Imaginando el futuro / Looking to the future

Presentamos la visión futurista que de su especialidad tienen 7 líderes de opinión estrechamente comprometidos con la patología mamaria. Las especialidades incluidas fueron radiología, patología, cirugía, cirugía plástica, medicina nuclear, oncología médica y oncología radioterápica. Los autores plasman, en este artículo, sus opiniones y criterios respecto a los avances que vislumbran en su futuro profesional.Conceptos clave como sistemas de cribado sin radiación, transcriptómica clínica, diagnóstico funcional del tumor, inteligencia artificial, navegación intraoperatoria, biopsia líquida, ADN tumoral circulante, reconstrucción con técnicas microquirúrgicas avanzadas, hipofraccionamiento extremo o teragnosis, son algunos de los conceptos presentados y discutidos.Los autores justifican sus puntos de vista, abriendo líneas de trabajo a tener en cuenta para optimizar esfuerzos y el conocimiento futuro. (AU)

We present the futuristic vision of their specialty of seven opinion leaders closely involved in breast pathology. The specialties were radiology, pathology, surgery, plastic surgery, nuclear medicine, medical oncology, and radiation oncology. In this article, the authors express their opinions and criteria regarding the advances they foresee for their professional future.Key concepts such as radiation-free screening systems, clinical transcriptomics, functional tumor diagnosis, artificial intelligence, intraoperative navigation, liquid biopsy, circulating tumor DNA, reconstruction with advanced microsurgical techniques, extreme hypofractionation or theragnosis are some of the concepts presented and discussed.The authors justify their points of view, suggesting lines of work to optimize efforts and future knowledge. (AU)

The economic burden of disease of epithelial ovarian cancer in Spain: the OvarCost study.

OBJECTIVE: To assess the economic burden of epithelial ovarian cancer (EOC) in incident patients and the burden by disease stage in Spain. METHODS: We developed a Markov model from a social perspective simulating the natural history of EOC and its four stages, with a 10-year time horizon, 3-week cycles, 3% discount rate, and 2016 euros. Healthcare resource utilization and costs were estimated by disease stage. Direct healthcare costs (DHC) included early screening, genetic counselling, medical visits, diagnostic tests, surgery, chemotherapy, hospitalizations, emergency services, and palliative care. Direct non-healthcare costs (DNHC) included formal and informal care. Indirect costs (IC) included labour productivity losses due to temporary and permanent leaves, and premature death. Epidemiology data and resource use were taken from the literature and validated for Spain by the OvarCost group using a Delphi method. RESULTS: The total burden of EOC over 10 years was 3102 mill euros: 15.1% in stage I, 3.9% in stage II, 41.0% in stage III, and 40.2% in stage IV. Annual average cost/patient was €24,111 and it was €8,641; €14,184; €33,858, and €42,547 in stages I-IV, respectively. Of total costs, 71.2% were due to DHC, 24.7% to DNHC, and 4.1% to IC. CONCLUSIONS: EOC imposes a significant economic burden on the national healthcare system and society in Spain. Investment in better early diagnosis techniques might increase survival and patients' quality of life. This would likely reduce costs derived from late stages, consequently leading to a substantial reduction of the economic burden associated with EOC.

ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.

BACKGROUND: Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. METHODS: Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). RESULTS: Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. CONCLUSION: Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.

Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study.

The objective of this study was to determine the conversion rate of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) between primary tumors and metastatic lesions in advanced breast cancer. Patients with suspected diagnosis of locally recurrent or metastatic breast cancer, either at first relapse or after successive disease progressions, who had an appropriately preserved sample from a primary tumor and were scheduled for a biopsy of the recurrent lesion, were included. Blinded determinations of receptor status on paired samples were performed by immunohistochemistry and fluorescence in situ hybridization at a central laboratory and compared with those performed locally. Overall, 196 patients were included and 184 patients were considered evaluable. Reasons for non-evaluability included the inability to perform biopsy (n = 4) or biopsy results showing normal tissue (n = 3), benign disease (n = 3) or a second neoplasia (n = 2). Conversion rates determined at local level were higher than those determined centrally (HER2: 16 vs. 3 %, ER: 21 vs. 13 %, PR: 35 vs. 28 %, respectively). There was substantial agreement regarding the expression of HER2 in primary tumors and metastases, and ER at metastases, between local and central laboratories. PR at any site and ER at primary site showed moderate agreement. Oncologists altered their treatment plans in 31 % of patients whose tumor subtype had changed. These results reinforce the recommendation for performing confirmatory biopsies of metastases, not only to avoid misdiagnosis of breast cancer relapse, but also to optimize treatment (clinicaltrials.gov identifier: NCT01377363).