Alba E.,Hospital Universitario Virgen Of La Victoria |
De la Haba J.R.,Hospital Reina Sofia |
Arcusa Lanza A.,Consorci Sanitari de Terrassa |
Chacon J.I.,H Virgen de la Salud |
And 5 more authors.
Annals of Oncology | Year: 2012
Background: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. Patients and Methods: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m. 2 plus cyclophosphamide 600 mg/m. 2 × 4 cycles followed by docetaxel 100 mg/m. 2× 4 cycles [EC-T]) or HT (exemestane 25 mg daily × 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. Results: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. Conclusions: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Acera A.,Bioftalmik SL |
Ignacio R.-A.,ICQO |
Vega S.C.,Bioftalmik SL |
Rezola R.,Onkologikoa |
And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013
PURPOSE. To investigate the effect of poly (lactic-co-glycolic acid) (PLGA) implants loaded with mitomycin C (MMC) and with different adjuvant treatments after glaucoma filtration surgery (GFS), in comparison to standard treatments. METHODS. Forty-two New Zealand White rabbits underwent bilateral GFS and received different treatments: topical MMC (group 1); topical 5-fluorouracil (5-FU; group 2); PLGA implant (group 3); MMC-loaded and -coated PLGA implant (group 4); MMC-loaded and 5-FU- coated PLGA implant (group 5); subconjunctival bevacizumab (group 6); MMC-loaded PLGA implant and subconjunctival bevacizumab (group 7); and no treatment (right eye of all animals; control group). Intraocular pressure (IOP) and filtering bleb were evaluated on different days after GFS. Histology was performed to examine the conjunctiva, sclerotomy, filtering bleb, and persistence of the implant. RESULTS. The best hypotensive results were achieved in the MMC-loaded and -coated PLGA implant group, which presented the lowest IOP values on days 1, 5, 7, 14, and 28 after GFS. Excluding the implant groups, in which the bleb could not be properly measured, bleb survival was superior to controls in groups 1, 2 and lower in group 6. Group 7 presented greater extension, height, and vascularization of the bleb. Epithelial thinning and lymphoplasmacytic infiltrate were observed in groups 1, 2, 4, 5, and 7. The rates of closure of the sclerotomy and bleb were 100% and 76%, respectively, and implant persistence was 95%. CONCLUSIONS. MMC-loaded and -coated implants have optimal surgical results, followed by topical MMC application. In this experimental model, bevacizumab could interact with MMC. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
PubMed | Parc Tauli Health Corporation, Reina Sofia Hospital Complex, University of Barcelona, Valencian Institute of Oncology and 13 more.
Type: Journal Article | Journal: The oncologist | Year: 2016
In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.
PubMed | Institute Of Recerca Hospital Del Mar Imim, Hospital Universitario Virgen Of Las Nieves, University of Granada, Hospital Universitario Of Gran Canaria Dr Negrin and 7 more.
Type: Journal Article | Journal: Prostate cancer and prostatic diseases | Year: 2016
Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients.A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator.(XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and DAmico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing DAmico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002).We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.
PubMed | University of Otago, Virgen Of La Salud Hospital, Complejo Hospitalario Of Jaen, Institute of Health Research INCLIVA and 16 more.
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016
Hormone receptor-positive (HR+) breast cancer is clinically and biologically heterogeneous and subgroups with different prognostic and treatment sensitivities need to be identified.Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR+/HER2- disease randomized to neoadjuvant multi-agent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based Chemo-Endocrine Score (CES). CESs predictive ability was evaluated in 4 independent neoadjuvant datasets (n=675) and 4 adjuvant datasets (n=1,505). The association of CES, intrinsic biology and PAM50 risk of relapse (ROR) was explored across 6,007 tumors.Genes associated with endocrine sensitivity were also found associated with chemotherapy resistance. In the chemotherapy test/validation datasets, CES was independently associated with pathological complete response, even after adjusting for intrinsic subtype. pCR rates of the CES endocrine sensitive (CES-E), uncertain (CES-U) and chemotherapy sensitive (CES-C) groups in both datasets combined were 25%, 11% and 2%, respectively. In the endocrine test/validation datasets, CES was independently associated with response. Compared to ROR, >90% of ROR-low and ROR-high tumors were identified as CES-E and CES-C, respectively; however, each CES-group represented >25% of ROR-intermediate disease. In terms of survival outcome, CES-C was associated with poor relapse-free survival in patients with ROR-intermediate disease treated with adjuvant endocrine therapy-only or no adjuvant systemic therapy, but not in patients treated with (neo)adjuvant chemotherapy.CES is a genomic signature capable of estimating chemo-endocrine sensitivity in HR+ breast cancer beyond intrinsic subtype and risk of relapse.
Anton A.,Hospital Universitario Miguel Servet |
Ruiz A.,Instituto Valenciano Of Oncologia |
Plazaola A.,Onkologikoa |
Calvo L.,Complejo Hospitalario Universitario Of runa |
And 11 more authors.
