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Introducción / justificación: La evaluación de la citología in situ (ROSE, del inglés rapid on-site evaluation) se plantea como una posible mejora de la técnica diagnóstica de lesiones oncológicas tras la obtención de la muestra por punción aspirativa con aguja fina o biopsia con aguja gruesa. Esta técnica podría mejorar el método de valoración de la idoneidad de la muestra, e incluso permitir un rápido diagnóstico preliminar. Objetivo: Evaluar la eficacia, efectividad y seguridad de la citología con evaluación in situ en punción aspiración con aguja fina y biopsia con aguja gruesa ecoguiadas con respecto al protocolo de evaluación habitual. Metodología: Revisión sistemática de la literatura, incluyendo informes de evaluación de tecnologías, revisiones sistemáticas y metaanálisis. Para su elaboración se consultaron las siguientes bases de datos referenciales hasta septiembre de 2021 (con lenguaje libre y controlado): Medline (Ovid), Embase (Excerpta Medica DataBase), Cochrane Library (Cochrane Review Database), INAHTA (International HTA Database), WOS (SCI Science Citation Index) y PubMed (Ahead of print/First on line). También se exploraron EvidenceSearch y TripDataBase, así como las principales webs de agencias europeas: National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Agency for Healthcare Research and Quality (AHRQ) y la Red española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del SNS (RedETS). La selección de los estudios y el análisis de su calidad se realizaron por dos investigadores independientes. La síntesis de los resultados se llevó a cabo de forma cualitativa. La calidad de los estudios fue evaluada mediante las herramientas AMSTAR-2 para revisiones sistemáticas. Resultados: Se incluyeron 2 revisiones sistemáticas con metaanálisis. Se identificaron algunas debilidades en el análisis de la calidad de los trabajos seleccionados y la calidad general fue moderada-baja. Se evaluó la eficacia de la técnica ROSE para la indicación de sospecha de cáncer de mama, gracias a una de las revisiones sistemáticas incluidas. La diferencia en la eficacia entre las intervenciones en las que se usó esta técnica y en las que no se usó, no resultó estadísticamente significativa. Los autores de la revisión destacan que esta diferencia no significativa puede deberse a que la tasa de adecuación de las muestras sin la utilización de ROSE ya es alta por lo que el margen de posible mejora con esta técnica es limitado. Se evaluó la eficacia, la seguridad y la eficiencia de la técnica ROSE para la indicación de sospecha de cáncer de pulmón, gracias a una de las revisiones sistemáticas incluidas. En cuanto a la seguridad de la técnica en esta indicación, no se observaron diferencias significativas en la ratio de complicaciones en pacientes en los que se usó la técnica ROSE frente a pacientes en los que no se usó. En cuanto a la eficacia, todas las variables resultado mostraron valores de mayor eficacia cuando se aplicó la técnica ROSE, aunque cabe destacar la variabilidad de dichos valores entre los diferentes estudios incluidos en la revisión. Conclusiones: La técnica ROSE puede suponer una mejora en la adecuación de las muestras oncológicas y proveer un prediagnóstico de utilidad clínica para el posible tratamiento del paciente. Esta mejora es especialmente significativa en las muestras de sospecha de cáncer de pulmón, a diferencia de las pacientes con sospecha de cáncer de mama en las cuales la eficacia de la técnica no muestra diferencias significativas. Se necesitan más estudios prospectivos, controlados y aleatorizados para ambas indicaciones. Se recomienda que estos estudios homogenicen los parámetros de la técnica ROSE para evitar posibles fuentes de heterogeneidad. Además, se aconseja que estos estudios incluyan aspectos económicos que permitan la evaluación de la eficiencia.

