surgery. MethodsWe retrospectively searched the SEER database for female patients newly diagnosed with stage IV breast infiltrating duct carcinoma (BIDC) between 2010 and 2015 and then divided them into surgery and non-surgery groups. The propensity score matching (PSM) method was implemented to eliminate the bias, and Kaplan-Meier survival analysis was generated to compare the overall survival (OS) and cancer-specific survival (CSS) between the two groups. After PSM, Cox regression analyses were performed to determine the independent protective value of primary tumor surgery, while logistic regression analyses were utilized to uncover significant predictors of surgical benefit and establish a screening nomogram for female patients with stage IV BIDC. Nomogram performance was evaluated by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Result5,475 patients with stage IV BIDC were included in this study, and 2,375 patients (43.38%) received primary tumor surgery. After PSM, the median CSS was 53 months (95% CI: 46.84-59.16) in the surgery group compared with only 33 months (95% CI: 30.05-35.95) in the non-surgery group. We further found that primary tumor surgery was an independent protective factor for patients with stage IV BIDC. The independent factors affecting the benefit of locoregional surgery in patients with stage IV BIDC included histological grade, T stage, molecular subtype, lung metastasis, liver metastasis, brain metastasis, and marital status. The AUC of the nomogram was 0.785 in the training set and 0.761 in the testing set. The calibration curves and DCA confirmed that the nomogram could precisely predict the possibility of benefit from primary tumor resection. ConclusionOur study suggested that primary tumor surgery improved the prognosis of female patients with stage IV BIDC and developed a nomogram to quantify the probability of surgical benefit to help identify surgical candidates clinically. LA - English DB - MTMT ER - TY - JOUR AU - Bertucci, Francois AU - Goncalves, Anthony AU - Guille, Arnaud AU - Adelaide, Jose AU - Garnier, Severine AU - Carbuccia, Nadine AU - Billon, Emilien AU - Finetti, Pascal AU - Sfumato, Patrick AU - Monneur, Audrey AU - Pecheux, Christophe AU - Khran, Martin AU - Brunelle, Serge AU - Mescam, Lenaig AU - Thomassin-Piana, Jeanne AU - Poizat, Flora AU - Charafe-Jauffret, Emmanuelle AU - Turrini, Olivier AU - Lambaudie, Eric AU - Provansal, Magali AU - Extra, Jean-Marc AU - Madroszyk, Anne AU - Gilabert, Marine AU - Sabatier, Renaud AU - Vicier, Cecile AU - Mamessier, Emilie AU - Chabannon, Christian AU - Pakradouni, Jihane AU - Viens, Patrice AU - Andre, Fabrice AU - Gravis, Gwenaelle AU - Popovici, Cornel AU - Birnbaum, Daniel AU - Chaffanet, Max TI - Prospective high-throughput genome profiling of advanced cancers: results of the PERMED-01 clinical trial JF - GENOME MEDICINE J2 - GENOME MED VL - 13 PY - 2021 IS - 1 PG - 20 SN - 1756-994X DO - 10.1186/s13073-021-00897-9 UR - https://m2.mtmt.hu/api/publication/32294895 ID - 32294895 N1 - Funding Agency and Grant Number: SIRIC; Ruban Rose; Association La Marie-Do; Fondation Groupe EDF; Centre d'Investigations Cliniques [CICp1409]; label Ligue EL2016; label Ligue EL2019 Funding text: This work was supported by SIRIC (PV), label Ligue EL2016 (DB) and EL2019 (FB), Ruban Rose (DB), Association La Marie-Do (FB), Fondation Groupe EDF (DB), and Centre d'Investigations Cliniques (CICp1409). AB - Background: The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome arraycomparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores.Methods: Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 "candidate cancer" genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a "matched therapy" and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES).Results: Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68-75%). Only 94/550 patients (17%, 95%CI 14-21) received an "AGA-matched therapy" on progression. The most frequent AGAs leading to "matched therapy" included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such "matched therapy" improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of "matched therapy" was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with "matched therapy," and 6-month overall survival (OS) was 62% (95%CI 52-73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/ aCGH.Conclusions: Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a "matched therapy" in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results. LA - English DB - MTMT ER - TY - JOUR AU - Bryan, Sarah AU - Witzel, Isabell AU - Borgmann, Kerstin AU - Oliveira-Ferrer, Leticia TI - Molecular Mechanisms Associated with Brain Metastases in HER2-Positive and Triple Negative Breast Cancers JF - CANCERS J2 - CANCERS VL - 13 PY - 2021 IS - 16 PG - 19 SN - 2072-6694 DO - 10.3390/cancers13164137 UR - https://m2.mtmt.hu/api/publication/32344728 ID - 32344728 N1 - Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany Center of Oncology, Laboratory of Radiobiology & Experimental Radiooncology, Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, 20251, Germany Export Date: 2 November 2021 Correspondence Address: Oliveira-Ferrer, L.; Department of Gynaecology, Germany; email: ferrer@uke.de AB - Simple Summary Breast cancer, the most common malignant tumor among women worldwide, remains an incurable disease once it has spread to the brain. Past research has shown that a primary breast cancer's biology is an important determining factor predisposing its ability to form brain metastases. This review summarizes our current understanding of which genes, mutations, and molecules cause this increased ability to spread to and survive in the brain, specifically focusing on the different stages of this process. This knowledge may help us develop more effective, tumor-specific therapies and, as such, increase the chance of recovery for patients with breast cancer brain metastases. Breast cancer (BC) is the most frequent cause of cancer-associated death for women worldwide, with deaths commonly resulting from metastatic spread to distant organs. Approximately 30% of metastatic BC patients develop brain metastases (BM), a currently incurable diagnosis. The influence of BC molecular subtype and gene expression on breast cancer brain metastasis (BCBM) development and patient prognosis is undeniable and is, therefore, an important focus point in the attempt to combat the disease. The HER2-positive and triple-negative molecular subtypes are associated with an increased risk of developing BCBM. Several genetic and molecular mechanisms linked to HER2-positive and triple-negative BC breast cancers appear to influence BCBM formation on several levels, including increased development of circulating tumor cells (CTCs), enhanced epithelial-mesenchymal transition (EMT), and migration of primary BC cells to the brain and/or through superior local invasiveness aided by cancer stem-like cells (CSCs). These specific BC characteristics, together with the ensuing developments at a clinical level, are presented in this review article, drawing a connection between research findings and related therapeutic strategies aimed at preventing BCBM formation and/or progression. Furthermore, we briefly address the critical limitations in our current understanding of this complex topic, highlighting potential focal points for future research. LA - English DB - MTMT ER - TY - JOUR AU - Diossy, Miklos AU - Sztupinszki, Zsófia AU - Borcsok, Judit AU - Krzystanek, Marcin AU - Tisza, Viktoria AU - Spisák, Sándor AU - Rusz, Orsolya AU - Tímár, József AU - Csabai, István AU - Fillinger, János AU - Moldvay, Judit AU - Pedersen, Anders Gorm AU - Szüts, Dávid AU - Szállási, Zoltán TI - A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures JF - NPJ PRECISION ONCOLOGY J2 - NPJ PRECIS ONCOL VL - 5 PY - 2021 IS - 1 PG - 8 SN - 2397-768X DO - 10.1038/s41698-021-00199-8 UR - https://m2.mtmt.hu/api/publication/32076418 ID - 32076418 N1 - Funding Agency and Grant Number: Research and Technology Innovation Fund [KTIA_NAP_13-2014-0021]; Breast Cancer Research Foundation [BCRF-17-156]; Kraeftens Bekaempelse [R281-A16566]; Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant [NNF15OC0016584]; Department of Defense through the Prostate Cancer Research ProgramUnited States Department of Defense [W81XWH-18-2-0056]; Det Frie Forskningsrad Sundhed og Sygdom [7016-00345B]; Velux FoundationVelux Fonden [00018310] Funding text: The results shown here are based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.This work was supported by the Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 to Z.Szallasi.), Breast Cancer Research Foundation (BCRF-17-156 to Z.Szallasi.), Kraeftens Bekaempelse (R281-A16566 to Z.Szallasi.), the Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant (NNF15OC0016584 to Z.Szallasi. and I.C.), Department of Defense through the Prostate Cancer Research Program (W81XWH-18-2-0056 to Z.Szallasi.), Det Frie Forskningsrad Sundhed og Sygdom (7016-00345B to Z.Szallasi.), and the Velux Foundation (00018310 to Z.Sztupinszki. and J.B.). LA - English DB - MTMT ER - TY - JOUR AU - Gallego, Alejandro AU - Garrido, Diego AU - Yebenes, Laura AU - Mendiola, Marta AU - Castelo, Beatriz AU - Redondo, Andres TI - Long-term response to olaparib in BRCA1-related ovarian cancer with brain metastases JF - INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER J2 - INT J GYNECOL CANCER VL - 31 PY - 2021 IS - 9 SP - 1292 EP - 1296 PG - 5 SN - 1048-891X DO - 10.1136/ijgc-2020-002225 UR - https://m2.mtmt.hu/api/publication/32343828 ID - 32343828 N1 - Department of Medical Oncology, Hospital Universitario la Paz, Madrid, Spain Department of Radiology, Hospital Universitario la Paz, Madrid, Spain Department of Pathology, Hospital Universitario la Paz, Madrid, Spain Translational Oncology Laboratory, IdiPAZ, Hospital Universitario la Paz, Madrid, Spain Export Date: 7 February 2023 CODEN: IJGCE LA - English DB - MTMT ER - TY - JOUR AU - Jiang, Tao AU - Yan, Yan AU - Zhou, Kun AU - Su, Chunxia AU - Ren, Shengxiang AU - Li, Nan AU - Hou, Likun AU - Guo, Xianchao AU - Zhu, Wei AU - Zhang, Henghui AU - Lin, Jie AU - Zhang, Jun AU - Zhou, Caicun TI - Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma JF - NPJ PRECISION ONCOLOGY J2 - NPJ PRECIS ONCOL VL - 5 PY - 2021 IS - 1 PG - 9 SN - 2397-768X DO - 10.1038/s41698-021-00151-w UR - https://m2.mtmt.hu/api/publication/32062157 ID - 32062157 N1 - Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871865, 81874036, 81972167]; Shanghai Education Development Foundation [16SG18]; Shanghai Municipal Education CommissionShanghai Municipal Education Commission (SHMEC) [16SG18]; Backbone Program of Shanghai Pulmonary Hospital [FKGG1802]; Shanghai Pujiang Talent Plan [2019PJD048]; Shanghai Key disciplines of Respiratory [2017ZZ02012]; University of Kansas Medical Center; Shanghai Sailing Program [20YF1407500] Funding text: This study was supported in part by grants from the National Natural Science Foundation of China (No. 81871865, 81874036, and 81972167), "Shuguang Program" supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (No. 16SG18), the Backbone Program of Shanghai Pulmonary Hospital (No. FKGG1802), Shanghai Pujiang Talent Plan (No. 2019PJD048), and Shanghai Key disciplines of Respiratory (No. 2017ZZ02012), the start-up funds from the University of Kansas Medical Center (J.Z.), and the Shanghai Sailing Program (No. 20YF1407500). AB - Characterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD) patients with BM and compared to their paired primary tumors. We observed significantly higher intertumor heterogeneity between paired primary tumors and BMs, with only a median of 8.3% of genetic mutations identified as shared. Phylogenetic analysis revealed that BM-competent clones genetically diverged from their primary tumors at relatively early stage, suggesting that the parallel progression model is dominant. In cases with synchronous lymph node metastasis (LNM), phylogenetic analysis suggested that BM is a later event than LNM. MIF analysis found that BMs exhibited significantly lower CD8(+) T cell infiltration (P=0.048), and elevated CD4(+)Foxp3(+) T cell infiltration (P=0.036) and PD-1 expression (P=0.047) in comparison to the matched primary tumors, indicating an immunosuppressive microenvironment in BMs. The current study revealed the discrepancy of mutational landscape as well as tumor immune microenvironment between BM and its primary tumor - such findings shall help us better understand the unique biological features of BM and develop innovative strategies accordingly for our patients with LUAD. LA - English DB - MTMT ER - TY - JOUR AU - Lam, T.-C. TI - Comprehensive genomic profiling-guided niraparib treatment of triple-negative breast cancer in a patient with extensive brain metastasis: Case report and literature review JF - JOURNAL OF IMMUNOTHERAPY AND PRECISION ONCOLOGY J2 - J IMMUNOTHER PREC ONC VL - 4 PY - 2021 IS - 1 SP - 16 EP - 20 PG - 5 SN - 2666-2345 DO - 10.36401/JIPO-20-24 UR - https://m2.mtmt.hu/api/publication/32474745 ID - 32474745 N1 - Export Date: 2 November 2021 Correspondence Address: Lam, T.-C.; Department of Clinical Oncology, Hong Kong; email: lamtc03@hku.hk LA - English DB - MTMT ER - TY - JOUR AU - Lu, Cheng-Hua AU - Wu, Chia-Hsin AU - Tsai, Mong-Hsun AU - Lai, Liang-Chuan AU - Chuang, Eric Y. TI - MutScape: an analytical toolkit for probing the mutational landscape in cancer genomics JF - NAR GENOMICS AND BIOINFORMATICS J2 - NAR GENOM BIOINF VL - 3 PY - 2021 IS - 4 PG - 10 SN - 2631-9268 DO - 10.1093/nargab/lqab099 UR - https://m2.mtmt.hu/api/publication/32686132 ID - 32686132 N1 - Funding Agency and Grant Number: Industrial Technology Research Institute [110HT654005]; YongLin Healthcare Foundation [FB002-7]; National Taiwan UniversityNational Taiwan University [GTZ300, 109L104704-2] Funding text: Industrial Technology Research Institute [110HT654005]; YongLin Healthcare Foundation [FB002-7]; National Taiwan University [GTZ300; 109L104704-2]. AB - Cancer genomics has been evolving rapidly, fueled by the emergence of numerous studies and public databases through next-generation sequencing technologies. However, the downstream programs used to preprocess and analyze data on somatic mutations are scattered in different tools, most of which require specific input formats. Here, we developed a user-friendly Python toolkit, MutScape, which provides a comprehensive pipeline of filtering, combination, transformation, analysis and visualization for researchers, to easily explore the cohort-based mutational characterization for studying cancer genomics when obtaining somatic mutation data. MutScape not only can preprocess millions of mutation records in a few minutes, but also offers various analyses simultaneously, including driver gene detection, mutational signature, large-scale alteration identification and actionable biomarker annotation. Furthermore, MutScape supports somatic variant data in both variant call format and mutation annotation format, and leverages caller combination strategies to quickly eliminate false positives. With only two simple commands, robust results and publication-quality images are generated automatically. Herein, we demonstrate the ability of MutScape to correctly reproduce known results using breast cancer samples from The Cancer Genome Atlas. More significantly, discovery of novel results in cancer genomic studies is enabled through the advanced features in MutScape. MutScape is freely available on GitHub, at https://github.con danitalu724/MutScape. LA - English DB - MTMT ER - TY - JOUR AU - Morgan, Alexander J. AU - Giannoudis, Athina AU - Palmieri, Carlo TI - The genomic landscape of breast cancer brain metastases: a systematic review JF - LANCET ONCOLOGY J2 - LANCET ONCOL VL - 22 PY - 2021 IS - 1 SP - E7 EP - E17 PG - 11 SN - 1470-2045 DO - 10.1016/S1470-2045(20)30556-8 UR - https://m2.mtmt.hu/api/publication/32062158 ID - 32062158 N1 - Funding Agency and Grant Number: Liverpool Experimental Cancer Medicine Centre (Liverpool, UK) [C18616/A25153]; Cancer Research UK (London, UK)Cancer Research UK; Clatterbridge Cancer Centre (Liverpool, UK); North West Cancer Research (Liverpool, UK); Clatterbridge Cancer Charity (Liverpool, UK) Funding text: We thank the Liverpool Experimental Cancer Medicine Centre (Liverpool, UK) for providing infrastructure support for this research (grant reference C18616/A25153), and Cancer Research UK (London, UK), Clatterbridge Cancer Centre (Liverpool, UK), North West Cancer Research (Liverpool, UK), and Clatterbridge Cancer Charity (Liverpool, UK) for research support. AB - Breast cancer brain metastases are an increasing clinical problem. Studies have shown that brain metastases from breast cancer have a distinct genomic landscape to that of the primary tumour, including the presence of mutations that are absent in the primary breast tumour. In this Review, we aim to review and evaluate genomic sequencing data for breast cancer brain metastases by searching PubMed, Embase, and Scopus for relevant articles published in English between database inception and May 30, 2020. Extracted information includes data for mutations, receptor status (eg, immunohistochemistry and Prediction Analysis of Microarray 50 [PAM50]), and copy number alterations from published manuscripts and supplementary materials. Of the 431 articles returned by the database search, 13 (3%) breast cancer brain metastases sequencing studies, comprising 164 patients with sequenced brain metastases, met all our inclusion criteria. We identified 268 mutated genes that were present in two or more breast cancer brain metastases samples. Of these 268 genes, 22 (8%) were mutated in five or more patients and pathway enrichment analysis showed their involvement in breast cancer-related signalling pathways, regulation of gene transcription, cell cycle, and DNA repair. Actionability analysis using the Drug Gene Interaction Database revealed that 15 (68%) of these 22 genes are actionable drug targets. In addition, immunohistochemistry and PAM50 data showed receptor discordancy between primary breast cancers and their paired brain metastases. This systematic review provides a detailed overview of the most commonly mutated genes identified in samples of breast cancer brain metastases and their clinical relevance. These data highlight the differences between primary breast cancers and brain metastases and the importance of acquiring and analysing brain metastasis samples for further study. LA - English DB - MTMT ER - TY - JOUR AU - Papp, Orsolya AU - Doma, Viktória AU - Gil, J. AU - Markó-Varga, G. AU - Kárpáti, Sarolta AU - Tímár, József AU - Vízkeleti, Laura TI - Organ specific copy number variations in visceral metastases of human melanoma JF - CANCERS J2 - CANCERS VL - 13 PY - 2021 IS - 23 PG - 18 SN - 2072-6694 DO - 10.3390/cancers13235984 UR - https://m2.mtmt.hu/api/publication/32529350 ID - 32529350 N1 - Funding Agency and Grant Number: Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K135540]; Research and Technology Innovation Fund [KTIA_NAP_13-2-2014-0021, NAP_B13-2014, 2017-1.2.1.NKP-0002]; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [NVKP-16-1-2016-004] Funding text: This work was supported by the Hungarian Scientific Research Fund-OTKA K135540 and the Research and Technology Innovation Fund (KTIA_NAP_13-2-2014-0021, NAP_B13-2014and 2017-1.2.1.NKP-0002 programs). Project no. NVKP-16-1-2016-004 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the NVKP_16 funding scheme. LA - English DB - MTMT ER - TY - JOUR AU - Rattray, Zahra AU - Deng, Gang AU - Zhang, Shenqi AU - Shirali, Anupama AU - May, Christopher K. AU - Chen, Xiaoyong AU - Cuffari, Benedette J. AU - Liu, Jun AU - Zou, Pan AU - Rattray, Nicholas J. W. AU - Johnson, Caroline H. AU - Dubljevic, Valentina AU - Campbell, James A. AU - Huttner, Anita AU - Baehring, Joachim M. AU - Zhou, Jiangbing AU - Hansen, James E. TI - ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody JF - JCI INSIGHT J2 - JCI INSIGHT VL - 6 PY - 2021 IS - 14 PG - 14 SN - 2379-3708 DO - 10.1172/jci.insight.145875 UR - https://m2.mtmt.hu/api/publication/32344729 ID - 32344729 N1 - Funding Agency and Grant Number: National Institute of Neurological Diseases and Stroke of the NIH [R01NS112223]; Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program [W81XWH-19-1-0649]; Yale Department of Therapeutic Radiology; Lion Heart Fund Pilot Grant; Patrys Ltd.; Yale Craig fund; Yale Kalimeris fund Funding text: Research reported in this publication was supported by the National Institute of Neurological Diseases and Stroke of the NIH under award no. R01NS112223 (JEH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program under award no. W81XWH-19-1-0649 (JEH). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick Maryland, USA, is the awarding and administering acquisition office. In conducting research using animals, the investigators adhered to the laws of the United States and regulations of the Department of Agriculture. This work was also supported in part by the Yale Department of Therapeutic Radiology and Yale Kalimeris and Craig funds (JEH), a Lion Heart Fund Pilot Grant (JEH), and a Patrys Ltd.-sponsored research agreement (JEH). The authors gratefully acknowledge Mark Saba of the Yale University Information Technology Services for assistance in preparation of the graphical abstract. AB - The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus. LA - English DB - MTMT ER - TY - JOUR AU - Sammons, S. AU - Van, Swearingen A.E.D. AU - Chung, C. AU - Anders, C.K. TI - Advances in the management of breast cancer brain metastases JF - NEURO-ONCOLOGY ADVANCES J2 - NEUROONCOL ADV VL - 3 PY - 2021 SP - V63 EP - V74 SN - 2632-2498 DO - 10.1093/noajnl/vdab119 UR - https://m2.mtmt.hu/api/publication/33939299 ID - 33939299 N1 - Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Durham, NC, United States Duke Center for Brain and Spine Metastasis, Duke Cancer Institute, Durham, NC, United States Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States Cited By :5 Export Date: 1 June 2023 Correspondence Address: Sammons, S.; Multidisciplinary Breast Program, 10 Bryan Searle Drive, Seeley G. Mudd Bldg., United States; email: sarah.sammons@duke.edu LA - English DB - MTMT ER - TY - JOUR AU - Sztupinszki, Zsófia AU - Diossy, Miklos AU - Borcsok, Judit AU - Prosz, Aurel AU - Cornelius, Nanna AU - Kjeldsen, Maj K. AU - Mirza, Mansoor R. AU - Szállási, Zoltán TI - Comparative Assessment of Diagnostic Homologous Recombination Deficiency-Associated Mutational Signatures in Ovarian Cancer JF - CLINICAL CANCER RESEARCH J2 - CLIN CANCER RES VL - 27 PY - 2021 IS - 20 SP - 5681 EP - 5687 PG - 7 SN - 1078-0432 DO - 10.1158/1078-0432.CCR-21-0981 UR - https://m2.mtmt.hu/api/publication/32474433 ID - 32474433 N1 - Funding Agency and Grant Number: Research and Technology Innovation Fund [KTIA_NAP_13-2014-0021, 2017-1.2.1-NKP-2017-00002]; Breast Cancer Research Foundation [BCRF-20-159]; Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant [NNF15OC0016584]; Kraeftens Bekaempelses Videnskabelige Udvalg [R281A16566]; Det Frie Forskningsra~ d, Sundhed og Sygdom [7016-00345B]; Department of Defense through the Prostate Cancer Research ProgramUnited States Department of Defense [W81XWH-18-2-0056]; Basser Foundation; Velux Foundation [00018310] Funding text: This work was supported by the Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 and 2017-1.2.1-NKP-2017-00002, to Z. Szallasi), Breast Cancer Research Foundation (BCRF-20-159, to Z. Szallasi), the Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant (NNF15OC0016584, to Z. Szallasi), Kraeftens Bekaempelses Videnskabelige Udvalg (award number R281A16566, to Z. Szallasi), Det Frie Forskningsra~ d, Sundhed og Sygdom (award number, 7016-00345B, to Z. Szallasi), Department of Defense through the Prostate Cancer Research Program (award number W81XWH-18-2-0056, to Z. Szallasi), and Basser Foundation (to Z. Szallasi). Z. Sztupinszki and J. Borcsok were supported by Velux Foundation 00018310 grant. The results shown here are based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/and