Yolanda Fernández

Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain

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Publications (40)104.51 Total impact

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    ABSTRACT: The increase in life expectancy in the western world means that we are faced with patients diagnosed with breast cancer in old age with increasing frequency. The management of these cases is a challenge for the oncologist, who must take into account the conditions associated with advanced age and the lack of trials in this population. In this review, we addressed the incorporation of geriatric assessment methods that may be useful in making decisions, the particular biological characteristics of breast cancer in elderly patients and their treatment in both localized and advanced disease. Finally, we collected recommendations based on scientific evidence regarding the monitoring and life-style after finishing treatment.
    Clinical and Translational Oncology 10/2013; · 1.28 Impact Factor
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    ABSTRACT: BACKGROUND: The prevalence of BRCA1 and BRCA2 mutations in Spain is heterogeneous and varies according to geographical origin of studied families. The contribution of these mutations to hereditary breast and ovarian cancer has not been previously investigated in Asturian populations (Northern Spain). METHODS: In the present work, 256 unrelated high-risk probands with breast and/or ovarian cancer from families living in Asturias were analyzed for the presence of a BRCA1 or BRCA2 gene mutation from October 2007 to May 2012. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened both by direct sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: A total of 59 families (23%) were found to carry a pathogenic germ line mutation, 39 in BRCA1 and 20 in BRCA2. Twenty nine additional families (12%) carried an unknown significance variant. We detected 28 distinct pathogenic mutations (16 in BRCA1 and 12 in BRCA2), of which 3 mutations in BRCA1 (c.1674delA, c.1965C>A and c.2900_2901dupCT) and 5 in BRCA2 (c.262_263delCT, c.2095C>T, c.3263dupC, c.4030_4035delinsC, c.8042_8043delCA) had not been previously described.The novel mutations c.2900_2901dupCT in BRCA1 and c.4030_4035delinsC in BRCA2 occurred in 8 and 6 families respectively and clustered in two separated small geographically isolated areas suggesting a founder effect. These 2 mutations, together with the Galician BRCA1 mutation c.211A>G (9 families), and the common BRCA1 mutation c.3331_3334delCAAG (6 families), account for approximately 50% of all affected families. By contrast, very frequent mutations in other Spanish series such as the BRCA1 Ashkenazi founder mutation c.68_69delAG, was found in only one family. CONCLUSIONS: In this study we report the BRCA1 and BRCA2 spectrum of mutations and their geographical distribution in Asturias, which largely differ from other areas of Spain. Our findings may help design a first step recurrent mutation panel for screening high-risk breast and/or ovarian cancer families from this specific area.
    BMC Cancer 05/2013; 13(1):243. · 3.33 Impact Factor
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    ABSTRACT: Fulvestrant is a selective estrogen receptor downregulator, behaving as a complete antagonist. It was initially approved, at a dose of 250mg, to treat hormone dependant breast cancer in second line setting. However, a series of pharmacological and pre-clinical studies have suggested that a higher dose of 500mg may be more effective. The present work summarizes and discusses clinical trials that have aimed to test the benefits of administering fulvestrant at a higher dose. The data support the use of a higher, and more possibly, effective dose of the agent.