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Background: Population-based cancer registries are required to calculate cancer incidence in a geographical area, and several methods have been developed to obtain estimations of cancer incidence in areas not covered by a cancer registry. However, an extended analysis of those methods in order to confirm their validity is still needed. Methods: We assessed the validity of one of the most frequently used methods to estimate cancer incidence, on the basis of cancer mortality data and the incidence-to-mortality ratio (IMR), the IMR method. Using the previous 15-year cancer mortality time series, we derived the expected yearly number of cancer cases in the period 2004– 2013 for six cancer sites for each sex. Generalized linear mixed models, including a polynomial function for the year of death and smoothing splines for age, were adjusted. Models were fitted under a Bayesian framework based on Markov chain Monte Carlo methods. The IMR method was applied to five scenarios reflecting different assumptions regarding the behavior of the IMR. We compared incident cases estimated with the IMR method to observed cases diagnosed in 2004–2013 in Granada. A goodness-of-fit (GOF) indicator was formulated to determine the best estimation scenario. Results: A total of 39,848 cancer incidence cases and 43,884 deaths due to cancer were included. The relative differences between the observed and predicted numbers of cancer cases were less than 10% for most cancer sites. The constant assumption for the IMR trend provided the best GOF for colon, rectal, lung, bladder, and stomach cancers in men and colon, rectum, breast, and corpus uteri in women. The linear assumption was better for lung and ovarian cancers in women and prostate cancer in men. In the best scenario, the mean absolute percentage error was 6% in men and 4% in women for overall cancer. Female breast cancer and prostate cancer obtained the worst GOF results in all scenarios. Conclusion: A comparison with a historical time series of real data in a population-based cancer registry indicated that the IMR method is a valid tool for the estimation of cancer incidence. The goodness-of-fit indicator proposed can help select the best assumption for the IMR based on a statistical argument., Subprogram "Cancer surveillance" of the CIBER of Epidemiology and Public Health (CIBERESP), MINECO/FEDER PGC2018-098860-B-I00, Andalusian Department of Health Research, Development and Innovation PI-0152/2017

The authors thank I. Linares, V. Sanz, A.B. Rodriguez, A.I. Rodriguez and E. Arias for technical advice and R. Davies for editorial assistance., The capacity of cytotoxic-T lymphocytes to recognize and destroy tumor cells depends on the surface expression by tumor cells of MHC class I molecules loaded with tumor antigen peptides. Loss of MHC-I expression is the most frequent mechanism by which tumor cells evade the immune response. The restoration of MHC-I expression in cancer cells is crucial to enhance their immune destruction, especially in response to cancer immunotherapy. Using mouse models, we recovered MHC-I expression in the MHC-I negative tumor cell lines and analyzed their oncological and immunological profile. Fhit gene transfection induces the restoration of MHC-I expression in highly oncogenic MHC-I-negative murine tumor cell lines and genes of the IFN-γ transduction signal pathway are involved. Fhit-transfected tumor cells proved highly immunogenic, being rejected by a T lymphocyte-mediated immune response. Strikingly, this immune rejection was more frequent in females than in males. The immune response generated protected hosts against the tumor growth of non-transfected cells and against other tumor cells in our murine tumor model. Finally, we also observed a direct correlation between FHIT expression and HLA-I surface expression in human breast tumors. Recovery of Fhit expression on MHC class I negative tumor cells may be a useful immunotherapeutic strategy and may even act as an individualized immunotherapeutic vaccine., FEDER funds (EU) from the Instituto de Salud Carlos III PI12/02031 PI14/01978 PI15/00528 PI17/00197 PI19/01179 PT13/0010/0039 PT17/0015/0041, Worldwide Cancer Research 15-1166, Junta de Andalucia CTS-143 CTS-3952 CVI-4740, Instituto de Salud Carlos III, Rio-Hortega Contract from ISCIII CM12/00033, ibs.Granada Fellowship 496