the International Cancer Genome Consortium (ICGC): https://icgc.org/. AB - Purpose: Homologous recombination (HR) deficiency (HRD) is one of the key determinants of PARP inhibitor response in ovarian cancer, and its accurate detection in tumor biopsies is expected to improve the efficacy of this therapy. Because HRD induces a wide array of genomic aberrations, mutational signatures may serve as a companion diagnostic to identify PARP inhibitor-responsive cases. Experimental Design: From the The Cancer Genome Atlas (TCGA) whole-exome sequencing (WES) data, we extracted different types of mutational signature-based HRD measures, such as the HRD score, genome-wide LOH, and HRDetect trained on ovarian and breast cancer-specific sequencing data. We compared their performance to identify BRCA1/2-deficient cases in the TCGA ovarian cancer cohort and predict survival benefit in platinum-treated, BRCA1/2 wild-type ovarian cancer. Results: We found that the HRD score, which is based on large chromosomal alterations alone, performed similarly well to an ovarian cancer-specific HRDetect, which incorporates mutations on a finer scale as well (AUC = 0.823 vs. AUC = 0.837). In an independent cohort these two methods were equally accurate predicting long- term survival after platinum treatment (AUC = 0.787 vs. AUC = 0.823). We also found that HRDetect trained on ovarian cancer was more accurate than HRDetect trained on breast cancer data (AUC = 0.837 vs. AUC = 0.795; P = 0.0072). Conclusions: When WES data are available, methods that quantify only large chromosomal alterations such as the HRD score and HRDetect that captures a wider array of HRD-induced genomic aberrations are equally efficient identifying HRD ovarian cancer cases. LA - English DB - MTMT ER - TY - JOUR AU - Wang, Yajie AU - Ye, Fangzhou AU - Liang, Yiran AU - Yang, Qifeng TI - Breast cancer brain metastasis: insight into molecular mechanisms and therapeutic strategies JF - BRITISH JOURNAL OF CANCER J2 - BRIT J CANCER VL - 125 PY - 2021 IS - 8 SP - 1056 EP - 1067 PG - 12 SN - 0007-0920 DO - 10.1038/s41416-021-01424-8 UR - https://m2.mtmt.hu/api/publication/32344730 ID - 32344730 AB - Breast cancer is one of the most prevalent malignancies in women worldwide. Early-stage breast cancer is considered a curable disease; however, once distant metastasis occurs, the 5-year overall survival rate of patients becomes significantly reduced. There are four distinct metastatic patterns in breast cancer: bone, lung, liver and brain. Among these, breast cancer brain metastasis (BCBM) is the leading cause of death; it is highly associated with impaired quality of life and poor prognosis due to the limited permeability of the blood-brain barrier and consequent lack of effective treatments. Although the sequence of events in BCBM is universally accepted, the underlying mechanisms have not yet been fully elucidated. In this review, we outline progress surrounding the molecular mechanisms involved in BCBM as well as experimental methods and research models to better understand the process. We further discuss the challenges in the management of brain metastases, as well as providing an overview of current therapies and highlighting innovative research towards developing novel efficacious targeted therapies. LA - English DB - MTMT ER - TY - JOUR AU - Wu, Chia-Hsin AU - Yeh, Hsien-Tang AU - Hsieh, Chia-Shan AU - Huang, Chi-Cheng AU - Chattopadhyay, Amrita AU - Chung, Yuan-Chiang AU - Tu, Shih-Hsin AU - Li, Yung-Hua AU - Lu, Tzu-Pin AU - Lai, Liang-Chuan AU - Hou, Ming-Feng AU - Chang, King-Jen AU - Tsai, Mong-Hsun AU - Chuang, Eric Y. TI - Evolutionary Trajectories and Genomic Divergence in Localized Breast Cancers after Ipsilateral Breast Tumor Recurrence JF - CANCERS J2 - CANCERS VL - 13 PY - 2021 IS - 8 PG - 20 SN - 2072-6694 DO - 10.3390/cancers13081821 UR - https://m2.mtmt.hu/api/publication/32013902 ID - 32013902 N1 - Funding Agency and Grant Number: Center of Biotechnology, National Taiwan University, Taiwan [GTZ300] Funding text: This work was supported by the Center of Biotechnology, National Taiwan University, Taiwan (grant number GTZ300). Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 10617, Taiwan Department of Surgery, Lotung Poh-Ai Hospital, Yilan County, 26546, Taiwan Genome and Systems Biology Degree Program, National Taiwan University, Taipei, 10617, Taiwan Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan Bioinformatics and Biostatistics Core, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, 10055, Taiwan Department of Breast Surgery, Dajia Branch, Kuang Tien General Hospital, Taichung, 43761, Taiwan Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan Department of Public Health, National Taiwan University, Taipei, 10055, Taiwan Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan Department of Surgery, National Taiwan University Hospital, Taipei, 10016, Taiwan Institute of Biotechnology, National Taiwan University, Taipei, 10672, Taiwan Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 31057, Taiwan Export Date: 13 May 2021 Correspondence Address: Chuang, E.Y.; Graduate Institute of Biomedical Electronics and Bioinformatics, Taiwan; email: chuangey@ntu.edu.tw Correspondence Address: Chuang, E.Y.; Bioinformatics and Biostatistics Core, Taiwan; email: chuangey@ntu.edu.tw Correspondence Address: Chuang, E.Y.; Biomedical Technology and Device Research Laboratories, Taiwan; email: chuangey@ntu.edu.tw Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 10617, Taiwan Department of Surgery, Lotung Poh-Ai Hospital, Yilan County, 26546, Taiwan Genome and Systems Biology Degree Program, National Taiwan University, Taipei, 10617, Taiwan Comprehensive Breast Health Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan Bioinformatics and Biostatistics Core, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, 10055, Taiwan Department of Breast Surgery, Dajia Branch, Kuang Tien General Hospital, Taichung, 43761, Taiwan Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan Department of Public Health, National Taiwan University, Taipei, 10055, Taiwan Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan Department of Surgery, National Taiwan University Hospital, Taipei, 10016, Taiwan Institute of Biotechnology, National Taiwan University, Taipei, 10672, Taiwan Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 31057, Taiwan Export Date: 6 June 2021 Correspondence Address: Chuang, E.Y.; Graduate Institute of Biomedical Electronics and Bioinformatics, Taiwan; email: chuangey@ntu.edu.tw Correspondence Address: Chuang, E.Y.; Bioinformatics and Biostatistics Core, Taiwan; email: chuangey@ntu.edu.tw Correspondence Address: Chuang, E.Y.; Biomedical Technology and Device Research Laboratories, Taiwan; email: chuangey@ntu.edu.tw AB - Simple Summary Ipsilateral breast tumor relapse (IBTR) occurs in 5-10% of localized breast cancers (BCs) within 10 years of incidence, despite proper treatment of the primary lesion. However, the clinical consequences of evolutionary trajectories of BC cells and their impact on IBTR remain poorly understood. Here, we conducted a longitudinal genomic analysis of 10 matched localized BC patients with IBTR. Overall, we identified the differences in homologous recombination deficiency, chromosomal instability, and somatic mutation drivers between primary and relapsed lesions. Our analyses highlighted three clonal architectures that shape by distinct mutagenic processes and subclonal diversification during relapse progression. Finally, this study provided a framework, which integrated actionable biomarkers with clonal architectures, towards improvement of future treatment decisions. The evolutionary trajectories that drive clinical and therapeutic consequences in localized breast cancers (BCs) with ipsilateral breast tumor relapse (IBTR) remain largely unknown. Analyses of longitudinal paired whole-exome sequencing data from 10 localized BC patients with IBTR reveal that, compared to primary breast tumors, homologous recombination (HR) deficiency, inactivation of the HR pathway, chromosomal instability, and somatic driver mutations are more frequent. Furthermore, three major models of evolution in IBTR are summarized, through which relative contributions of mutational signatures shift, and the subclonal diversity expansions are shown. Optimal treatment regimens are suggested by the clinically relevant molecular features, such as HR deficiency (20%) or specific alterations (30%) with sensitivity to available FDA-approved drugs. Finally, a rationale for the development of the therapeutic management framework is provided. This study sheds light on the complicated evolution patterns in IBTR and has significant clinical implications for future improvement of treatment decisions. LA - English DB - MTMT ER - TY - JOUR AU - Wu, Jianchun AU - Crowe, David L. TI - PARP5B is required for nonhomologous end joining during tumorigenesis in vivo JF - MOLECULAR CARCINOGENESIS J2 - MOL CARCINOGEN VL - 61 PY - 2021 IS - 1 SP - 85 EP - 98 PG - 14 SN - 0899-1987 DO - 10.1002/mc.23363 UR - https://m2.mtmt.hu/api/publication/32686133 ID - 32686133 N1 - Funding Agency and Grant Number: National Institute of Dental and Craniofacial ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [DE14283] Funding text: National Institute of Dental and Craniofacial Research, Grant/Award Number: DE14283 AB - Poly(ADP-ribose) polymerases (PARP) act as DNA damage sensors that produce poly(ADP-ribose) (PAR) chains at double-strand breaks, facilitating the recruitment of repair factors. Cancers with homologous recombination defects are sensitive to small molecule PARP inhibitors. Despite PARP5B gene copy number changes in many cancers, the effects of this genetic alteration on tumor phenotype are largely unknown. To better understand this clinical finding, we characterized a PARP5B null mutation in a carcinogen-induced in vivo head and neck squamous cell carcinoma (SCC) model. Reduced PARP5B expression inhibited tumor growth, induced primary tumor differentiation and apoptosis, and inhibited cell proliferation and metastasis. Loss of PARP5B expression-induced ataxia telangiectasia and Rad3 related (ATR) activation and depleted the cancer stem cell fraction. PARP5B null tumor cells lacked 53BP1+ double-strand break foci, ATM activation, and p53 induction compared to PARP5B+/+ cancers. PARP5B null SCC expresses a multiprotein complex containing PML, pRPA, Rad50, Rad51, XRCC1, proliferating cell nuclear antigen (PCNA), and Mcm2, suggesting an HR-mediated repair mechanism at DNA replication foci. Low doses of etoposide combined with the PARP5B inhibitor XAV939 induced senescence and apoptosis in human SCC lines. NBS1 overexpression in these cells inhibited the effects of low-dose etoposide/XAV939 treatment. Our results indicate that PARP5B inhibition is new targeted cancer therapy. LA - English DB - MTMT ER - TY - JOUR AU - Xiao, L. AU - Zhou, J. AU - Liu, H. AU - Zhou, Y. AU - Chen, W. AU - Cui, W. AU - Zhao, Y. TI - RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 11 PY - 2021 SN - 2234-943X DO - 10.3389/fonc.2021.679262 UR - https://m2.mtmt.hu/api/publication/32474744 ID - 32474744 N1 - School of Medicine, Xiamen University, Xiamen, China Department of Oncology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China School of Medical Science, Ningbo University, Ningbo, China Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital, Xiamen University, Xiamen, China Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University Affiliated ZhongShan Hospital), Xiamen, China Cited By :4 Export Date: 3 November 2023 Correspondence Address: Cui, W.; School of Medical Science, China Correspondence Address: Zhao, Y.; Department of Oncology and Vascular Interventional Radiology, China Chemicals/CAS: collagenase 3, 175449-82-8; macrophage elastase LA - English DB - MTMT ER - TY - JOUR AU - Zhang, Chenyue AU - Wang, Haiyong TI - The source of the tumor tissue should be taken into consideration when distinguishing tumor mutational burden scores JF - LUNG CANCER J2 - LUNG CANCER-J IASLC VL - 154 PY - 2021 SP - 214 EP - 215 PG - 2 SN - 0169-5002 DO - 10.1016/j.lungcan.2021.02.007 UR - https://m2.mtmt.hu/api/publication/32061900 ID - 32061900 N1 - Funding Agency and Grant Number: Special Funds for Taishan Scholars Project [tsqn201812149]; Academic promotion program of Shandong First Medical University [2019RC004] Funding text: This study was supported jointly by Special Funds for Taishan Scholars Project (Grant No. tsqn201812149), Academic promotion program of Shandong First Medical University (2019RC004). LA - English DB - MTMT ER - TY - JOUR AU - Zhang, Dainan AU - Wang, Xi AU - Ma, Shunchang AU - Li, Peiliang AU - Xue, Fei AU - Mao, Beibei AU - Guan, Xiudong AU - Zhou, Wenjianlong AU - Peng, Jiayi AU - Su, Kun AU - Zhang, Chuanbao AU - Jia, Wang TI - Targeted exome sequencing for the identification of common mutational signatures and potential driver mutations for brain metastases and prognosis JF - ONCOLOGY LETTERS J2 - ONCOL LETT VL - 21 PY - 2021 IS - 3 PG - 8 SN - 1792-1074 DO - 10.3892/ol.2021.12440 UR - https://m2.mtmt.hu/api/publication/32062156 ID - 32062156 N1 - Funding Agency and Grant Number: Capital's Funds for Health Improvement and Research (CFH) [2018-1-1071]; National Natural Science FundNational Natural Science Foundation of China (NSFC) [81701085, U1804199]; Henan Key Laboratory of the Neural Regeneration and Repairment [HNSJXF-2018-001] Funding text: The present study was supported by the Capital's Funds for Health Improvement and Research (CFH; grant no. 2018-1-1071), The National Natural Science Fund (grant nos. 81701085 and U1804199) and the Henan Key Laboratory of the Neural Regeneration and Repairment (grant no. HNSJXF-2018-001). AB - Brain metastases (BMs) are malignancies in the central nervous system with poor prognosis. Genetic landscapes of the primary tumor sites have been extensively profiled; however, mutations associated with BMs are poorly understood. In the present study, target exome sequencing of 560 cancer-associated genes in samples from 52 patients with brain metastasis from various primary sites was performed. Recurrent mutations for BMs from distinct origins were identified. There were both genetic homogeneity and heterogeneity between BMs and primary lung tumor tissues. The mutation rate of the major cancer driver gene, TP53, was consistently high in both the primary lung cancer sites and BMs, while some genetic alterations, associated with DNA damage response deficiency, were specifically enriched in BMs. The mutational signatures enriched in BMs could serve as actionable targets for treatment. The mutation in the primary site of the potential brain metastasis driver gene, nuclear mitotic apparatus protein 1 (NUMA1), affected the progression-free survival time of patients with lung cancer, and patients with the NUMA1 mutation in BMs had a good prognosis. This suggested that the occurrence and clinical outcome of brain metastases could be independent of each other. LA - English DB - MTMT ER - TY - CHAP AU - Chukwueke, U.N. AU - Lee, E.Q. AU - Wen, P.Y. ED - Manmeet, Ahluwalia ED - Philippe, Metellus ED - Riccardo, Soffietti TI - Neurological complications of targeted therapies T2 - Central Nervous System Metastases PB - Springer Netherlands CY - Cham SN - 9783030234171 PY - 2020 SP - 341 EP - 363 PG - 23 DO - 10.1007/978-3-030-23417-1_27 UR - https://m2.mtmt.hu/api/publication/32145170 ID - 32145170 N1 - Export Date: 17 August 2021 LA - English DB - MTMT ER - TY - JOUR AU - de Luca, Xavier M. AU - Newell, Felicity AU - Kazakoff, Stephen H. AU - Hartel, Gunter AU - Reed, Amy E. McCart AU - Holmes, Oliver AU - Xu, Qinying AU - Wood, Scott AU - Leonard, Conrad AU - Pearson, John V AU - Lakhani, Sunil R. AU - Waddell, Nicola AU - Nones, Katia AU - Simpson, Peter T. TI - Using whole-genome sequencing data to derive the homologous recombination deficiency scores JF - NPJ BREAST CANCER J2 - NPJ BREAST CANCER VL - 6 PY - 2020 IS - 1 PG - 8 SN - 2374-4677 DO - 10.1038/s41523-020-0172-0 UR - https://m2.mtmt.hu/api/publication/31717172 ID - 31717172 N1 - Funding Agency and Grant Number: National Health and Medical Research Council (NHMRC, Australia)National Health and Medical Research Council of Australia; National Breast Cancer Foundation (NBCF) Australia; Cancer Australia; NBCF Australia; NHMRCNational Health and Medical Research Council of Australia; Queensland Cancer Fund; Cancer Council of South AustraliaCancer Council South Australia; Cancer Foundation of Western AustraliaCancer Council Western Australia; NHMRC AustraliaNational Health and Medical Research Council of Australia [APP1080985, APP1164770]; Keith Boden fellowship; Cancer Council of New South WalesCancer Council New South Wales; Cancer Council of VictoriaCanadian Institutes of Health Research (CIHR)Cancer Council Victoria; Cancer Council of TasmaniaCancer Council Tasmania; NHMRCNational Health and Medical Research Council of Australia [APP1139071] Funding text: We wish to thank all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which have received funding from the National Health and Medical Research Council (NHMRC, Australia), the National Breast Cancer Foundation (NBCF) Australia, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by a grant from the NBCF Australia, and previously by the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. We also thank patients and staff who contributed to the Australian Breast Cancer Tissue Bank and the Brisbane Breast Bank. We acknowledge the support of Metro North Hospital and Health Services in the collection of the Clinical Subject Data and Clinical Subject Materials. The work was funded by NHMRC Australia project grants (APP1080985 and APP1164770). K.N. is supported by Keith Boden fellowship. N.W. is supported with an NHMRC senior research fellowship (APP1139071). Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia Pathology Queensland, Royal Brisbane & Women’s Hospital, Brisbane, QLD, Australia Cited By :1 Export Date: 13 May 2021 Correspondence Address: Simpson, P.T.; Centre for Clinical Research, Australia; email: p.simpson@uq.edu.au AB - The homologous recombination deficiency (HRD) score was developed using whole-genome copy number data derived from arrays as a way to infer deficiency in the homologous recombination DNA damage repair pathway (in particularBRCA1orBRCA2deficiency) in breast cancer samples. The score has utility in understanding tumour biology and may be indicative of response to certain therapeutic strategies. Studies have used whole-exome sequencing to derive the HRD score, however, with increasing use of whole-genome sequencing (WGS) to characterise tumour genomes, there has yet to be a comprehensive comparison between HRD scores derived by array versus WGS. Here we demonstrate that there is both a high correlation and a good agreement between array- and WGS-derived HRD scores and between the scores derived from WGS and downsampled WGS to represent shallow WGS. For samples with an HRD score close to threshold for stratifying HR proficiency or deficiency there was however some disagreement in the HR status between array and WGS data, highlighting the importance of not relying on a single method of ascertaining the homologous recombination status of a tumour. LA - English DB - MTMT ER - TY - JOUR AU - Ladányi, Andrea AU - Tímár, József TI - Immunologic and immunogenomic aspects of tumor progression JF - SEMINARS IN CANCER BIOLOGY J2 - SEMIN CANCER BIOL VL - 60 PY - 2020 SP - 249 EP - 261 PG - 13 SN - 1044-579X DO - 10.1016/j.semcancer.2019.08.011 UR - https://m2.mtmt.hu/api/publication/30883383 ID - 30883383 LA - English DB - MTMT ER - TY - JOUR AU - Cheasley, Dane AU - Li, Na AU - Rowley, Simone M. AU - Elder, Kenneth AU - Mann, G. Bruce AU - Loi, Sherene AU - Savas, Peter AU - Goode, David L. AU - Kader, Tanjina AU - Zethoven, Magnus AU - Semple, Tim AU - Fox, Stephen B. AU - Pang, Jia-Min AU - Byrne, David AU - Devereux, Lisa AU - Nickson, Carolyn AU - Procopio, Pietro AU - Lee, Grant AU - Hughes, Siobhan AU - Saunders, Hugo AU - Fujihara, Kenji M. AU - Kuykhoven, Keilly AU - Connaughton, Jacquie AU - James, Paul A. AU - Gorringe, Kylie L. AU - Campbell, Ian G. TI - Molecular comparison of interval and screen-detected breast cancers JF - JOURNAL OF PATHOLOGY J2 - J PATHOL VL - 248 PY - 2019 IS - 2 SP - 243 EP - 252 PG - 10 SN - 0022-3417 DO - 10.1002/path.5251 UR - https://m2.mtmt.hu/api/publication/30956606 ID - 30956606 N1 - Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia Department of Surgery, University of Melbourne, Melbourne, VIC, Australia The Royal Melbourne and Royal Women's Hospitals, Parkville, VIC, Australia The Edinburgh Breast Unit, Western General Hospital, Edinburgh, United Kingdom Division of Clinical Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Bioinformatics Consulting Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Genomics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Department of Pathology, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne, VIC, Australia Lifepool, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia Cancer Genetics and Genomics Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Export Date: 11 December 2019 CODEN: JPTLA Correspondence Address: Campbell, I.G.; Cancer Genetics Laboratory, Peter MacCallum Cancer CentreAustralia; email: ian.campbell@petermac.org Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia Department of Surgery, University of Melbourne, Melbourne, VIC, Australia The Royal Melbourne and Royal Women's Hospitals, Parkville, VIC, Australia The Edinburgh Breast Unit, Western General Hospital, Edinburgh, United Kingdom Division of Clinical Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Bioinformatics Consulting Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Genomics Core, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Department of Pathology, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne, VIC, Australia Lifepool, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia Cancer Genetics and Genomics Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Export Date: 15 January 2020 CODEN: JPTLA Correspondence Address: Campbell, I.G.; Cancer Genetics Laboratory, Peter MacCallum Cancer CentreAustralia; email: ian.campbell@petermac.org AB - Breast cancer (BC) diagnosed after a negative mammogram but prior to the next screening episode is termed an 'interval BC' (IBC). Understanding the molecular differences between IBC and screen-detected BCs (SDBC) could improve mammographic screening and management options. Therefore, we assessed both germline and somatic genomic aberrations in a prospective cohort. Utilising the Lifepool cohort of >54 000 women attending mammographic screening programs, 930 BC cases with screening status were identified (726 SDBC and 204 IBC). Clinico-pathological and family history information were recorded. Germline and tumour DNA were collected where available and sequenced for BC predisposition and driver gene mutations. Compared to SDBC, IBCs were significantly associated with a younger age at diagnosis and tumour characteristics associated with worse prognosis. Germline DNA assessment of BC cases that developed post-enrolment (276 SDBCs and 77 IBCs) for pathogenic mutations in 12 hereditary BC predisposition genes identified 8 carriers (2.27%). The germline mutation frequency was higher in IBC versus SDBC, although not statistically significant (3.90% versus 1.81%, p = 0.174). Comparing somatic genetic features of IBC and SDBC matched for grade, histological subtype and hormone receptor revealed no significant differences, with the exception of higher homologous recombination deficiency scores in IBC, and copy number changes on chromosome Xq in triple negative SDBCs. Our data demonstrates that while IBCs are clinically more aggressive than SDBC, when matched for confounding clinico-pathological features they do not represent a unique molecular class of invasive BC, but could be a consequence of timing of tumour initiation and mammographic screening. Copyright (c) 