Laura G Estévez

Hospital Universitario Miguel Servet, Caesaraugusta, Aragon, Spain

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Publications (40)174.09 Total impact

  • L. G. Estévez · E. García · M. Hidalgo ·
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    ABSTRACT: Aberrations in the PI3K signaling pathway are frequentlyobserved in patients with breast cancer. Because of that, PI3K inhibitors are attractive options for the treatment of breast cancer because PI3K is the most proximal component of the pathway other than receptor tyrosine kinases. Buparlisib is a potent and highly specific oral pan-class I PI3K inhibitor, which is currently under investigation in patients with breast cancer. In this article, we describe the PI3K signaling pathway, the prognostic value of PI3K pathway mutations, as well as the mechanism of action of buparlisib. Lastly, we discuss preliminary results of preclinical and clinical studies showing the efficacy and safety profile of this agent in breast cancer patients. © 2015 Federación de Sociedades Españolas de Oncología (FESEO)
    Clinical and Translational Oncology 10/2015; DOI:10.1007/s12094-015-1410-z · 2.08 Impact Factor

  • Spanish Society of Medical Oncology Meeting; 10/2014
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    ABSTRACT: Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS. Patients with HER2 positive DCIS received 1,500 mg daily of lapatinib for four consecutive weeks prior to surgical resection. Magnetic resonance imaging (MRI) was used to determine changes in tumor volume. The molecular effects of lapatinib on HER2 signaling (PI3K/AKT and RAS/MAPK pathways), cell proliferation (Ki67 and p27) and apoptosis (TUNEL) were determined in pre and post-lapatinib treatment samples. A total of 20 patients were included. Lapatinib was well tolerated with only minor and transient side effects. The agent effectively modulated HER2 signaling decreasing significantly pHER2 and pERK1 expression, together with a decrease in tumor size evaluated by MRI. There was no evidence of changes in Ki67. Four weeks of neoadjuvant lapatinib in patients with HER2-positive DCIS resulted in inhibition of HER2 and RAS/MAPK signaling pathway. Trial registration 2008-004492-21 (Registered June 25th 2008).
    Breast cancer research: BCR 09/2014; 16(4):R76. DOI:10.1186/bcr3695 · 5.49 Impact Factor
  • LG Estevez · A. Suarez · I. Calvo · M. Fernandez-Abad · S. Perea · M. Hidalgo ·

    Cancer Research 03/2014; 73(24 Supplement):P4-15-09-P4-15-09. DOI:10.1158/0008-5472.SABCS13-P4-15-09 · 9.33 Impact Factor

  • Cancer Research 12/2012; 72(24 Supplement):P5-18-15-P5-18-15. DOI:10.1158/0008-5472.SABCS12-P5-18-15 · 9.33 Impact Factor
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    ABSTRACT: Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.
    Breast Cancer Research and Treatment 10/2012; 136(2). DOI:10.1007/s10549-012-2100-y · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND: Use of breast magnetic resonance imaging (MRI) to detect breast cancer has generated significant debate. We analyze the role of breast MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, we correlate the detection of new foci with tumor pathological features. METHODS: Early breast carcinoma patients that had undergone an MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki67. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features. RESULTS: Data from 98 patients have been analyzed: median age 49 years (range 35-79); carcinoma type: (a) infiltrative ductal carcinoma (n = 73, 74 %), (b) infiltrative lobular cancer (n = 12, 12 %), (c) ductal carcinoma in situ (n = 6, 6 %); amplified HER2 (n = 18, 18 %); grade III (n = 33, 33 %); Ki67 ≥ 25 % (n = 33, 33.67 %); positive ER and PR (n = 79, 80 %); triple negative tumors (n = 8, 8 %). MRI detected additional disease in 38 cases (39.58 %), and 20 led to an additional biopsy (20.4 %). Thirty-eight patients (39 %) underwent mastectomy. We found a statistically significant correlation between new foci in MRI and high Ki67 ≥ 25 % (p < 0.005). No other statistically significant correlation was established. CONCLUSION: MRI detected additional disease in 39 % cases, requiring an additional biopsy 20 %. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI.
    Clinical and Translational Oncology 08/2012; 15(3). DOI:10.1007/s12094-012-0899-7 · 2.08 Impact Factor
  • L Estévez · I Alvarez · I Tusquets · M.A. Seguí · M Muñoz · Y Fernández · A Lluch ·
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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; 39(2). DOI:10.1016/j.ctrv.2012.06.003 · 7.59 Impact Factor
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    ABSTRACT: Third-generation aromatase inhibitors (AIs) have proven to be superior to tamoxifen in terms of time to disease progression in patients with hormone receptor (HR) positive (HR+) status and, nowadays, are used in the adjuvant and neoadjuvant settings, and first-line therapy for advanced breast cancer. Letrozole is a third generation AI, as are anastrozole and exemestane. In the past, clinical studies had demonstrated that letrozole was effective as a second-line treatment of metastatic breast cancer. In this paper, pharmacokinetic and pharmacodynamic properties of letrozole are reviewed along with its activity in preclinical and clinical settings. Additionally, the results of important clinical trials such as Breast International Group (BIG) 1-98, which tested the optimal initial adjuvant endocrine treatment and the sequential therapy with letrozole and tamoxifen, MA-17 that evaluates the benefits of extended adjuvant therapy, and other important studies in advanced and neoadjuvant disease, are reviewed. Safety comparisons of treatments are also addressed. Interestingly, about 50% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers are HR+. However, HER2 positivity is a marker of antiestrogen treatment resistance. Because of this, a dual treatment is a logical approach when both receptors are overexpressed. The combination of lapatinib and letrozole leads to a significant improvement in the overall disease outcome. Also, the combination of everolimus plus letrozole has been tested in this setting. In fact, the coadministration of both agents seems to increase the efficacy of letrozole in newly-diagnosed HR+ patients. Once resistance to sequential trastuzumab and AI as monotherapy has been found, trastuzumab and letrozole combined in HR+ and HER2+ patients with advanced breast cancer can overcome resistance to both drugs administered as single agents, according to recently reported results.
    Advances in Therapy 11/2011; 28(12):1045-58. DOI:10.1007/s12325-011-0075-4 · 2.27 Impact Factor