    Cancer Treatment Reviews 07/2012; · 6.02 Impact Factor
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    ABSTRACT: Pegylated liposomal doxorubicin (PLD) is currently the reference treatment for platinum-resistant ovarian cancer. The combination of PLD and gemcitabine and the administration of gemcitabine at a fixed dose rate infusion (FDRI) seem to have additive activity in this disease setting. We have launched a phase Ib study with the combination of FDRI gemcitabine followed by PLD in recurrent ovarian cancer with a platinum-free interval of less than 1 year, with parallel pharmacokinetic and pharmacogenetic studies. The starting dose of gemcitabine was 1500 mg/m², 10 mg/m² per minute, every 2 weeks (± 250 mg gemcitabine titration depending on toxicity), followed by PLD 35 mg/m² every 4 weeks. Gemcitabine pharmacokinetics and equilibrative nucleoside transporter 1, deoxycytidine kinase, and ribonucleotide reductase M1 gene expression levels were studied. Thirty-five patients were treated at 3 different dose levels (DL). Dose level 1 was not tolerated. Nonfrail patients continued to be treated at DL-1 (G 1250 mg/m² on day 1 and PLD 35 mg/m² on days 1 and 15). Of 10 evaluable nonfrail patients, 4 displayed dose-limiting toxicity. Frail patients were treated at DL-2 (G 1250 mg/m on day 1 and PLD 35 mg/m² on days 1 and 15). Of the 12 evaluable frail patients, 3 developed dose-limiting toxicity. Neutropenia, palmar-plantar erythrodysesthesia and stomatitis were the most common toxicities. The response rate was 42.8% (95% confidence interval [CI], 34.5%-51.1%), with 17.1% (6/35) complete responses and 25.7% (9/35) partial responses. The median progression-free survival was 7.7 months (95% CI, 2.2-13.1). The median overall survival was 13.9 months (95% CI, 9.4-18.4). The administration of PLD after gemcitabine did not influence gemcitabine pharmacokinetics or its metabolites. The addition of PLD to gemcitabine caused a larger and longer induction of the ribonucleotide reductase M1 gene. Patients with higher baseline levels of deoxycytidine kinase had longer progression-free survival. The recommended dose for a phase II study of patients with recurrent ovarian cancer having poor prognosis is PLD, 35 mg/m² on day 1, and gemcitabine, 1000 mg/m² on days 1 and 15 delivered at an FDRI of 10 mg/m per minute in 28-day cycles.
    International Journal of Gynecological Cancer 04/2011; 21(3):478-85. · 1.94 Impact Factor
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    ABSTRACT: For nearly the past two decades, cytokines (CKs) have been the only systemic treatment option available for advanced renal cell carcinoma (RCC). In recent years, tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity on this tumour. Our purpose is to describe one centre's experience with the use of CKs and TKIs in the treatment of patients with advanced RCC. This study was designed as a retrospective chart review of RCC patients who were treated with CKs and/or TKIs in our department between July 1996 and June 2008. Efficacy and toxicity were assessed using World Health Organization (WHO) criteria. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall (OS) survival. Ninety-four patients were classified into three groups depending on the modality of treatment administered: 46 were treated with CKs alone and/or chemotherapy (27 with immunotherapy, one with chemotherapy and 18 with both), 28 with TKIs alone (25 with sunitinib and 13 with sorafenib) and 20 with TKIs in second-line treatment following failure with CKs (17 with sunitinib, eight with sorafenib, four with bevacizumab and one with lapatinib). The median age was 60 years in the CK group and 65 and 62, respectively, in TKI in first and second-line treatment groups. Eighty-five percent of patients treated with CKs and 75% in the TKI group in first-line treatment and 80% in second-line treatment were men. Overall, 89% of patients had favourable risk, and 11% had intermediate risk. All patients were considered evaluable for toxicity. The main grade 3-4 (%) toxicity was asthenia for both groups, (ten in TKIs and 15 in CKs). Other grade 1-2 toxicities were mucositis (39), bleeding (8), hypertension (19), skin toxicity (33) and hypothyroidism (12.5) associated with TKIs; and anaemia (33), cough (29), asthenia (39) and emesis (14) associated with CKs. The objective response rate among 80 patients evaluable for activity was 10.6% with CKs and 46.5% and 35%, respectively, with TKIs in first- and second-line treatments. Disease stabilisation with CKs was recorded at 59% of patients and with TKIs 25% and 50% in first- and second-line treatment groups, respectively. The median progression-free survival (PFS) with CKs was 122 days [95% confidence interval (CI) 82-162] and with TKIs 201 days (65-337) in the first and 346 days (256-436) in second-line treatment groups. The median overall survival (OS) was 229 days (142-316) and 2,074 days (1,152-2,996) for patients treated with CKs and TKIs. Our results are in line with the activity and survival rates previously reported in the literature regarding the use of TKIs for patients with advanced RCC in first- and second-line treatment, which has demonstrated an acceptable toxicity level.
