A Arcusa

Consorci Sanitari de Terrassa, Terrassa, Catalonia, Spain

Are you A Arcusa?

Claim your profile

Publications (38)209.46 Total impact

  • Cancer Research 05/2015; 75(9 Supplement):P6-08-10-P6-08-10. DOI:10.1158/1538-7445.SABCS14-P6-08-10 · 9.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-, post-, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor-positive, human epidermal growth hormone factor negative, and node-negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p < 0.05). Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients' anxiety about the selected adjuvant therapy decreased with use of the GEP.
    Current Medical Research and Opinion 04/2015; 31(6):1-28. DOI:10.1185/03007995.2015.1037730 · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To analyze BRCA1 and BRCA2 genes using a cost-effective and rapid approach based on next generation sequencing (NGS) technology. A population of Spanish cancer patients with a personal or familial history of breast and/or ovarian cancer was analyzed for germline mutations in BRCA1 and BRCA2 genes. The methodology relies on a 5 multiplex PCR assay coupled to NGS. Ten pathogenic mutations (four in BRCA1 and six in BRCA2 gene) were identified in a Spanish population. The deletion c.1792delA, in exon 10, and the duplication c.5869dupA, in exon 11 of BRCA2 gene were not previously reported and should be considered as pathogenic due to its frameshift nature. Two novel frameshift mutations in BRCA2 gene were detected using the multiplex PCR-based assay following by NGS.
    Clinical and Translational Oncology 01/2015; DOI:10.1007/s12094-014-1271-x · 1.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC).Methods:Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated.Results:Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival.Conclusions:The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.British Journal of Cancer advance online publication 7 August 2014; doi:10.1038/bjc.2014.444 www.bjcancer.com.
    British Journal of Cancer 08/2014; DOI:10.1038/bjc.2014.444 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim The aim of the present study was to analyze the age of breast cancer patients managed with curative approach at the time of treatment with radiotherapy. Background Breast cancer is the most frequent neoplasm in women. Little is known with regard to the age of patients at diagnosis, and some authors have suggested that breast cancer is now affecting women who are younger than before. Materials and methods We performed a descriptive study of our series of breast cancer patients from 1998 to 2011. The age of patients, city of residence, year of treatment and uni- or bilateral location were extracted from the administrative database of the Radiation Oncology Department. The demographical and reference populational data were extracted from the Catalan Institute of Statistics. Results 3382 patients were obtained. The mean age was 57.79 years. No statistical differences were observed in the mean age during the period of study (p > 0.05), nor in patients with bilateral neoplasias with regard to unilateral tumours (p > 0.5). Patients aged less than 30, 40, 50 and 65 years were 0.3%, 6.3%, 27.0% and 69.1%, respectively. The proportion of patients aged less, equal or more than 40 and 50 years was not statistically different. Conclusions Breast cancer patients treated with adjuvant radiotherapy after radical surgery have not experienced significant changes in their mean age at treatment. The subgroups of patients that remain out of the mammographic screening programmes were unchanged as well. The observed differences can be explained by demographical disparities and by a probable increase in the indications for adjuvant radiotherapy.
    Reports of Practical Oncology and Radiotherapy 07/2014; DOI:10.1016/j.rpor.2014.05.003
  • 01/2014; 10(2-3). DOI:10.5209/rev_PSIC.2013.v10.n2-3.43448
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Energy restriction from a low-calorie diet and increased energy expenditure induced by physical activity (PA) could promote weight loss/maintenance and be important determinants of breast cancer (BC) prognosis. The aim of this study was to assess participation and adherence of overweight and obese BC survivors to a lifestyle intervention and to demonstrate the capacity of this intervention to induce weight loss and nutritional changes. This single-arm pre-post study, which involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi-weekly PA sessions of moderate-to-high intensity led by PA monitors, was offered to overweight and obese BC survivors shortly after treatment. Before and after the intervention, anthropometry, dietary information, quality of life (QoL) and cardiorespiratory fitness (CRF) were collected. A total of 112 BC survivors were invited to participate: 42 of them started the intervention and 37 completed it. Participants attended more than 90 % of the sessions offered and showed a significant weight loss of 5.6 ± 2.0 kg, as well as significant decreases in body mass index, fat mass and waist circumference. Significant decreases in total energy (-25 %), fat (-35 %), saturated fat (-37 %) and carbohydrate (-21 %) intakes were observed while QoL and CRF showed significant increases. This feasibility study demonstrated the success of a short-term diet and PA intervention to induce weight loss and promote healthful changes in BC survivors. Assessing the long-term effects of these changes, and in particular their possible impact of BC prognosis, and designing interventions reaching a wider number of BC survivors are still issues to be addressed.