  • Cancer Research 04/2011; 70(24 Supplement):P2-06-17-P2-06-17. DOI:10.1158/0008-5472.SABCS10-P2-06-17 · 9.33 Impact Factor

  • San Antonio Breast Cancer Symposium; 12/2010
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    ABSTRACT: Patients with metastatic breast cancer have a wide number of treatment options, including medical, surgical, and supportive care measures. Treatment decisions are based in predictive and prognostic factors and the informed choice of the patients. SEOM has elaborated these guidelines with evidence-based recommendations for the diagnostic work-up, treatment (chemotherapy, endocrine therapy and targeted therapies) and supportive care for the management of these patients.
    Clinical and Translational Oncology 11/2010; 12(11):719-23. DOI:10.1007/s12094-010-0585-6 · 2.08 Impact Factor
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    ABSTRACT: DCIS is a genetically diverse group of diseases with different prognosis. The similarities between DCIS and ductal infiltrating carcinoma (DIC) suggest that the key step in tumorigenesis is the transformation from high grade ductal hyperplasia to DCIS. The prognostic factors of DCIS include anatomo-pathologic factors, age and molecular factors. The key questions for DCIS management include: which patients are more likely to present an invasive failure; in which an excision is sufficient and who can be spared from radiation therapy. The role of post operative radiation therapy to reduce by 50-60% ipsilateral invasive and non-invasive local failure has been established in four randomized clinical trials. The question whether radiation therapy can be avoided in some patients remains controversial. Treatment with tamoxifen should be recommended to patients with estrogen receptor positive tumors who have been treated with conservative surgery. However, data from randomized trials suggest that addition of tamoxifen to locoregional treatment decreases the recurrence rate of invasive cancer as well as contralateral tumors. Sentinel lymph node biopsy is recommended for patients with clinically palpable, large DCIS in which the risk of microinvasion is high as well as in extensive DCIS requiring mastectomy. Mammography continues to be the best method to detect DCIS. Newer digital mammography improves the detection of microcalcifications. Current ultrasound can detect associated invasive cancer. MRI is also useful in DCIS. Combined with mammography, MRI increases the diagnoses of DCIS. Current trend includes the use of radiology guided-vacuum assisted-large bore needles that allow obtaining larger amounts of tissue, improving diagnostic yield.
    Cancer Treatment Reviews 05/2010; 36(7):507-17. DOI:10.1016/j.ctrv.2010.03.007 · 7.59 Impact Factor
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    ABSTRACT: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.
    Clinical and Translational Oncology 02/2009; 11(1):54-9. DOI:10.1007/s12094-009-0311-4 · 2.08 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. DOI:10.1016/j.ctrv.2008.04.002 · 7.59 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the efficacy and safety of capecitabine in combination with vinorelbine in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. In this prospective, multicenter, open-label phase II trial, patients received capecitabine (2000 mg/m2 daily, taken in 2 oral doses) on days 1-14 and vinorelbine (25 mg/m2 intravenous infusion) on days 1 and 8. Cycles were repeated every 3 weeks up to a maximum of 6 cycles, unless disease progression or unacceptable toxicity occurred or patient consent was withdrawn. Thirty-one patients were included and received 152 cycles of chemotherapy, with a median of 3 cycles per patient. All patients were evaluated for efficacy and toxicity in an intent-to-treat analysis. The overall response rate was 49% (95% CI, 30%-67%), including 4 complete (13%) and 11 partial (36%) responses. With a median follow-up time of 9 months, the median time to disease progression was 7.6 months (95% CI, 5.7-9.8 months), and the median survival time was 27.2 months. The most frequent severe hematologic toxicities were neutropenia (48% of patients) and leukopenia (10% of patients). Vomiting (16% of patients) was the most common nonhematologic toxicity, while asthenia, bone pain, dyspnea, plantar-palmar erythrodysesthesia, nausea, and transaminase elevation were observed in 6%-10% of patients. There was 1 death from septic shock. Capecitabine in combination with vinorelbine is an effective and safe schedule for patients with MBC pretreated with anthracycline- and taxane-containing regimens.
    Clinical Breast Cancer 05/2008; 8(2):149-54. DOI:10.3816/CBC.2008.n.015 · 2.11 Impact Factor
