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Dive into the research topics where Raquel Andres is active.

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Featured researches published by Raquel Andres.


Nature Genetics | 2007

Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.

Simon N. Stacey; Andrei Manolescu; Patrick Sulem; Thorunn Rafnar; Julius Gudmundsson; Sigurjon A. Gudjonsson; Gisli Masson; Margret Jakobsdottir; Steinunn Thorlacius; Agnar Helgason; Katja K. Aben; Luc J Strobbe; Marjo T Albers-Akkers; Dorine W. Swinkels; Brian E. Henderson; Laurence N. Kolonel; Loic Le Marchand; Esther Millastre; Raquel Andres; Javier Godino; María Dolores García-Prats; Eduardo Polo; Alejandro Tres; Magali Mouy; Jona Saemundsdottir; Valgerdur M. Backman; Larus J. Gudmundsson; Kristleifur Kristjansson; Jon Thor Bergthorsson; Jelena Kostic

Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: ∼25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor–positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5′ end of TNRC9 , a high mobility group chromatin–associated protein whose expression is implicated in breast cancer metastasis to bone.


Nature Genetics | 2009

Sequence variants at the TERT-CLPTM1L locus associate with many cancer types

Thorunn Rafnar; Patrick Sulem; Simon N. Stacey; Frank Geller; Julius Gudmundsson; Asgeir Sigurdsson; Margret Jakobsdottir; Hafdis T. Helgadottir; Steinunn Thorlacius; Katja K. Aben; Thorarinn Blondal; Thorgeir E. Thorgeirsson; Gudmar Thorleifsson; Kristleifur Kristjansson; Kristin Thorisdottir; Rafn Ragnarsson; Bardur Sigurgeirsson; Halla Skuladottir; Tomas Gudbjartsson; Helgi J. Ísaksson; Gudmundur V. Einarsson; Kristrun R. Benediktsdottir; Bjarni A. Agnarsson; Karl Olafsson; Anna Salvarsdottir; Hjordis Bjarnason; Margret Asgeirsdottir; Kari T. Kristinsson; Sigurborg Matthiasdottir; Steinunn G Sveinsdottir

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 × 10−12). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 × 10−8) and urinary bladder, prostate and cervix cancer (ORs = 1.07−1.31, all P < 4 × 10−4). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 × 10−4). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.


Nature Genetics | 2008

Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer.

Simon N. Stacey; Andrei Manolescu; Patrick Sulem; Steinunn Thorlacius; Sigurjon A. Gudjonsson; Gudbjorn F. Jonsson; Margret Jakobsdottir; Jon Thor Bergthorsson; Julius Gudmundsson; Katja K. Aben; Luc J Strobbe; Dorine W. Swinkels; K. C.Anton van Engelenburg; Brian E. Henderson; Laurence N. Kolonel; Loic Le Marchand; Esther Millastre; Raquel Andres; Berta Saez; Julio Lambea; Javier Godino; Eduardo Polo; Alejandro Tres; Simone Picelli; Johanna Rantala; Sara Margolin; Thorvaldur Jonsson; Helgi Sigurdsson; Thora Jonsdottir; Jón Hrafnkelsson

We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 × 10−12 for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer.


Nature Genetics | 2008

ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

Daniel F. Gudbjartsson; Patrick Sulem; Simon N. Stacey; Alisa M. Goldstein; Thorunn Rafnar; Bardur Sigurgeirsson; Kristrun R. Benediktsdottir; Kristin Thorisdottir; Rafn Ragnarsson; Steinunn G Sveinsdottir; Veronica Magnusson; Annika Lindblom; Konstantinos Kostulas; Rafael Botella-Estrada; Virtudes Soriano; Pablo Juberías; Matilde Grasa; Berta Saez; Raquel Andres; Dominique Scherer; Peter Rudnai; Eugene Gurzau; Kvetoslava Koppova; Lambertus A. Kiemeney; Margret Jakobsdottir; Stacy Steinberg; Agnar Helgason; Solveig Gretarsdottir; Margaret A. Tucker; Jose I. Mayordomo

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 × 10−9) and BCC (OR = 1.35, P = 1.2 × 10−6). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 × 10−7) and BCC (OR = 1.14, P = 6.1 × 10−4). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.3 × 10−4). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.