    Medical Oncology 01/2014; 31(1):783. DOI:10.1007/s12032-013-0783-5 · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.
    Clinical and Translational Oncology 08/2013; DOI:10.1007/s12094-013-1070-9 · 1.60 Impact Factor
  • 01/2013; 9(2-3). DOI:10.5209/rev_PSIC.2013.v9.n2-3.40898
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims:To compare different methods in order to assess adherence and persistence with oral endocrine therapy in women diagnosed with breast cancer (BC) in Catalonia.Materials and methods:This study covered all women newly diagnosed with stage I, II or IIIa BC and positive hormone receptors at six hospitals in Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician report and patient self-report using a telephone questionnaire. Persistence was measured by refill prescriptions. We used the Kappa index to compare adherence measures and logistic regression to evaluate adherence-related risk factors.Results:The study covered a total of 692 women. Adherence ranged from 92% (self-report) to 94.7% (physician report), depending on the measure used; persistence was 74.7% at 5 years of follow-up. Low concordance between measures was observed (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence than those aged <50 years. Adherence was also associated with: adjuvant chemotherapy and sequential hormonal therapy.Conclusions:Concordance between the different measures was remarkably low, indicating the need for further research. Adherence is an issue in the management of BC patients taking oral drugs, and should be assessed in clinical practice.
    British Journal of Cancer 09/2012; 107(8):1249-56. DOI:10.1038/bjc.2012.389 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the impact of adapted ice cream as a dietary supplement on the quality of life (QLQ) of malnourished patients with cancer. We present an exploratory prospective observational study comparing two patterns of nutrition in cancer patients admitted during the study period who presented malnutrition disorders: adapted ice cream (Group I: 39 patients) and nutritional supplements (Group II: 31 patients). Patients were selected from two different hospitals from the same Oncologic Institute. QLQ was evaluated with the Hospital Anxiety and Depression Scale (HADS) and QLQ of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30). Nutrition was determined by the PG-SGA test. HADS showed significant differences in anxiety (p = 0.023) and depression (p = 0.011) at the end of the study only in Group I. QLQ-C30 revealed statistically significant differences in baseline measures of global dimension between the two groups (Group I: 40.64-56.36 CI; Group II: 25.70-43.11 CI; p = 0.017). Differences were also present in the social dimension (Group I: 77.42-93.51 CI; Group II: 55.85-82.85 CI; p = 0.039). Statistically significant differences were observed between the two groups at the end of the study in the global scale: Group I had 49.36-63.88 CI and Group II had 33.05-51.88 CI (p = 0.016), and in the fatigue scale: Group I had 36.19-53.83 CI and Group II had mean = 65.87, 52.50-79.23 CI (p = 0.007). The administration of ice cream could cover, in part, the social aspect of food and improve QLQ in malnourished cancer patients. These results are encouraging and deserve further confirmation.
    Clinical and Translational Oncology 01/2012; 14(1):66-72. DOI:10.1007/s12094-012-0763-9 · 1.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with life-threatening toxicity following exposure to the fluoropyrimidine drugs 5-fluorouracil (5-FU) and capecitabine (CAP), widely used for the treatment of colorectal cancer and other solid tumors. The most prominent loss-of-function allele of the DPYD gene is the splice-site mutation c.1905+1G>A. In this study we report the case of a 73-year old woman with metastatic colorectal cancer who died from drug-induced toxicity after the first cycle of 5-FU-containing chemotherapy. Her symptoms included severe neutropenia, thrombocytopenia, mucositis and diarrhea; she died 16 days later despite intensive care measures. Post-mortem genetic analysis revealed that the patient was homozygous for the c.1905+1G>A deleterious allele and several family members consented to being screened for this mutation. This is the first report in Spain of a case of 5-FU-induced lethal toxicity associated with a genetic defect that results in the complete loss of the DPD enzyme. Although the frequency of c.1905+1G>A carriers in the white population ranges between 1 and 2%, the few data available for the Spanish population and the severity of this case prompted us to design a genotyping procedure to prevent future toxic effects of 5-FU/CAP. Since our group had previously developed a high-resolution melting (HRM) assay for the simultaneous detection of KRAS, BRAF, and/or EGFR somatic mutations in colorectal and lung cancer patients considered for EGFR-targeted therapies, we included the DPYD c.1905+1G>A mutation in the screening test that we describe herein. HRM provides a rapid, sensitive, and inexpensive method that can be easily implemented in diagnostic settings for the routine pre-therapeutic testing of a gene mutation panel with implications in the pharmacologic treatment.
    Frontiers in Genetics 01/2012; 3:312. DOI:10.3389/fgene.2012.00312
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.
    BMC Cancer 09/2011; 11:406. DOI:10.1186/1471-2407-11-406 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined. We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity. At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided. As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).
