FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2155574915> ?p ?o ?g. }

• W2155574915 endingPage "1869" @default.
• W2155574915 startingPage "1867" @default.
• W2155574915 abstract "The development of drug-biomarker combinations holds promise for tailoring treatment for patients with cancer on the basis of the biology of the tumor exemplified by estrogen receptor expression and blockade and human epidermal growth factor receptor 2 targeting. Approximately 85% of breast cancers have a target for therapy, but triple-negative breast cancers (TNBCs) do not. Although trials have focused on identifying the most efficacious anticancer drug (regimen) for this subtype, it may be that predictive biomarkers are required to guide treatment choices because of the intrinsic heterogeneity of TNBCs. Molecular characterizations have demonstrated a strong association between TNBCs and BRCA1 mutations. Preclinical mechanistic insight indicated that tumor cells with a defect in BRCA1 have impaired homologous recombination (HR), the only error-free pathway of repair of interstrand crosslinks. Cells with impaired HR display sensitivity to agents that induce such lesions. In the general breast cancer population, platinum agents that cause interstrand crosslinks are not preferred over other treatment regimens. However, given the possibility that TNBCs are enriched for such a targetable HR deficiency (HRD), platinum has attracted renewed interest as has been shown in recently published articles. Furthermore, TNBCs may be enriched for BRCA1 mutations and also for a larger group of nonmutated tumors that exhibit HRD. The use of platinum in TNBCs with biomarker analyses has been investigated in the two articles that accompany this editorial. Telli et al neoadjuvantly treated patients with triple-negative or BRCA1/ 2-associated breast cancer with a regimen containing gemcitabine, carboplatin, and iniparib in the PrECOG 0105 trial. Overall, a pathologic complete remission rate of 36% and acceptable toxicity of the regimen were reported. Isakoff et al conducted a phase II trial with cisplatin or carboplatin in patients with metastatic TNBC (TBCRC009; Platinum for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response). The overall response rate was 25%. Both studies reproduce previous findings of efficacy of a platinum-based regimen or platinum alone in TNBC. However, only a subset of patients in these trials derived clinical benefit. Therefore, secondary investigations may help identify biomarkers that associate with a preferential benefit from use of a platinum regimen, which may help guide therapy decisions. Both studies report their analysis of BRCA germline mutation status as well as potential biomarkers for assessing HRD, specifically the HRD loss of heterozygosity (HRD-LOH) score and the HRD large-scale transition (HRD-LST) score. Both markers evaluate so-called genomic scars as signatures of aberrations that can be observed from singlenucleotide polymorphism array–based sequencing or similar technologies and that are associated with defects in error-free repair of interstrand crosslinks. The HRD-LOH score counts the numbers of LOH regions larger than 15 MB but smaller than chromosome size, whereas the HRD-LST score counts the number of breaks between adjacent segments of at least 10 MB. Cutoffs were trained to best separate tumors that had a known deleterious aberration in BRCA1/2 from those that did not. In both studies, patients with a BRCA germline mutation had higher response rates than the general cohort, and the HRD scores highly correlated with BRCA1/2 germline mutations and response rates. In addition, Telli et al identified BRCA1 methylation in nonmutated tumors with high HRD-LOH score, which suggests that these scores identify a subgroup of patients who could benefit from therapy that targets their HRD. Unfortunately, single-arm phase II studies do not allow proper evaluation of a biomarker as a predictor of response to therapy, and they offer limited insight on how to exploit the observed association with outcome of BRCA-associated biomarkers (Fig 1). Thus, the studies by Telli et al and Isakoff et al join several other articles published over the last decade that have reported on the potential promise of BRCA-associated HRD biomarkers but did not provide definitive data on clinical utility. It has been established that the optimal biomarker trial design requires biomarker-positive and -negative patients and patients who have been treated with and without the therapy of interest to evaluate both prognostic and predictive signals. If not included in the phase II design, such a control group could be added. Hence, the lack of a control arm in these two new studies is indeed a major limitation of their findings. In contrast, the TNT trial (Triple Negative Breast Cancer Trial, recently reported as an abstract) was able to more appropriately evaluate the use of HRD biomarkers, at least in patients with advanced disease. In that trial, patients with locally advanced or metastatic TNBC were randomly assigned to therapy with carboplatin at area under the [concentration-time] curve 6 or standardof-care docetaxel. Of great interest, among the 376 patients in that study, 29 were known to be BRCA1 or BRCA2 mutation carriers (including 13 who had estrogen receptor–positive, HER2-negative disease). Prespecified analyses specifically addressed populations JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 17 JUNE 1" @default.
• W2155574915 created "2016-06-24" @default.
• W2155574915 creator A5038684427 @default.
• W2155574915 creator A5063917865 @default.
• W2155574915 date "2015-06-10" @default.
• W2155574915 modified "2023-10-02" @default.
• W2155574915 title "Challenges in the Use of DNA Repair Deficiency As a Biomarker in Breast Cancer" @default.