Journal of Clinical Oncology | 2011

Randomized Phase II Study Comparing Gemcitabine Plus Dacarbazine Versus Dacarbazine Alone in Patients With Previously Treated Soft Tissue Sarcoma: A Spanish Group for Research on Sarcomas Study

Xavier Garcia-del-Muro; Antonio Lopez-Pousa; Joan Maurel; Javier Martin; Javier Martinez-Trufero; Antonio Casado; Auxiliadora Gómez-España; Joaquin Fra; Josefina Cruz; Andres Poveda; Andrés Meana; Carlos Pericay; Ricardo Cubedo; J. Rubió; Ana De Juan; Nuria Lainez; Juan Antonio Carrasco; Raquel Andres; J. Buesa

PURPOSE To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. PATIENTS AND METHODS Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. RESULTS From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. CONCLUSION The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.


Journal of Clinical Oncology | 2009

Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas

Joan Maurel; Antonio Lopez-Pousa; Ramon De Las Penas; Joaquin Fra; Javier Martín; Josefina Cruz; Antonio Casado; Andres Poveda; Javier Martinez-Trufero; Carmen Balana; María Auxiliadora Gómez; R. Cubedo; O. Gallego; Belén Rubio-Viqueira; J. Rubió; Raquel Andres; Isabel Sevilla; Juan J. de la Cruz; Xavier Garcia del Muro; J. Buesa

PURPOSE To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. PATIENTS AND METHODS Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m(2) per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m(2) delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). RESULTS Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). CONCLUSION Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.


Anti-Cancer Drugs | 2012

Bevacizumab plus irinotecan in recurrent malignant glioma shows high overall survival in a multicenter retrospective pooled series of the Spanish Neuro-Oncology Research Group (GEINO).

Miguel J. Gil; Ramon De Las Penas; Gaspar Reynés; Carme Balañá; Pedro Pérez-Segura; Adelaida García-Velasco; Carlos Mesia; O. Gallego; Concepción Fernández-Chacón; M. Martinez-Garcia; Ana Herrero; Raquel Andres; Manuel Benavides; Teresa Quintanar; Xavier Pérez-Martin

There is no ‘standard of care’ for recurrent malignant glioma (MG). Our aim is to confirm the efficacy and safety of bevacizumab 10 mg/kg plus irinotecan 125 mg/m2 (or 340 mg/m2 if enzyme-inducing antiepileptic drugs) every 2 weeks for a maximum of 1 year in a retrospective pooled series of patients with recurrent MG. The inclusion criteria were as follows: age 18 years and above, histology of MG, progression after radiation and temozolomide, Karnofsky performance status (KPS) of at least 60, and signed informed consent for bevacizumab compassionate use. Response was assessed by MRI using the Macdonald criteria and evaluation of the FLAIR sequence every 8 weeks. A total of 130 patients were enrolled; 72% had glioblastoma (GBM). The median age of the patients was 53 years (20–78); the median KPS was 80%; the median number of prior chemotherapy lines was 2 (1–5); the median interval between the diagnosis of MG and inclusion was 14.6 months (2–166); and the median number of bevacizumab infusions was 8 (1–39). The median follow-up duration was 7.2 months (1–47). The median overall survival (OS) was 8.8 months for GBM and 11.2 months for anaplastic glioma (AG). The median progression-free survival was 5.1 months for GBM and 4.6 months for AG. The response rate was 56% for GBM and 68% for AG. Neurological and KPS improvements were observed in 49 and 45% of patients. Only KPS less than 80% was associated with a worse significant response rate (odds ratio, 0.57; 95% confidence interval, 0.22–0.96). The most frequent grades 3–4 toxicities were asthenia (7%), diarrhea (6%), and thromboembolic events (5%). There were five toxic deaths (4%). Bevacizumab plus irinotecan in recurrent MG improves responses, progression-free survival, and OS compared with historical data. KPS of at least 80% was a predictive factor for response and OS.