    Clinical and Translational Oncology 08/2010; 12(8):562-7. · 1.28 Impact Factor
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    ABSTRACT: Topotecan, a semi-synthetic camptothecin analogue with topoisomerase I interaction, has shown to be an active agent in the treatment of advanced refractory lung cancer. This paper describes the authors' experience with this drug when used as a single agent in patients (pts) with advanced non-small cell lung cancer (NSCLC) refractory to platinum- and taxane-containing chemotherapy regimens. Thirty-five patients with NSCLC refractory to previous chemotherapy and KI ≥ 60% were included in the study. Their characteristics are as follows: median age of 52 years (range 43-69) and Karnofsky PS of 70 (60-80); 27 were male and 8 were female. Twenty-one (60%) patients had adenocarcinoma; eleven (31.4%), squamous cell, and three (8.5%), undifferentiated carcinoma. There was a median of two disease sites and two prior chemotherapy regimens. Topotecan was administered at a dose of 1.25 mg/m(2) I.V. daily for 5 days, repeated every 21 days until disease progression, maximal response, or intolerable toxicity. After 73 cycles, patients received a median of 2 treatment cycles (1-9). All patients except one were considered evaluable for toxicity; eight episodes (24%) of nausea/vomiting and two episodes (6%) of grade 1-2 asthenia, respectively, were reported. Four (12%) patients developed grade 1-2 anemia and two (6%) subjects suffered grade 3 anemia. Seven (21%) patients had grade 1-2 neutropenia and one (3%) presented grade 5 neutropenia. In 33 patients evaluable for activity of the 35 subjects included in the study; one (2.8%) presented a partial response; nine (25.7%) had stable disease, and 23 (65.7%) exhibited disease progression. Median time to progression and overall survival were 54 (12-210) and 70 (12-324) days, respectively. Intravenous topotecan at that dose and administration schedule displays scant activity in terms of response rate in individuals with advanced NSCLC previously treated with platinum and taxanes. The role and usefulness of chemotherapy in this setting warrants further investigation and confirmation through comparative studies.
    Investigational New Drugs 05/2010; 29(6):1459-64. · 3.50 Impact Factor
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    ABSTRACT: The following manuscript summarises the content of the Breast Symposium that was held in May 2008 in Barcelona in which four controversies regarding the management of breast cancer were discussed. The design of the symposium included two speakers per controversy, one in favour and one diverging, and the audience had to vote before and after the presentations to assess changes in the participants' views. The four controversies included: (1) the role of non-conventional predictive factors in selecting treatment for breast cancer; (2) the role of surgery in disseminated disease; (3) are taxanes indicated in the adjuvant treatment of patients with lymph-node-negative disease?; (4) is treatment with tamoxifen (TAM) always required after surgery in patients with ductal carcinoma in situ (DCIS)? The symposium concluded with the presentation titled: 'Features of a well designed clinical trial in the adjuvant treatment of breast cancer'.
    Clinical and Translational Oncology 04/2010; 12(4):278-86. · 1.28 Impact Factor
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    ABSTRACT: Breast cancer treatment currently requires the joint efforts of a multidisciplinary team to effectively combine chemotherapy, hormone therapy, biological agents, surgery and radiation therapy when needed. To develop such a treatment plan, it is important to know the benefits as well as the potential toxic effects of each therapy. Thus, many patients with early breast cancer complain of collateral adverse events such as fatigue, nausea, vomiting, loss of libido, hot flashes, night sweats or neuropathy due to the complex therapies they are receiving. To date, the treatment of such symptoms is an important issue that greatly affects the quality of life of these patients. In this review, we report the content of a multi-expert meeting where the incidence of and medical approach to some of the most common adverse events encountered during the treatment of patients with early breast cancer were analysed.
    Clinical and Translational Oncology 01/2010; 12(1):32-42. · 1.28 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2010; 8(3):70-71.
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    Clinical and Translational Oncology 01/2010; 12(8):581-581. · 1.28 Impact Factor
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    ABSTRACT: Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing therapies and targeted therapies. Our increasing understanding of the molecular biology of metastatic disease has allowed the development of therapies aimed at specific molecular targets. Some of these have already been approved for the treatment of metastatic breast cancer in combination with cytotoxics, and others have shown promising results regarding disease-free survival, overall response rates and time to disease progression. Given the enormous amount of information about drug discovery in cancer, it is important to be familiar with the present state of the treatment of metastatic breast cancer. The purpose of this review is to provide an update on the development of some of the most promising novel agents and treatment strategies in metastatic breast cancer.