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. LA - English DB - MTMT ER - TY - JOUR AU - Diossy, M AU - Reiniger, Lilla AU - Sztupinszki, Zsófia AU - Krzystanek, M AU - Timms, K M AU - Neff, C AU - Solimeno, C AU - Pruss, D AU - Eklund, A C AU - Tóth, Erika AU - Kiss, O AU - Rusz, O AU - Cserni, G AU - Zombori, Tamás AU - Székely, Borbála AU - Kulka, Janina AU - Tímár, J AU - Csabai, István AU - Szállási, Zoltán TI - Corrigendum to: Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors JF - ANNALS OF ONCOLOGY J2 - ANN ONCOL VL - 30 PY - 2019 IS - 8 SP - 1406 EP - 1406 PG - 1 SN - 0923-7534 DO - 10.1093/annonc/mdz081 UR - https://m2.mtmt.hu/api/publication/30625426 ID - 30625426 LA - English DB - MTMT ER - TY - JOUR AU - Jerez, Y. AU - Márquez-Rodas, I. AU - Aparicio, I. AU - Alva, M. AU - Martín, M. AU - López-Tarruella, S. TI - Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations JF - DRUGS J2 - DRUGS VL - 80 PY - 2019 IS - 2 SP - 131 EP - 146 PG - 16 SN - 0012-6667 DO - 10.1007/s40265-019-01235-5 UR - https://m2.mtmt.hu/api/publication/31127339 ID - 31127339 N1 - Medical Oncology Service, Departamento de Medicina, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, CiberOnc, Madrid, Spain Export Date: 15 January 2020 CODEN: DRUGA Correspondence Address: Martín, M.; Medical Oncology Service, Departamento de Medicina, Hospital General Universitario Gregorio MarañónSpain; email: mmartin@geicam.org LA - English DB - MTMT ER - TY - JOUR AU - Lim, Malcolm AU - Puttick, Simon AU - Houston, Zachary AU - Thurecht, Kristofer AU - Kalita-de Croft, Priyakshi AU - Mahler, Stephen AU - Rose, Stephen AU - Jeffree, Rosalind AU - Mazzieri, Roberta AU - Dolcetti, Riccardo AU - Lakhani, Sunil AU - Saunus, Jodi TI - Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 6 PG - 24 SN - 1661-6596 DO - 10.3390/ijms20061280 UR - https://m2.mtmt.hu/api/publication/30622858 ID - 30622858 N1 - Funding Agency and Grant Number: Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [APP1113867] Funding text: This work was supported by program funding to S.R.L. from the Australian National Health and Medical Research Council (APP1113867). AB - Brain metastases are the most prevalent of intracranial malignancies. They are associated with a very poor prognosis and near 100% mortality. This has been the case for decades, largely because we lack effective therapeutics to augment surgery and radiotherapy. Notwithstanding improvements in the precision and efficacy of these life-prolonging treatments, with no reliable options for adjunct systemic therapy, brain recurrences are virtually inevitable. The factors limiting intracranial efficacy of existing agents are both physiological and molecular in nature. For example, heterogeneous permeability, abnormal perfusion and high interstitial pressure oppose the conventional convective delivery of circulating drugs, thus new delivery strategies are needed to achieve uniform drug uptake at therapeutic concentrations. Brain metastases are also highly adapted to their microenvironment, with complex cross-talk between the tumor, the stroma and the neural compartments driving speciation and drug resistance. New strategies must account for resistance mechanisms that are frequently engaged in this milieu, such as HER3 and other receptor tyrosine kinases that become induced and activated in the brain microenvironment. Here, we discuss molecular and physiological factors that contribute to the recalcitrance of these tumors, and review emerging therapeutic strategies, including agents targeting the PI3K axis, immunotherapies, nanomedicines and MRI-guided focused ultrasound for externally controlling drug delivery. LA - English DB - MTMT ER - TY - JOUR AU - Nassiri, Farshad AU - Aldape, Kenneth AU - Alhuwalia, Manmeet AU - Brastianos, Priscilla AU - Ducray, Francois AU - Galldiks, Norbert AU - Kim, Albert AU - Lamszus, Katrin AU - Mitchell, Duane AU - Nabors, L. Burt AU - Nam, Do-Hyun AU - Natsume, Atsushi AU - Ng, Ho-Keung AU - Niclou, Simone AU - Sahm, Felix AU - Short, Susan AU - Walsh, Kyle AU - Wick, Wolfgang AU - Zadeh, Gelareh TI - Highlights of the inaugural ten - the launch of Neuro-Oncology Advances JF - NEURO-ONCOLOGY ADVANCES J2 - NEUROONCOL ADV VL - 1 PY - 2019 IS - 1 PG - 5 SN - 2632-2498 DO - 10.1093/noajnl/vdz016 UR - https://m2.mtmt.hu/api/publication/33364480 ID - 33364480 N1 - Division of Neurosurgery, University Health Network and MacFeeters-Hamilton Neuro-Oncology Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States Divisions of Hematology/Oncology and Neuro-Oncology, Departments of Medicine and Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States Department of Neuro-Oncology, Hospices Civils de Lyon, Lyon, France Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany Institute of Neuroscience and Medicine (INM-3), Research Center Juelich, Juelich and Germany Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Duesseldorf, Germany Department of Neurosurgery, School of Medicine, Washington University, St. Louis, MO, United States Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Lillian S. Wells Department of Neurosurgery, UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, FL, United States Department of Neurology, University of Alabama, Birmingham, Birmingham, AL, United States Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea Department of Neurosurgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg Leeds Institute of Cancer and Pathology, Faculty of Medicine and Health, University of Leeds, St James's University Hospital, West Yorkshire, Leeds, United Kingdom Duke Cancer Institute, Duke University, Durham, NC, United States University Medical Center, German Cancer Research Center Heidelberg, Germany Export Date: 1 June 2023 LA - English DB - MTMT ER - TY - JOUR AU - Sambade, Maria J. AU - Van, Swearingen Amanda E. D. AU - McClure, Marni B. AU - Deal, Allison M. AU - Santos, Charlene AU - Sun, Kaiming AU - Wang, Jing AU - Mikule, Keith AU - Anders, Carey K. TI - Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wild-type intracranial triple-negative breast cancer murine models JF - NEURO-ONCOLOGY ADVANCES J2 - NEUROONCOL ADV VL - 1 PY - 2019 IS - 1 PG - 11 SN - 2632-2498 DO - 10.1093/noajnl/vdz005 UR - https://m2.mtmt.hu/api/publication/33364481 ID - 33364481 N1 - Funding Agency and Grant Number: NCI Center Core Support Grant [CA16086] Funding text: The authors thank Dr. Toshiyuki Yoneda (Osaka University) for providing MDA-MB-231Br cells. Animal studies were performed within the Animal Studies Core Facility, supported in part by an NCI Center Core Support Grant (CA16086) to the Lineberger Comprehensive Cancer Center. AB - Background Despite the poor prognosis of triple-negative breast cancer (TNBC) brain metastases, there are no approved systemic therapies. We explored the DNA-damaging poly(ADP-ribose) polymerase inhibitor (PARPi) niraparib in intracranial mouse models of breast cancer susceptibility protein (BRCA)-mutant TNBC. Methods Mice bearing intracranial human-derived TNBC cell lines (SUM149, MDA-MB-231Br, or MDA-MB-436) were treated with niraparib and monitored for survival; intracranial tissues were analyzed for PAR levels and niraparib concentration by mass spectrometry. RNASeq data of primary breast cancers using The Cancer Genome Atlas were analyzed for DNA damage signatures. Combined RAD51 and PARP inhibition in TNBC cell lines was assessed in vitro by colony-forming assays. Results Daily niraparib increased median survival and decreased tumor burden in the BRCA-mutant MDA-MB-436 model, but not in the BRCA-mutant SUM149 or BRCA-wild-type MDA-MB-231Br models despite high concentrations in intracranial tumors. RAD51 inhibitor B02 was shown to sensitize all cell lines to PARP inhibition (PARPi). In the analysis of BRCA-mutant primary human TNBCs, gene expression predictors of PARPi sensitivity and DNA repair signatures demonstrate widespread heterogeneity, which may explain the differential response to PARPi. Interestingly, these signatures are significantly correlated to RAD51 expression including