Author
Judith Balmaña
Other affiliations: Autonomous University of Barcelona
Bio: Judith Balmaña is an academic researcher from Hebron University. The author has contributed to research in topics: Breast cancer & Medicine. The author has an hindex of 47, co-authored 177 publications receiving 9058 citations. Previous affiliations of Judith Balmaña include Autonomous University of Barcelona.
Topics: Breast cancer, Medicine, Cancer, Germline mutation, Population
Papers published on a yearly basis
Papers
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TL;DR: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations, and warrants further investigation in confirmatory studies.
Abstract: Purpose Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) –associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. Patients and Methods This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. Results A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to...
1,423 citations
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Martin Luther University of Halle-Wittenberg1, Katholieke Universiteit Leuven2, Eppendorf (Germany)3, The Catholic University of America4, Karolinska Institutet5, Uppsala University6, Leiden University Medical Center7, Hebron University8, Radboud University Nijmegen9, Seconda Università degli Studi di Napoli10, University of São Paulo11, University of Oxford12, Medical University of Vienna13, Autonomous University of Barcelona14, Sheba Medical Center15, Ain Shams University16, Clínica Alemana17, Mount Vernon Hospital18, Bank of Cyprus19, Odense University Hospital20, University of Crete21, Marmara University22, University of Valencia23
TL;DR: This ESMO guideline is recommended to be used as the basis for treatment and management decisions, delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations.
1,299 citations
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Guy's Hospital1, Harvard University2, Tel Aviv University3, University of Milan4, Breast International Group5, University of Pittsburgh6, University of Pennsylvania7, Université libre de Bruxelles8, AstraZeneca9, National Institutes of Health10, Sahlgrenska University Hospital11, Gdańsk Medical University12, Kaiser Permanente13, Fudan University14, Northside Hospital15, Curie Institute16, Pomeranian Medical University17, University of California, Los Angeles18, Goethe University Frankfurt19, Medical University of Vienna20, Merck & Co.21, University of Queensland22
TL;DR: In this paper, a poly(adenosine diphosphate-ribose) polymerase inhibitor was proposed to target cancers with defects in homologous recombination repair by synthetic lethality.
Abstract: Background Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduc...
530 citations
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TL;DR: It is estimated that the breast cancer lifetime risks for the5% of BRCA1 carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk, and the ovarian cancer lifetime risk is 63% or higher, based on the known cancer risk-modifying loci.
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
417 citations
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TL;DR: The combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1-related breast cancers, making this a candidate combination to be tested in human clinical trials.
Abstract: There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in a MMTV-Cre Brca1f/fTrp53 +/− mouse model of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation, and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK pathway at the “pushing margin.” Surprisingly, PI3K inhibition increased indicators of DNA damage, poly-ADP-ribosylation (PAR), and γ-H2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. The PARP inhibitor olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and olaparib delayed tumor doubling to more than 70 days in the mouse model and more than 50 days in xenotransplants from human BRCA1 -related tumors, suggesting that combined PI3K and PARP inhibition might be an effective treatment of BRCA1 -related tumors.
Significance: Current treatment options for triple-negative breast cancer are limited to chemotherapeutic regimens that have considerable toxicity and are not curative. We report here that the combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1 -related breast cancers, making this a candidate combination to be tested in human clinical trials. Cancer Discov; 2(11); 1048–63. ©2012 AACR .
Read the Commentary on this article by Rehman et al., [p. 982][1].
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379 citations
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01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations
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TL;DR: Improved data access is improved with the release of a new RESTful API to support high-throughput programmatic access, an improved web interface and a new summary statistics database.
Abstract: The GWAS Catalog delivers a high-quality curated collection of all published genome-wide association studies enabling investigations to identify causal variants, understand disease mechanisms, and establish targets for novel therapies. The scope of the Catalog has also expanded to targeted and exome arrays with 1000 new associations added for these technologies. As of September 2018, the Catalog contains 5687 GWAS comprising 71673 variant-trait associations from 3567 publications. New content includes 284 full P-value summary statistics datasets for genome-wide and new targeted array studies, representing 6 × 109 individual variant-trait statistics. In the last 12 months, the Catalog's user interface was accessed by ∼90000 unique users who viewed >1 million pages. We have improved data access with the release of a new RESTful API to support high-throughput programmatic access, an improved web interface and a new summary statistics database. Summary statistics provision is supported by a new format proposed as a community standard for summary statistics data representation. This format was derived from our experience in standardizing heterogeneous submissions, mapping formats and in harmonizing content. Availability: https://www.ebi.ac.uk/gwas/.
2,878 citations
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European Institute of Oncology1, Harvard University2, University of Sydney3, Institut Jules Bordet4, Kantonsspital St. Gallen5, University of St. Gallen6, Loyola University Chicago7, Institut Gustave Roussy8, Karolinska Institutet9, University of Bordeaux10, University of Geneva11, University of Pittsburgh12, University of Copenhagen13, University of Newcastle14, Medical University of Vienna15, University of Toronto16, University of Michigan17, Memorial Sloan Kettering Cancer Center18, Mayo Clinic19, Gdańsk Medical University20, University of Gothenburg21, Baylor College of Medicine22, University of North Carolina at Chapel Hill23, Université libre de Bruxelles24, Netherlands Cancer Institute25, Fudan University26, Kyoto University27, King's College London28, University of Göttingen29, Emory University30
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.
2,831 citations
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2,777 citations
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University of Michigan1, Massachusetts Institute of Technology2, Harvard University3, Memorial Sloan Kettering Cancer Center4, University of Washington5, The Royal Marsden NHS Foundation Trust6, Institute of Cancer Research7, Cornell University8, Brigham and Women's Hospital9, Beth Israel Deaconess Medical Center10, University of Washington Medical Center11, University of Trento12, Wayne State University13, Johns Hopkins University14
TL;DR: This cohort study provides clinically actionable information that could impact treatment decisions for affected individuals and identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF.
2,713 citations