• W2155574915 cites W1523531555 @default.
• W2155574915 cites W1961026612 @default.
• W2155574915 cites W1966267239 @default.
• W2155574915 cites W1975570360 @default.
• W2155574915 cites W1995224853 @default.
• W2155574915 cites W1996153041 @default.
• W2155574915 cites W2004125597 @default.
• W2155574915 cites W2005558949 @default.
• W2155574915 cites W2045521109 @default.
• W2155574915 cites W2059365987 @default.
• W2155574915 cites W2073618702 @default.
• W2155574915 cites W2074952360 @default.
• W2155574915 cites W2077436902 @default.
• W2155574915 cites W2081562657 @default.
• W2155574915 cites W2086064725 @default.
• W2155574915 cites W2096283457 @default.
• W2155574915 cites W2096745115 @default.
• W2155574915 cites W2097482525 @default.
• W2155574915 cites W2100419317 @default.
• W2155574915 cites W2105265201 @default.
• W2155574915 cites W2105496345 @default.
• W2155574915 cites W2109772731 @default.
• W2155574915 cites W2113499049 @default.
• W2155574915 cites W2113734556 @default.
• W2155574915 cites W2125094267 @default.
• W2155574915 cites W2127262170 @default.
• W2155574915 cites W2128740744 @default.
• W2155574915 cites W2133258471 @default.
• W2155574915 cites W2147208780 @default.
• W2155574915 cites W2147629880 @default.
• W2155574915 cites W2165385395 @default.
• W2155574915 cites W2168409298 @default.
• W2155574915 cites W2168523417 @default.
• W2155574915 cites W2318605753 @default.
• W2155574915 cites W2335140550 @default.
• W2155574915 doi "https://doi.org/10.1200/jco.2014.60.5501" @default.
• W2155574915 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25918281" @default.
• W2155574915 hasPublicationYear "2015" @default.
• W2155574915 type Work @default.
• W2155574915 sameAs 2155574915 @default.
• W2155574915 citedByCount "13" @default.
• W2155574915 countsByYear W21555749152016 @default.
• W2155574915 countsByYear W21555749152017 @default.
• W2155574915 countsByYear W21555749152020 @default.
• W2155574915 countsByYear W21555749152022 @default.
• W2155574915 countsByYear W21555749152023 @default.
• W2155574915 crossrefType "journal-article" @default.
• W2155574915 hasAuthorship W2155574915A5038684427 @default.
• W2155574915 hasAuthorship W2155574915A5063917865 @default.
• W2155574915 hasConcept C121608353 @default.
• W2155574915 hasConcept C126322002 @default.
• W2155574915 hasConcept C134935766 @default.
• W2155574915 hasConcept C143998085 @default.
• W2155574915 hasConcept C2781197716 @default.
• W2155574915 hasConcept C530470458 @default.
• W2155574915 hasConcept C54355233 @default.
• W2155574915 hasConcept C552990157 @default.
• W2155574915 hasConcept C71924100 @default.
• W2155574915 hasConcept C86803240 @default.
• W2155574915 hasConceptScore W2155574915C121608353 @default.
• W2155574915 hasConceptScore W2155574915C126322002 @default.
• W2155574915 hasConceptScore W2155574915C134935766 @default.
• W2155574915 hasConceptScore W2155574915C143998085 @default.
• W2155574915 hasConceptScore W2155574915C2781197716 @default.
• W2155574915 hasConceptScore W2155574915C530470458 @default.
• W2155574915 hasConceptScore W2155574915C54355233 @default.
• W2155574915 hasConceptScore W2155574915C552990157 @default.
• W2155574915 hasConceptScore W2155574915C71924100 @default.
• W2155574915 hasConceptScore W2155574915C86803240 @default.
• W2155574915 hasIssue "17" @default.
• W2155574915 hasLocation W21555749151 @default.
• W2155574915 hasLocation W21555749152 @default.
• W2155574915 hasOpenAccess W2155574915 @default.
• W2155574915 hasPrimaryLocation W21555749151 @default.
• W2155574915 hasRelatedWork W1965261620 @default.
• W2155574915 hasRelatedWork W1979901014 @default.
• W2155574915 hasRelatedWork W2050875047 @default.
• W2155574915 hasRelatedWork W2339025832 @default.
• W2155574915 hasRelatedWork W2795180021 @default.
• W2155574915 hasRelatedWork W2887608266 @default.
• W2155574915 hasRelatedWork W2909399418 @default.
• W2155574915 hasRelatedWork W2944437644 @default.
• W2155574915 hasRelatedWork W3125223002 @default.
• W2155574915 hasRelatedWork W377899687 @default.
• W2155574915 hasVolume "33" @default.
• W2155574915 isParatext "false" @default.
• W2155574915 isRetracted "false" @default.
• W2155574915 magId "2155574915" @default.
• W2155574915 workType "article" @default.