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    ABSTRACT: Combined treatments together with surgery, radiotherapy, chemotherapy, and endocrine therapy have contributed substantially to the improved survival rate in breast cancer. For more than 2 decades, tamoxifen has been the standard endocrine agent for hormone receptor-positive tumors. Third-generation aromatase inhibitors have, however, now proven to be superior to tamoxifen in the adjuvant and, more recently, the neoadjuvant treatment of postmenopausal patients. They have especially improved the surgical management of large or inoperable locally advanced breast tumors. Other advantages of neoadjuvant endocrine therapy are just emerging, but there are still many unanswered questions regarding its optimal use in this setting. A need to define how to select the patients who will benefit most from these therapies, the optimal duration of treatment, the best method to evaluate the treatment response achieved, the existence of predictive factors for response, or the superiority of certain endocrine agents over others has been observed. Other questions regarding which complementary local and systemic treatments should be administered after neoadjuvant endocrine therapy or which efficacy endpoints should be evaluated in clinical trials are also of interest. To answer as many of these questions as possible, we have carried out a critical analysis of the current literature on the use of endocrine therapy in the neoadjuvant setting of breast cancer. In this review, we outline the rationale for its use, and consider data published to date to further clarify how to optimize its administration.
    Anti-Cancer Drugs 05/2008; 19(4):339-47. DOI:10.1097/CAD.0b013e3282f97f75 · 1.78 Impact Factor
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    ABSTRACT: This review examines all randomized studies that evaluated the role of taxanes in the neoadjuvant treatment of breast cancer and have reported results in terms of efficacy and tolerance. The primary objective of this review was to evaluate whether, at this point in time, there is sufficient evidence to support the routine use of taxanes in the neoadjuvant treatment of breast cancer. Other objectives were to determine the optimal schedule in which to administer taxanes and anthracyclines and whether the addition of other antitumor drugs improves the efficacy of these anthracycline/taxane-based schedules. A literature search revealed 9 major randomized clinical trials published to date. To facilitate analysis, they were classified according to their protocol design. Five trials evaluated the effect of the addition of a taxane to an anthracycline-based schedule, either concomitantly or sequentially. The remaining 4 trials contained taxanes in both treatment arms in an attempt to optimize the administration schedule of anthracyclines and taxanes, or to improve efficacy by adding a further antitumor drug. This type of analysis has provided the opportunity to draw some conclusions regarding the optimal use of taxanes.
    Clinical Breast Cancer 11/2007; 7(10):764-74. DOI:10.3816/CBC.2007.n.037 · 2.11 Impact Factor
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    ABSTRACT: At the present time, there is not a standard regimen in upfront metastatic setting for breast cancer. A wide variety of regimens which includes anthracyclines, taxanes, gemcitabine or capecitabine are currently used, however, there is evidence to support the use of many of these drugs in early breast cancer and consequently limiting their use in first line treatment. The aim of this review is to evaluate every randomized phase III trials conducted in first line metastatic breast cancer. For this reason, all randomized studies that evaluated the role of chemotherapy in advanced breast cancer were analyzed and classified according to their protocol design. So far, sixteen major randomized clinical trials have evaluated the role of chemotherapy as front line in metastatic breast cancer. Some of them have analyzed a different anthracyclines-based regimen as the control arm versus new combinations or new drugs. In others, the aim is to evaluate the most effective therapy after progression to an adjuvant anthracyclines-containing regimen. The suitability of the control arm, the prospective definition of patient's subgroups as well as the statistical methodology have been taken into account.
    Anti-Cancer Drugs 09/2007; 18(7):843-59. DOI:10.1097/CAD.0b013e3280bad81a · 1.78 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. DOI:10.1016/j.ctrv.2007.04.006 · 7.59 Impact Factor

Publication Stats

347 Citations
174.09 Total Impact Points


  • 2012
    • Hospital Universitario Miguel Servet
      Caesaraugusta, Aragon, Spain
  • 1999-2009
    • Fundación Jiménez Díaz
      Madrid, Madrid, Spain
  • 1998-2005
    • Universidad Autónoma de Madrid
      • Department of Pathology
      Madrid, Madrid, Spain
  • 2004
    • Universidad de Jaén
      Jaén, Andalusia, Spain