Journal Article; Bisphosphonates (BP) are a type of drug known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and so bone resorption. BPs are widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw (ONJ). Zoledronic acid (ZA) is an intravenous BP used in the treatment and prophylaxis of bone disease in patients with malignant tumors with bone implication. ZA is the most potent BP in clinical development. This report describes the case of a 62-year-old woman with breast cancer antecedents which relapsed, who had received a maxillary dental implant two years before the start of therapy with zoledronic acid. She later developed osteonecrosis of the jaw (ONJ), which began in the peri-implant area, and was treated for stage 3 ONJ by sub-total maxillectomy. Key words:Bisphosphonates, zoledronic acid, osteonecrosis of the jaw, peri-implantitis, maxillectomy. Yes

Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy. Yes

This work was presented, in part, as an oral communication at the ASCO 2012 annual meeting (Abstract #10500). Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; 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. Yes

Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS: Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. This work was supported by the Spanish Breast Cancer Research Group (Grupo Español de Investigación de Cáncer de Mama) (GEICAM). No funding was received for the data analyses or the writing of this manuscript. Clinical trials GEICAM/9805 and BCIRG 001 were funded by Sanofi Aventis. GEICAM/9906 and GEICAM/2003-02 were partially funded by Bristol-Myers Squibb. These funding bodies were not involved in the collection and interpretation of the data or in the decision to publish. EA and MM were also supported by FEDER (RECTICC-RD12/0036/0076). We thank all the participating patients, clinicians, GEICAM and local research staff. We thank Hosanna Soler Vila, PhD, who provided medical writing services on behalf of GEICAM. Sí

[Background]: One key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes (mRNPs). Formation of the mRNP requires the participation of a number of conserved factors such as the THO complex. THO interacts physically and functionally with the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein linking transcription, mRNA export and genome integrity. Given the link between genome instability and cancer, we have performed a comparative analysis of the expression patterns of THOC1, a THO complex subunit, and ALY in tumor samples. [Methods]: The mRNA levels were measured by quantitative real-time PCR and hybridization of a tumor tissue cDNA array; and the protein levels and distribution by immunostaining of a custom tissue array containing a set of paraffin-embedded samples of different tumor and normal tissues followed by statistical analysis. [Results]: We show that the expression of two mRNP factors, THOC1 and ALY are altered in several tumor tissues. THOC1 mRNA and protein levels are up-regulated in ovarian and lung tumors and down-regulated in those of testis and skin, whereas ALY is altered in a wide variety of tumors. In contrast to THOC1, ALY protein is highly detected in normal proliferative cells, but poorly in high-grade cancers. [Conclusions]: These results suggest a differential connection between tumorogenesis and the expression levels of human THO and ALY. This study opens the possibility of defining mRNP biogenesis factors as putative players in cell proliferation that could contribute to tumor development., This work was funded by research grants from the Spanish Ministry of Science and Innovation (BFU2007-28647-E, CSD2007-00015, PO7-CVI-02549 and ISCIII-RETIC-RD06/0020-FEDER) and the Junta de Andalucia (BIO-102). M.S. D-S was the recipient of a FPI predoctoral training grant from the Junta de Andalucía.

Background Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies. Methods Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp. Results We found no evidence of KRAS oncogenic mutations in all analyzed tumors. Conclusions This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.

14 p.-5 fig.-5 tab., [Background] The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease., [Methods] Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis., [Results] Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha., [Conclusions] Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.

This article is part of the supplement: VII Madrid Breast Cancer Conference: Changes in the treatment of breast cancer Objective: To study the efficacy of different regimens of treatment based on trastuzumab in patients with Her2+ metastatic breast cancer (MBC). Yes

Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Breast cancer survivors suffer physical impairment after oncology treatment. This impairment reduces quality of life (QoL) and increase the prevalence of handicaps associated to unhealthy lifestyle (for example, decreased aerobic capacity and strength, weight gain, and fatigue). Recent work has shown that exercise adapted to individual characteristics of patients is related to improved overall and disease-free survival. Nowadays, technological support using telerehabilitation systems is a promising strategy with great advantage of a quick and efficient contact with the health professional. It is not known the role of telerehabilitation through therapeutic exercise as a support tool to implement an active lifestyle which has been shown as an effective resource to improve fitness and reduce musculoskeletal disorders of these women. METHODS / DESIGN This study will use a two-arm, assessor blinded, parallel randomized controlled trial design. People will be eligible if: their diagnosis is of stages I, II, or IIIA breast cancer; they are without chronic disease or orthopedic issues that would interfere with ability to participate in a physical activity program; they had access to the Internet and basic knowledge of computer use or living with a relative who has this knowledge; they had completed adjuvant therapy except for hormone therapy and not have a history of cancer recurrence; and they have an interest in improving lifestyle. Participants will be randomized into e-CUIDATE or usual care groups. E-CUIDATE give participants access to a range of contents: planning exercise arranged in series with breathing exercises, mobility, strength, and stretching. All of these exercises will be assigned to women in the telerehabilitation group according to perceived needs. The control group will be asked to maintain their usual routine. Study endpoints will be assessed after 8 weeks (immediate effects) and after 6 months. The primary outcome will be QoL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0 and breast module called The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire. The secondary outcomes: pain (algometry, Visual Analogue Scale, Brief Pain Inventory short form); body composition; physical measurement (abdominal test, handgrip strength, back muscle strength, and multiple sit-to-stand test); cardiorespiratory fitness (International Fitness Scale, 6-minute walk test, International Physical Activity Questionnaire-Short Form); fatigue (Piper Fatigue Scale and Borg Fatigue Scale); anxiety and depression (Hospital Anxiety and Depression Scale); cognitive function (Trail Making Test and Auditory Consonant Trigram); accelerometry; lymphedema; and anthropometric perimeters. DISCUSSION This study investigates the feasibility and effectiveness of a telerehabilitation system during adjuvant treatment of patients with breast cancer. If this treatment option is effective, telehealth systems could offer a choice of supportive care to cancer patients during the survivorship phase. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01801527. Yes

// Maria J. Serrano 1,2,* , Francisco G. Ortega 1,* , Maria J. Alvarez-Cubero 1,2 , Rosa Nadal 3 , Pedro Sanchez-Rovira 4 , Marta Salido 5 , Maria Rodriguez 5 , Jose L. Garcia-Puche 1 , Miguel Delgado-Rodriguez 4 , Francisco Sole 6,7 , Maria A. Garcia 8 , Macarena Peran 4,10 , Rafael Rosell 9 , Juan A. Marchal 10,11 and Jose A. Lorente 1,2 1 GENYO. Pfizer-University of Granada-Andalusian Government Centre of Genomics and Oncology, Granada, Spain 2 Laboratory of Genetic Identification-UGR, Department of Legal Medicine, University of Granada, Granada, Spain 3 Hospital de Barcelona, Medical Oncology Department, Barcelona, Spain 4 University of Jaen, Division of Preventive Medicine and Public Health, CIBERESP, Jaen, Spain 5 Molecular Cytogenetics Laboratory; Pathology Department, Parc de Salut Mar-Hospital del Mar-IMIM-GRETNHE, Barcelona, Spain 6 Medicine Department. Universitat Autonoma de Barcelona, Barcelona, Spain 7 Institut de Recerca contra la Leucemia Josep Carreras, Badalona, Spain 8 Department of Oncology, Virgen de las Nieves, University Hospital, Granada, Spain 9 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain (RR); Pangaea Biotech SL, USP Dexeus University Institute, Barcelona, Spain (RR, MAM) 10 Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada, Spain 11 Department of Human Anatomy and Embryology, University of Granada, Granada, Spain * These authors contributed equally to this work Correspondence: Jose A Lorente, email: // Juan Antonio Marchal, email: // Keywords : Breast Cancer, Circulating Tumor Cells, EGFR, Epithelial-Mesenchymal Transition, Vimentin, Slug, Bcl-2, Apoptosis Received : May 16, 2014 Accepted : July 13, 2014 Published : July 14, 2014 Abstract Circulating tumor cells (CTCs) are frequently associated with epithelial-mesenchymal transition (EMT).The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.