ORCID Profile
0000-0001-8296-5065
Current Organisations
Vall d´Hebron Institut d´Oncologia
,
Hospital Vall d'Hebron
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Publisher: Elsevier BV
Date: 11-2018
Publisher: American Association for Cancer Research (AACR)
Date: 02-2020
DOI: 10.1158/2159-8290.CD-19-0966
Abstract: HER2 mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer. This article is highlighted in the In This Issue feature, p. 161
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535389
Abstract: Comprehensive OncoPrint of nine patients with paired pre- and post-treatment tissue sequencing showing acquired alterations in the post-treatment tumor.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481759
Abstract: Table S5: Genes in the chr6q23-24 region, association with CN levels and pCR.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535398
Abstract: Supplementary data
Publisher: Impact Journals, LLC
Date: 17-04-2018
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2014
DOI: 10.1158/2159-8290.22535395
Abstract: PFS of (A) neratinib plus fulvestrant combination cohort and (B) neratinib monotherapy cohort. CI, confidence interval PFS, progression-free survival.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2018
DOI: 10.1038/NATURE25475
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535392.V1
Abstract: Overall sequencing CONSORT diagram. Flow diagram of study patients and analyzed biospecimens processed through and selected for central sequencing using MSK-IMPACT and Guardant360. cfDNA, cell-free DNA FFPE, formalin-fixed paraffin-embedded MSK-IMPACT, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets QC, quality control.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.DRUGPO.2016.07.004
Abstract: To date monitoring of cryptomarkets operating on the dark net has largely focused on market size and substance availability. Less is known of country specific differences in these indicators and how they may corroborate population prevalence estimates for substance use in different countries. All substance listings from the cryptomarket Agora were recorded over seven time points throughout February and March 2015. Agora was chosen due to its size as the second largest cryptomarket operating and the level of detail of information provided in in idual substance listings. Data were collated and the number of unique sellers selling each substance by country of origin was analysed. An average of 14,456.7 substance listings were identified across s led days from 868.7 unique sellers. The top five countries by number of listings were the USA, United Kingdom, Australia, China and the Netherlands, collectively accounting for 61.8% of all identified listings and 68% of all unique sellers. Australia was over represented in terms of sellers per capita, while China was over represented in new psychoactive substance (NPS) listings. When examined by number of listings per seller, the Netherlands and China stood out as particularly large, likely due to these countries' role in the local production of various illicit and new psychoactive substances. Numbers of sellers by country of origin appear to be influenced by several factors. Australia's overrepresentation in sellers per capita may indicate its relative geographical isolation and the potential for profit margins from selling online, while China's overrepresentation in NPS listings may reflect domestic production of these substances. Continued monitoring will provide enhanced understanding of the increasingly complex and globalised nature of illicit drug markets.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481762.V1
Abstract: Table S1: Clinicopathological characteristics of the patients. Table S2: List of 49 genes associated with CNAs in breast cancer from the COSMIC Cancer Gene Census database. Table S3: Gene ontology analysis of the genes correlated with the genome instability index. Table S4: Gene ontology analysis of the genes anti-correlated with the genome instability index.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535392
Abstract: Overall sequencing CONSORT diagram. Flow diagram of study patients and analyzed biospecimens processed through and selected for central sequencing using MSK-IMPACT and Guardant360. cfDNA, cell-free DNA FFPE, formalin-fixed paraffin-embedded MSK-IMPACT, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets QC, quality control.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481762