    Cancer Treatment Reviews 10/2009; 36(1):33-42. · 6.02 Impact Factor
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    ABSTRACT: The clinical decision to treat early-stage breast cancer with adjuvant chemotherapy is sometimes a difficult one because 70-80% of patients who receive chemotherapy would probably have survived without it. To help clinicians in this decision-making process, different tools or 'decision aids' have been developed for the treatment of early breast cancer over the years. Some of these tools include clinical treatment guidelines and computer-based programs as well as different prognostic and/or predictive tests such as those based on gene expression profiles or the presence minimum invasive disease. All of these tools try to individualize as much as possible the estimation of the risk of breast cancer relapse and death and to facilitate the clinical decision about giving additional treatment, and ultimately the most appropriate treatment to be given. Thus, it is important for clinicians to be aware of not only the existence of these tools or 'decision aids', but also to know how they have been developed, how frequently there are revised and if they have been validated. In order to address all these concerns, we have carried out a critical review of the most important prognostic tests and clinical guidelines for the treatment of early breast cancer. Information regarding their development process as well as frequency of revision, validations that have been performed and main limitations of each tool were gathered and critically analyzed.
    Cancer Treatment Reviews 11/2008; 34(8):701-9. · 6.02 Impact Factor
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    ABSTRACT: Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-naïve patients (n=39)<or=75 years of age, KPS>or=60% and adequate hematological, renal and hepatic function were randomly assigned to receive G 1,000 mg/m2+either V 25 mg/m2 or D 35 mg/m2 (all of which were administered i.v.) on days 1 and 8 every 21 days. Baseline characteristics were comparable in GV (n=20) and GD (n=19) groups. Results indicated objective response of 7 (35%) vs 6 (31%) patients and median time-to-treatment failure of 120 versus 90 days in the GV and GD arms, respectively. The most common non-hematological toxicities were (GV vs GD): grade 2-4 pulmonary toxicity in 1 (5%) vs 7 (37%); grade 2-3 diarrhea 0 versus 4 (21%) and edema 1 (5%) vs 3 (16%); grade 3-4 hematological toxicities occurred in 3 (15%) vs 1 (5%) patients. Our results indicate that the combination of gemcitabine/docetaxel does not have a favorable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity.
    Investigational New Drugs 02/2008; 26(1):67-74. · 3.50 Impact Factor
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    ABSTRACT: Six major randomized clinical trials evaluating the role of taxanes in the adjuvant setting of breast cancer have demonstrated significant improvements in terms of efficacy in favour of the taxane treatment arm. In all cases, different anthracycline-based regimens were used as the control arm. Nevertheless, many clinicians are still not sufficiently convinced to incorporate the routine use of taxanes in the adjuvant treatment of breast cancer. There are two main objections, first the possible lack of effectiveness of chemotherapy in hormone-receptor positive tumors and second, some of the anthracycline-based control arms used in these trials were not the optimal ones. In this review, we have searched and analyzed all randomized studies that evaluated the role of taxanes in the adjuvant setting of breast cancer patients and have reported results in terms of efficacy or tolerance. The suitability of the control arm, the prospective definition of patient's subgroups and the statistical methodology were taking into account. The objective of this review was to analyze if, at this point in time, there is sufficient evidence to support the routine use of taxanes in the adjuvant setting of breast cancer, and if it is valid for all subgroups including hormone-receptor and Her2/neu positive breast cancer patients. Other objectives of this review were to define the optimal regimen for administration of taxanes, how the tolerability of taxanes may be improved and also, to investigate any potential differences in efficacy or tolerability between docetaxel and paclitaxel.
    Cancer Treatment Reviews 09/2007; 33(5):474-83. · 6.02 Impact Factor
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    ABSTRACT: To evaluate possible improvement in objective response of adding vinorelbine (V) to the combination of cisplatin/gemcitabine (CG) in induction chemotherapy for stage III NSCLC, patients (n=154) aged < or =75 years, Karnofsky index > or =70%, were stratified by stage (IIIA versus IIIB) and randomly assigned to receive: C (50mg/m(2) i.v.) plus G (1250mg/m(2) i.v.) or CG plus V (25mg/m(2) i.v.). All drugs were administered on days 1 and 8 of an every 3-week cycle. At conclusion, local treatment (LT) with surgery and/or radiotherapy was scheduled. The results indicated that, following a median of 3 cycles, the overall efficacy was 65% in the CG and 61% in the CGV group. Most patients in both groups received radiotherapy as part of their LT. Pathological complete response was confirmed by surgery in 18% in the CG and 25% in the CGV group. Median progression-free survival was 368 days in the CG and 322 days in the CGV group. There were no statistically significant differences in toxicities between groups. We conclude that the CG and CGV combinations had similar efficacy and moderate toxicity, without accruing to the triplet combination.