    New England Journal of Medicine 12/2010; 363(23):2200-10. DOI:10.1056/NEJMoa0910320 · 54.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a novel complex mutation that consists of a deletion of 12 bp and an insertion of 2 bp (c.8402_8413del12ins2bp) in the exon 18 of the BRCA2 gene. This is a frameshift mutation that causes a disruption of the translational reading frame resulting in a stop codon downstream in the 2729 position of the BRCA2 protein. The mutation was present in a Spanish hereditary male/female breast cancer family.
    Breast Cancer Research and Treatment 03/2010; 123(2):587-90. DOI:10.1007/s10549-010-0830-2 · 4.20 Impact Factor
  • Critical Reviews in Oncology/Hematology 10/2009; 72(1). DOI:10.1016/S1040-8428(09)70045-9 · 4.05 Impact Factor
  • Cancer Research 02/2009; 69(2 Supplement):5117-0. DOI:10.1158/0008-5472.SABCS-5117 · 9.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy of exemestane as neoadjuvant treatment, 55 postmenopausal women (mean age: 76 years; range: 66-86) with oestrogen-positive non-metastatic breast tumour and ineligible for conservative surgery were recruited into this phase II trial to receive oral exemestane (25 mg day(-1)) for 6 months. Tumour response was evaluated by clinical examination, mammography and breast ultrasound every 2 months (RECIST criteria). Overall clinical response to treatment was observed in 33/54 patients (61.1%; 95% CI: 48.1-74.0). Radiological responses in 45 evaluable patients were partial response in 23, stable disease in 21 and disease progression in one. Median time to surgery from the commencement of treatment was 7 months; conservative surgery in 24 patients (55.8%) and mastectomy in 19 patients (34.5%); no surgery (patient choice or considered not suitable by attending physician) in 12 patients. Pathologic complete response was observed in breast and axilla in one patient (2.3%) and different forms of persistent disease in 23 (53.5%) patients. Treatment tolerance was good. No patient withdrew from the study because of toxic events. We conclude that exemestane as a primary treatment is feasible and very active in elderly patients with large-sized breast cancer tumour. Conservative surgery is feasible in responding patients. No severe adverse events were detected. The optimal hormonal treatment schedule remains to be determined.
    British Journal of Cancer 02/2009; 100(3):442-9. DOI:10.1038/sj.bjc.6604868 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In clinical practice, it is possible to classify breast tumors according to estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression: ER negative, PgR negative, and HER2 overexpressing; ER negative, PgR negative, and HER2 negative; ER positive, PgR positive, and HER2 negative; ER positive, PgR positive, and HER2 overexpressing; and the less frequent remaining 4 combinations. The aim of this study was to determine the percentage of pathologic complete response (pCR) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant or primary chemotherapy with anthracyclines and taxanes grouped according to ER, PgR, and HER2 status. Patients with LABC treated with primary chemotherapy including anthracyclines and taxanes were grouped according to ER, PgR, and HER2 status; pCR rates were analyzed using the chi(2) test; and correlations with a P value of < or = 0.05 were considered statistically significant. A total of 103 patients were treated. Only 100 patients were included for the analysis of pCR. Eighteen patients exhibited pCR. The pCR rate for each subgroup was as follows: 39.1% (9 of 23) had ER-negative, PgR-negative, and HER2-negative disease (P < 0.01); 35.7% (5 of 14) had ER-negative, PgR-negative, and HER2-overexpressing disease; 33.3% (3 of 9) had ER-positive, PgR-positive, and HER2-overexpressing disease; and 2.8% (1 of 36) had ER-positive, PgR-positive, and HER2-negative disease (P < 0.01). In patients with LABC, grouping breast tumors according to ER, PgR, and HER2 status can help predict pCR to primary chemotherapy.
    Clinical Breast Cancer 04/2007; 7(7):559-64. DOI:10.3816/CBC.2007.n.012 · 2.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to analyse the toxicity and health related quality of life (HRQoL) of breast cancer patients treated with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) and TAC (docetaxel, doxorubicin, cyclophosphamide) with and without primary prophylactic G-CSF (PPG). This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients. After the entry of the first 237 patients, the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia. A total of 1047 evaluable patients from 49 centres in Spain, two in Poland and four in Germany were included in the trial. Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 questionnaires were compared in the three groups (FAC, TAC pre-amendment and TAC post-amendment). The addition of PPG to TAC significantly reduced the incidence of neutropenic fever, grade 2-4 anaemia, asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia. Patient QoL decreased during chemotherapy, more with TAC than FAC, but returned to baseline values afterwards. The addition of PPG to TAC significantly reduced the percentage of patients with clinically relevant Global Health Status deterioration (10 or more points over baseline value) at the end of chemotherapy (64% versus 46%, P<0.03). The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.
    Annals of Oncology 08/2006; 17(8):1205-12. DOI:10.1093/annonc/mdl135 · 6.58 Impact Factor

Publication Stats

634 Citations
209.46 Total Impact Points

Institutions

  • 2005–2014
    • Consorci Sanitari de Terrassa
      Terrassa, Catalonia, Spain
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 2004–2012
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
    • Eli Lilly
      Indianapolis, Indiana, United States