Abstract: Table S1: Clinicopathological characteristics of the patients. Table S2: List of 49 genes associated with CNAs in breast cancer from the COSMIC Cancer Gene Census database. Table S3: Gene ontology analysis of the genes correlated with the genome instability index. Table S4: Gene ontology analysis of the genes anti-correlated with the genome instability index.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535395.V1
Abstract: PFS of (A) neratinib plus fulvestrant combination cohort and (B) neratinib monotherapy cohort. CI, confidence interval PFS, progression-free survival.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535398.V1
Abstract: Supplementary data
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530768.V1
Abstract: AbstractPurpose: The heterogeneity of response to anti-HER2 agents represents a major challenge in patients with HER2-positive breast cancer. To better understand the sensitivity and resistance to trastuzumab and lapatinib, we investigated the role of copy number aberrations (CNA) in predicting pathologic complete response (pCR) and survival outcomes in the NeoALTTO trial. Experimental Design: The neoadjuvant phase III NeoALTTO trial enrolled 455 patients with HER2-positive early-stage breast cancer. DNA s les from 269 patients were assessed for genome-wide copy number profiling. Recurrent CNAs were found with GISTIC2.0. Results: CNA estimates were obtained for 184 patients included in NeoALTTO. Among those, matched transcriptome and whole-exome data were available for 154 and 181 patients, respectively. A significant association between gene copy number and pCR was demonstrated for i ERBB2 /i lification. Nevertheless, i ERBB2 /i lification ceased to be predictive once i ERBB2 /i expression level was considered. GISTIC2.0 analysis revealed 159 recurrent CNA regions. Lower copy number levels of the 6q23-24 locus predicted absence of pCR in the whole cohort and in the estrogen receptor–positive subgroup. 6q23-24 deletion was significantly more frequent in i TP53 /i wild-type (WT) compared with i TP53 /i -mutated, resulting in copy number levels significantly associated with lack of pCR only in the i TP53 /i WT subgroup. Interestingly, a gene-ontology analysis highlighted several immune processes correlated to 6q23-24 copy number. Conclusions: Our analysis identified i ERBB2 /i copy number as well as 6q23-24 CNAs as predictors of response to anti–HER2-based treatment. i ERBB2 /i expression outperformed i ERBB2 /i lification. The complexity of the 6q23-24 region warrants further investigation. /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6547849.V1
Abstract: Abstract i HER2 /i mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with i HER2 /i -mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER sup + /sup patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating i HER2 /i or i HER3 /i alterations were associated with poor treatment outcome. Similarly, acquisition of multiple i HER2 /i -activating events, as well as gatekeeper alterations, were observed at disease progression in a high proportion of patients deriving clinical benefit from neratinib. Collectively, these data define i HER2 /i mutations as a therapeutic target in breast cancer and suggest that coexistence of additional HER signaling alterations may promote both i de novo /i and acquired resistance to neratinib. Significance: i HER2 /i mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer. i This article is highlighted in the In This Issue feature, p. 161 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 28-07-2021
DOI: 10.1158/1078-0432.CCR-21-1317
Abstract: The heterogeneity of response to anti-HER2 agents represents a major challenge in patients with HER2-positive breast cancer. To better understand the sensitivity and resistance to trastuzumab and lapatinib, we investigated the role of copy number aberrations (CNA) in predicting pathologic complete response (pCR) and survival outcomes in the NeoALTTO trial. The neoadjuvant phase III NeoALTTO trial enrolled 455 patients with HER2-positive early-stage breast cancer. DNA s les from 269 patients were assessed for genome-wide copy number profiling. Recurrent CNAs were found with GISTIC2.0. CNA estimates were obtained for 184 patients included in NeoALTTO. Among those, matched transcriptome and whole-exome data were available for 154 and 181 patients, respectively. A significant association between gene copy number and pCR was demonstrated for ERBB2 lification. Nevertheless, ERBB2 lification ceased to be predictive once ERBB2 expression level was considered. GISTIC2.0 analysis revealed 159 recurrent CNA regions. Lower copy number levels of the 6q23-24 locus predicted absence of pCR in the whole cohort and in the estrogen receptor–positive subgroup. 