Annals of Oncology | Year: 2011
Background: We previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial. Patients and methods: Patients were treated with LD 50 mg/m2 and docetaxel 60 mg/m2 every 21days associated with standard trastuzumab dose and pegfilgrastim support. Results: Fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed. Conclusions: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Ruiz-Martinez J.,Donostia Hospital |
Ruiz-Martinez J.,CIBER ISCIII |
Gorostidi A.,Donostia Hospital |
Goyenechea E.,Donostia Hospital |
And 7 more authors.
Movement Disorders | Year: 2011
It has been proposed that olfactory tests and metaiodobenzylguanidine cardiac scintigraphy may help diagnose idiopathic Parkinson's disease in the premotor phase. However, it is not clear what value these tests have in all patients with Parkinson's disease and, particularly, in those who carry mutations in LRRK2. The objective was to analyze olfactory dysfunction and the changes in cardiac I-metaiodobenzylguanidine uptake in patients with Parkinson's disease carrying the R1441G and G2019S mutations in LRRK2, and in patients with Parkinson's disease with no known mutations. Patients with Parkinson's disease were screened for R1441G and G2019S LRRK2 gene mutations and classified as LRRK2 mutation carriers or noncarriers. A total of 190 patients with Parkinson's disease (44 LRRK2 mutation carriers) were tested for olfactory dysfunction using the Brief Smell Identification Test. Cardiac 123I-metaiodobenzylguanidine scintigraphy was performed on 90 patients with Parkinson's disease (27 LRRK2 mutation carriers). Thirty-six percent of patients with LRRK2 mutations have hyposmia, compared to 75% of noncarrier patients with Parkinson's disease (P <.001). Sixty-six percent of LRRK2 mutation carriers have low early metaiodobenzylguanidine uptake, compared to 86% of noncarriers (P =.048). Similarly, the heart/mediastinum ratio in delayed metaiodobenzylguanidine images appeared to differ between these groups of patients with Parkinson's disease, although these results did not reach statistical significance. The data obtained indicate that olfactory and cardiac impairment is less prevalent when Parkinson's disease is associated with mutations in LRRK2, although the underlying mechanisms for this difference remain unclear. Thus, such screening would be less useful to detect the premotor phase in asymptomatic relatives who carry mutations in LRRK2 than in cases not associated with LRRK2. © 2011 Movement Disorder Society.
Bernet L.,Hospital Lluis Alcanyis |
Urruticoechea A.,Onkologikoa |
Vicente F.,Complejo Hospitalario Of Navarra
Revista de Senologia y Patologia Mamaria | Year: 2014
Objectives The importance of obtaining free margins in breast-conserving surgery is well known. However, there are no uniform criteria on when to perform a reexcision. Therefore, the Breast Study Group decided to identify current practice in Spain through a survey. Materials and method An online survey was developed consisting of 28 items divided into the following 4 data sections: General information, perioperative information and decisions, postoperative information and decisions, and other factors. Questionnaires were sent to 87 centers, and responses were obtained from 55 (63.2%). Results Margins were always examined intraoperatively in 60% of the centers and occasionally in 22%. Close margins were defined as those 1 mm away from the margin by 58% of participants. Most centers opted for reexcision when information on involved margins or close margins was obtained intraoperatively. If the information was obtained postoperatively, reexcision was performed in 70-100% of cases of involved margins but in only 18-29% of cases of close margins. In cases of involved margins without reexcision, 50% of respondents increased the radiation dose. Conclusion In Spain, reexcision is usually performed in cases of involved margins. However, there is an appreciable variation in this decision in cases of close margins. © 2014 SESPM. Published by Elsevier España, S.L. All rights reserved.
PubMed | Hospital Universitario La Paz, Hospital Clinico Of Salamanca, Hospital Universitario Marques Of Valdecilla, Hospital Xeral Cies Of Vigo and 8 more.
Type: Journal Article | Journal: Breast care (Basel, Switzerland) | Year: 2016
The aim of this project was to provide an expert opinion regarding anti-human epidermal growth factor receptor 2 (HER2) therapy beyond second-line treatment of metastatic breast cancer (mBC).A group of experts discussed specific issues concerning anti-HER2 therapy in late-line settings in mBC.Trastuzumab emtansine (T-DM1) or dual HER2 blockade appeared to be good options for HER2-positive mBC after 2 HER2-targeted therapies. Once an objective response has been achieved with anti-HER2-containing therapy, the anti-HER2 agent can be continued until progression of the disease, unacceptable toxicity or patient decision. mBC treated with 3 consecutive lines of anti-HER therapy, 1 being a dual HER2 blockade and with early progression of disease during a fourth or later-line treatment, are clinically resistant to anti-HER therapy. For progression of metastasis in the brain after anti-HER2 therapy, lapatinib and chemotherapy appear to be a good alternative after best local treatment.Further clinical trials are needed to provide valuable knowledge about the best treatment options in the later settings of mBC.
Leis O.,Regulation of Cell Growth Laboratory |
Eguiara A.,Regulation of Cell Growth Laboratory |
Lopez-Arribillaga E.,Regulation of Cell Growth Laboratory |
Alberdi M.J.,Onkologikoa |
And 5 more authors.
Oncogene | Year: 2012
The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires self-renewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation. © 2012 Macmillan Publishers Limited All rights reserved.