    Lung Cancer 02/2007; 55(2):173-80. · 3.39 Impact Factor
  • Journal of Thoracic Oncology 01/2007; 2. · 4.47 Impact Factor
  • Journal of Thoracic Oncology - J THORAC ONCOL. 01/2007; 2.
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    ABSTRACT: INTRODUCCIÓN: La quimioterapia (QT) y la radioterapia torácica (RT-T) constituyen el tratamiento estándar para los pacientes con carcinoma de pulmón no microcítico localmente avanzado inoperable/irresecable (CPNM-I) aunque el mejor esquema de administración está por determinar. MATERIAL Y MÉTODOS: Se ha realizado un estudio prospectivo en pacientes con CPNM-I estadio IIIA o IIIB no quirúrgicos, para determinar la tolerabilidad y el control local utilizando el siguiente esquema: 7 ciclos de Docetaxel (D: 20 mg/m2) o Paclitaxel (P: 60 mg/m2) semanal, concurrente con RT-T (2 Gy diariamente de lunes a viernes, dosis total 70 Gy, durante 7 semanas) después de 3 ciclos de QT de inducción basada en cisplatino (CDDP+gemcitabina +/-vinorelbina). RESULTADOS: Desde Diciembre 1999 a Diciembre 2004, cincuenta y dos pacientes de 129 tratados con QT de inducción fueron considerados elegibles para el análisis: 27 recibieron Docetaxel y 25 Paclitaxel. La mediana de semanas de tratamiento administradas fue 5 para el D (rango 7-3) y 6 para el P (7-1). 40% (D) y 58% (P) de los pacientes en cada grupo completaron 7 semanas y las dosis programadas del tratamiento. La toxicidad registrada incluye (D/P;%): Esofagitis grado (G)I (22/18); GII (25/29), GIII (30/8), neumonitis G I-II (14/5), diarrea GI-II (14/0). La progresión local y mediana de tiempo hasta la progresión local fue 41% y 180 días para D y 46% y 240 días para P. CONCLUSIONES: Los resultados de este pequeño estudio prospectivo sugieren que la asociación concurrente de radioterapia torácica con docetaxel o paclitaxel semanal ofrece un control similar de la enfermedad así como una tendencia a una menor toxicidad no hematológica con paclitaxel.
    Oncología (Barcelona). 12/2006; 29(10).
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    ABSTRACT: La cirugía representa el tratamiento curativo de elección para los pacientes que son diagnosticados de carcinoma no microcítico de pulmón en estadio local. Sin embargo, gran parte de ellos experimentan una recurrencia de su enfermedad lo que ha llevado al empleo de opciones terapéuticas tanto locales como sistémicas con el ánimo de mejorar las posibilidades de curación. Durante las últimas décadas diversos estudios comparativos heterogéneos y varios meta-análisis publicados en los años 95 y 97 no demostraron de forma significativa una ventaja al asociar la quimioterapia y/o radioterapia adyuvante a la cirugía. Desde entonces y hasta nuestros días otros trabajos realizados con un número mayor de pacientes y empleando una quimioterapia más eficaz basada en combinaciones de platino, coinciden en describir un beneficio con su utilización aunque no de forma unánime. Más recientemente, un nuevo meta-análisis recopilando la mayoría de los estudios antes mencionados ha confirmado de forma significativa una mejoría absoluta del 4% en la supervivencia global de los pacientes sometidos a quimioterapia adyuvante, especialmente en los estadios patológicos II-III tras cirugía y tratados con regímenes que incluyen cisplatino y vinorelbina. Queda por ser determinado el papel que desempeñan otros agentes como el uracilo/tegafur así como la radioterapia en el contexto adyuvante.
    Oncología (Barcelona). 10/2006; 29(9).
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    ABSTRACT: The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; age < or = 75 years: Karnofsky performance status > or = 60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2 versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.
    Investigational New Drugs 05/2006; 24(3):241-8. · 3.50 Impact Factor