6q23-24 deletion was significantly more frequent in TP53 wild-type (WT) compared with TP53-mutated, resulting in copy number levels significantly associated with lack of pCR only in the TP53 WT subgroup. Interestingly, a gene-ontology analysis highlighted several immune processes correlated to 6q23-24 copy number. Our analysis identified ERBB2 copy number as well as 6q23-24 CNAs as predictors of response to anti–HER2-based treatment. ERBB2 expression outperformed ERBB2 lification. The complexity of the 6q23-24 region warrants further investigation.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530768
Abstract: AbstractPurpose: The heterogeneity of response to anti-HER2 agents represents a major challenge in patients with HER2-positive breast cancer. To better understand the sensitivity and resistance to trastuzumab and lapatinib, we investigated the role of copy number aberrations (CNA) in predicting pathologic complete response (pCR) and survival outcomes in the NeoALTTO trial. Experimental Design: The neoadjuvant phase III NeoALTTO trial enrolled 455 patients with HER2-positive early-stage breast cancer. DNA s les from 269 patients were assessed for genome-wide copy number profiling. Recurrent CNAs were found with GISTIC2.0. Results: CNA estimates were obtained for 184 patients included in NeoALTTO. Among those, matched transcriptome and whole-exome data were available for 154 and 181 patients, respectively. A significant association between gene copy number and pCR was demonstrated for i ERBB2 /i lification. Nevertheless, i ERBB2 /i lification ceased to be predictive once i ERBB2 /i expression level was considered. GISTIC2.0 analysis revealed 159 recurrent CNA regions. Lower copy number levels of the 6q23-24 locus predicted absence of pCR in the whole cohort and in the estrogen receptor–positive subgroup. 6q23-24 deletion was significantly more frequent in i TP53 /i wild-type (WT) compared with i TP53 /i -mutated, resulting in copy number levels significantly associated with lack of pCR only in the i TP53 /i WT subgroup. Interestingly, a gene-ontology analysis highlighted several immune processes correlated to 6q23-24 copy number. Conclusions: Our analysis identified i ERBB2 /i copy number as well as 6q23-24 CNAs as predictors of response to anti–HER2-based treatment. i ERBB2 /i expression outperformed i ERBB2 /i lification. The complexity of the 6q23-24 region warrants further investigation. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22481759.V1
Abstract: Table S5: Genes in the chr6q23-24 region, association with CN levels and pCR.
Publisher: Oxford University Press (OUP)
Date: 31-03-2021
DOI: 10.1093/JNCI/DJAB057
Abstract: In early-stage HER2-positive breast cancer, biomarkers that guide deescalation and/or escalation of systemic therapy are needed. CelTIL score is a novel, combined biomarker based on stromal tumor-infiltrating lymphocytes and tumor cellularity and is determined in tumor biopsies at week 2 of anti-HER2 therapy only. We evaluated the prognostic value of CelTIL in 196 patients with early-stage HER2-positive disease treated with standard trastuzumab-based chemotherapy in the NeoALTTO phase III trial. Using a prespecified CelTIL cutoff, a better 5-year event-free survival and overall survival was observed between CelTIL-high and CelTIL-low score with a 76.4% (95% confidence interval [CI] = 68.0% to 85.0%) vs 59.7% (95% CI = 50.0% to 72.0%) (hazard ratio = 0.40, 95% CI = 0.17 to 0.94) and 86.4% (95% CI = 80.0% to 94.0%) vs 73.5% (95% CI = 64.0% to 84.0%) (hazard ratio = 0.43, 95% CI = 0.20 to 0.92), respectively. Statistical significance was maintained after adjusting for baseline tumor-infiltrating lymphocytes, hormone receptor status, pretreatment tumor size and nodal status, type of surgery, treatment arm, and pathological complete response. Further studies to support CelTIL as an early readout biomarker to help deescalate or escalate systemic therapy in HER2-positive breast cancer seem warranted.
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22535389.V1
Abstract: Comprehensive OncoPrint of nine patients with paired pre- and post-treatment tissue sequencing showing acquired alterations in the post-treatment tumor.
Publisher: Elsevier BV
Date: 09-2014
Location: Spain
No related grants have been discovered for Cristina Saura Manich.