PARPi sensitivity (R-2 = 0.602, R-2= 0.758). Conclusions Niraparib penetrates intracranial tumor tissues in mouse models of TNBC with impressive single-agent efficacy in BRCA-mutant MDA-MB-436. Clinical evaluation of niraparib to treat TNBC brain metastases, an unmet clinical need desperate for improved therapies, is warranted. Further compromising DNA repair through RAD51 inhibition may further augment TNBC's response to PARPi. LA - English DB - MTMT ER - TY - JOUR AU - Shreenivas, Aditya AU - Shapiro, Charles L. TI - Central nervous system metastases in triple-negative breast cancer: A step in the right direction JF - BREAST JOURNAL J2 - BREAST J VL - 25 PY - 2019 IS - 3 SP - 361 EP - 362 PG - 2 SN - 1075-122X DO - 10.1111/tbj.13232 UR - https://m2.mtmt.hu/api/publication/30981375 ID - 30981375 N1 - Export Date: 2 November 2021 CODEN: BRJOF Correspondence Address: Shapiro, C.L.; Division of Hematology and Oncology, United States; email: charles.shapiro@mssm.edu LA - English DB - MTMT ER - TY - JOUR AU - Song, Y. AU - Barry, W.T. AU - Seah, D.S. AU - Tung, N.M. AU - Garber, J.E. AU - Lin, N.U. TI - Patterns of recurrence and metastasis in BRCA1/BRCA2-associated breast cancers JF - CANCER J2 - CANCER-AM CANCER SOC VL - 126 PY - 2019 IS - 2 SP - 271 EP - 280 PG - 10 SN - 0008-543X DO - 10.1002/cncr.32540 UR - https://m2.mtmt.hu/api/publication/30981406 ID - 30981406 N1 - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Harvard Medical School, Boston, MA, United States Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Boston, MA, United States Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States School of Medicine, University of Notre Dame, Sydney, Australia St. Vincent's Clinical School, University of New South WalesNSW, Australia Cited By :22 Export Date: 2 November 2021 CODEN: CANCA Correspondence Address: Lin, N.U.; Department of Medical Oncology, United States; email: nancy_lin@dfci.harvard.edu LA - English DB - MTMT ER - TY - JOUR AU - Tang, Dongyang AU - Zhao, Xin AU - Zhang, Li AU - Wang, Zhiwei AU - Wang, Cheng TI - Identification of hub genes to regulate breast cancer metastasis to brain by bioinformatics analyses JF - JOURNAL OF CELLULAR BIOCHEMISTRY J2 - J CELL BIOCHEM VL - 120 PY - 2019 IS - 6 SP - 9522 EP - 9531 PG - 10 SN - 0730-2312 DO - 10.1002/jcb.28228 UR - https://m2.mtmt.hu/api/publication/30622857 ID - 30622857 N1 - Department of Experimental Management Center, Henan Institute of Science and Technology, Xinxiang, China Department of Pharmacy, Xinxiang Central Hospital, Xinxiang, China Department of architecture, College of Horticulture and Landscape Architecture, Henan Institute of Science and Technology, Xinxiang, China Department of pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China Cited By :11 Export Date: 11 December 2019 CODEN: JCEBD Correspondence Address: Tang, D.; Department of Experimental Management Center, Henan Institute of Science and TechnologyChina; email: dy_tang@hist.edu.cn Department of Experimental Management Center, Henan Institute of Science and Technology, Xinxiang, China Department of Pharmacy, Xinxiang Central Hospital, Xinxiang, China Department of architecture, College of Horticulture and Landscape Architecture, Henan Institute of Science and Technology, Xinxiang, China Department of pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China Cited By :13 Export Date: 15 January 2020 CODEN: JCEBD Correspondence Address: Tang, D.; Department of Experimental Management Center, Henan Institute of Science and TechnologyChina; email: dy_tang@hist.edu.cn LA - English DB - MTMT ER - TY - JOUR AU - Tímár, József AU - Ladányi, Andrea TI - A tumorprogresszió immungenomikai aspektusai [A Immunogenomic aspects of tumor progression] JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 63 PY - 2019 IS - 3 SP - 173 EP - 182 PG - 10 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/30855311 ID - 30855311 N1 - Export Date: 15 January 2020 CODEN: MGONA Correspondence Address: József, T.; Semmelweis Egyetem, II. Sz. Patológiai Intézet, Üllői út 93, Hungary; email: jtimar@gmail.com LA - Hungarian DB - MTMT ER - TY - JOUR AU - Tyran, Marguerite AU - Carbuccia, Nadine AU - Garnier, Severine AU - Guille, Arnaud AU - Adelaide, Jose AU - Finetti, Pascal AU - Touzlian, Julien AU - Viens, Patrice AU - Tallet, Agnes AU - Goncalves, Anthony AU - Metellus, Philippe AU - Birnbaum, Daniel AU - Chaffanet, Max AU - Bertucci, Francois TI - A Comparison of DNA Mutation and Copy Number Profiles of Primary Breast Cancers and Paired Brain Metastases for Identifying Clinically Relevant Genetic Alterations in Brain Metastases JF - CANCERS J2 - CANCERS VL - 11 PY - 2019 IS - 5 PG - 18 SN - 2072-6694 DO - 10.3390/cancers11050665 UR - https://m2.mtmt.hu/api/publication/30914154 ID - 30914154 N1 - Laboratoire d’Oncologie Prédictive, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, F-13009, France Département de Radiothérapie, Institut Paoli-Calmettes, Marseille, 13009, France Département d’Anatomopathologie, Institut Paoli-Calmettes, Marseille, 13009, France Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille, 13009, France Faculté de Médecine, Aix-Marseille Université, Marseille, 13005, France Département de Neurochirurgie et de Neuro-oncologie, Hôpital Privé Clairval, Ramsay-Générale de Santé and Institut de Neurophysiopathologie Equipe 10, UMR0751, CNRS, Marseille, 13009, France Cited By :2 Export Date: 11 December 2019 Correspondence Address: Bertucci, F.; Laboratoire d’Oncologie Prédictive, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-CalmettesFrance; email: bertuccif@ipc.unicancer.fr Laboratoire d’Oncologie Prédictive, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, F-13009, France Département de Radiothérapie, Institut Paoli-Calmettes, Marseille, 13009, France Département d’Anatomopathologie, Institut Paoli-Calmettes, Marseille, 13009, France Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille, 13009, France Faculté de Médecine, Aix-Marseille Université, Marseille, 13005, France Département de Neurochirurgie et de Neuro-oncologie, Hôpital Privé Clairval, Ramsay-Générale de Santé and Institut de Neurophysiopathologie Equipe 10, UMR0751, CNRS, Marseille, 13009, France Cited By :2 Export Date: 15 January 2020 Correspondence Address: Bertucci, F.; Laboratoire d’Oncologie Prédictive, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-CalmettesFrance; email: bertuccif@ipc.unicancer.fr AB - Improving the systemic treatment of brain metastases (BM) in primary breast cancer (PBC) is impaired by the lack of genomic characterization of BM. To estimate the concordance of DNA copy-number-alterations (CNAs), mutations, and actionable genetic alterations (AGAs) between paired samples, we performed whole-genome array-comparative-genomic-hybridization, and targeted-next-generation-sequencing on 14 clinical PBC-BM pairs. We found more CNAs, more mutations, and higher tumor mutational burden, and more AGAs in BM than in PBC; 92% of the pairs harbored at least one AGA in the BM not observed in the paired PBC. This concerned various therapeutic classes, including tyrosine-kinase-receptor-inhibitors, phosphatidylinositol 3-kinase/AKT/mammalian Target of Rapamycin (PI3K/AKT/MTOR)-inhibitors, poly ADP ribose polymerase (PARP)-inhibitors, or cyclin-dependent kinase (CDK)-inhibitors. With regards to the PARP-inhibitors, the homologous recombination defect score was positive in 79% of BM, compared to 43% of PBC, discordant in 7 out of 14 pairs, and positive in the BM in 5 out of 14 cases. CDK-inhibitors were associated with the largest percentage of discordant AGA appearing in the BM. When considering the AGA with the highest clinical-evidence level, for each sample, 50% of the pairs harbored an AGA in the BM not detected or not retained from the analysis of the paired PBC. Thus, the profiling of BM provided a more reliable opportunity, than that of PBC, for diagnostic decision-making based on genomic analysis. Patients with BM deserve an investigation of several targeted therapies. LA - English DB - MTMT ER -