Journal of Clinical Oncology | 2013

Fluorouracil, Doxorubicin, and Cyclophosphamide (FAC) Versus FAC Followed by Weekly Paclitaxel As Adjuvant Therapy for High-Risk, Node-Negative Breast Cancer: Results From the GEICAM/2003-02 Study

Miguel Martín; Amparo Ruiz; Manuel Ruiz Borrego; Agustí Barnadas; Sonia L. González; Lourdes Calvo; Mireia Margeli Vila; Antonio Antón; Álvaro Rodríguez-Lescure; Miguel Angel Seguí-Palmer; Montserrat Munoz-Mateu; Joan Dorca Ribugent; José Manuel López-Vega; Carlos G. Jara; Enrique Espinosa; César Mendiola Fernández; Raquel Andres; Nuria Ribelles; Arrate Plazaola; Pedro Sánchez-Rovira; Javier Salvador Bofill; Carmen Crespo; Francisco Carabantes; Sonia Servitja; Jose Ignacio Chacon; César A. Rodríguez; Blanca Hernando; Isabel Alvarez; Eva Carrasco; Ana Lluch

PURPOSE Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established. PATIENTS AND METHODS Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival. RESULTS After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%). CONCLUSION For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.


Tumori | 2004

Prognostic value of serum S-100B in malignant melanoma.

Raquel Andres; Jose I. Mayordomo; Pedro Zaballos; Javier Rodino; Dolores Isla; P. Escudero; Luis Elosegui; Elena Filipovich; A. Sáenz; Eduardo Polo; Alejandro Tres

Aims and Background Although there is no established tumor marker of proven value for patients with melanoma, high serum levels of S-100B protein have been found in patients with melanoma and distant metastases. This study was performed to assess the prognostic value of this marker. Methods and Study Design Serum S-100B protein was measured by means of the LIA-mat System 300 (Sangtec S-100B LIA, AB Sangtec Medical, Bromma, Sweden) in 85 patients with melanoma. Results Mean serum S-100B protein was 0.075 μg/L (range, 0.001-0.470) in 66 patients with non-metastatic melanoma (stage I-III) versus 0.441 μg/L (range, 0.001-16.840) in 19 patients with metastatic melanoma (stage IV) (P <0.001, Mann Whitney U test). The median follow-up time was 329 days. Serum levels above 0.150 μg/L were found in 10 of patients with non-metastatic melanoma (15.2%) and in 17 of 19 patients with metastatic disease (89.4%). Median survival was 256 days for the 27 patients with serum S-100B levels above 0.150 μg/L versus 561 days for the 58 patients with normal values (P <0.3973). Conclusion Serum S-100B is a useful tumor marker in melanoma.


Journal of Clinical Oncology | 2015

Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study

Miguel Martín; Amparo Ruiz Simón; Manuel Ruiz Borrego; Nuria Ribelles; Álvaro Rodríguez-Lescure; Montserrat Munoz-Mateu; Sonia González; Mireia Margeli Vila; Agustí Barnadas; Manuel Ramos; Sonia del Barco Berrón; Carlos G. Jara; Lourdes Calvo; Noelia Martínez-Jañez; César Mendiola Fernández; César A. Rodríguez; Eduardo Martínez de Dueñas; Raquel Andres; Arrate Plazaola; Juan de la Haba-Rodriguez; José Manuel López-Vega; Encarna Adrover; Ana Isabel Ballesteros; Ana Santaballa; Pedro Sánchez-Rovira; José M. Baena-Cañada; Maribel Casas; María del Carmen Cámara; Eva Carrasco; Ana Lluch

PURPOSE Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC. PATIENTS AND METHODS Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m(2), respectively, × four cycles), followed by docetaxel (100 mg/m(2) × four cycles; EC-T) or epirubicin plus docetaxel (ET; 90 and 75 mg/m(2), respectively, × four cycles), followed by capecitabine (1,250 mg/m(2) twice a day on days 1 to 14, × four cycles; ET-X); all regimens were given every 3 weeks. The primary end point was invasive disease-free survival. Secondary end points included safety (with an alopecia-specific study) and overall survival (OS). RESULTS After a median follow-up of 6.6 years and 297 events, 86% of patients who received EC-T and 82% of those who received ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to 1.64; log-rank P = .03). The OS difference between arms was not statistically significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v 11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%); vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC-T wore wigs significantly longer than those who received ET-X (8.35 v 6.03 months). CONCLUSION Invasive disease-free survival, but not OS, was significantly superior for patients with node-positive early BC who received the adjuvant standard schedule EC-T than for those who received the experimental ET-X regimen. Toxicity profiles differed substantially across arms.

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Ana Lluch

University of Valencia

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P. Escudero

University of Zaragoza

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Antonio Lopez-Pousa

Autonomous University of Barcelona

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María José Escudero

Autonomous University of Barcelona

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