Iridium thin-film coatings for the BabyIAXO hybrid X-ray optic.

Reflective coatings are an essential feature of X-ray telescopes. Their overall performance relies heavily on substrate compatibility and how well they conform to the optics assembly processes. We use X-ray reflectometry (XRR) to demonstrate the compatibility of shaping flat substrates coated with iridium, and show that specular and nonspecular reflectance before and after shaping is on par with traditional hot-slumped coated substrates. From 1.487 and 8.048keV measurements, we find that the substrates have rms roughness of 0.38nm and magnetron sputtered iridium deposits with rms surface roughness of 0.27-0.35nm. A hydrocarbon overlayer from atmospheric contamination is present with a thickness of 1.4-1.6nm and a density of 1.2-1.6g/cm3. Both the traditional hot slumped and the flat substrates undergoing post-coating shaping have a similar characteristic surface morphology and are equally well-suited for use with X-ray optics. Finally, we demonstrate by simulation the improved effective area achieved by using a low-Z overlayer, and illustrate the performance of a hybrid optic coated with optimized bilayers for a Primakoff axion spectrum emitted by the sun.

Resilience of river flow regimes.

Landscape and climate alterations foreshadow global-scale shifts of river flow regimes. However, a theory that identifies the range of foreseen impacts on streamflows resulting from inhomogeneous forcings and sensitivity gradients across diverse regimes is lacking. Here, we derive a measurable index embedding climate and landscape attributes (the ratio of the mean interarrival of streamflow-producing rainfall events and the mean catchment response time) that discriminates erratic regimes with enhanced intraseasonal streamflow variability from persistent regimes endowed with regular flow patterns. Theoretical and empirical data show that erratic hydrological regimes typical of rivers with low mean discharges are resilient in that they hold a reduced sensitivity to climate fluctuations. The distinction between erratic and persistent regimes provides a robust framework for characterizing the hydrology of freshwater ecosystems and improving water management strategies in times of global change.

Shifts in flood generation processes exacerbate regional flood anomalies in Europe.

Anomalies in the frequency of river floods, i.e., flood-rich or -poor periods, cause biases in flood risk estimates and thus make climate adaptation measures less efficient. While observations have recently confirmed the presence of flood anomalies in Europe, their exact causes are not clear. Here we analyse streamflow and climate observations during 1960-2010 to show that shifts in flood generation processes contribute more to the occurrence of regional flood anomalies than changes in extreme rainfall. A shift from rain on dry soil to rain on wet soil events by 5% increased the frequency of flood-rich periods in the Atlantic region, and an opposite shift in the Mediterranean region increased the frequency of flood-poor periods, but will likely make singular extreme floods occur more often. Flood anomalies driven by changing flood generation processes in Europe may further intensify in a warming climate and should be considered in flood estimation and management.

Characterizing hydrograph recessions from satellite-derived soil moisture.

Hydrograph recessions, usually described through a power-law function of river flows, are among the most widely utilized hydrological signatures. Whereas theories explaining the genesis of recession exponents have been recently developed, ongoing discussions on the physical meaning and suitable proxies of recession coefficients suggest their linkage to soil moisture states of whole river basins. This work investigates the possibility to explain hydrograph recession coefficients by means of satellite-derived soil moisture products such as the Soil Water Index of Copernicus Global Land Service. Analyses of basin-averaged Soil Water Index, computed for eleven river basins from the Central and Eastern United States with varied climates and landscapes, reveal the existence of an inverse relation between mean soil moisture and its variability in time, and provide a glance into the variability of river flows. A visible signature of satellite-derived soil moisture conditions on the values of the recession coefficient as well emerges when statistics of the Soil Water Index are paired with recession properties obtained by means of hydrograph recession analysis. In particular, drier river basins characterized by larger soil moisture variability tend to exhibit larger and more variable recession coefficients. These results suggest reliability of existing conjectures about the role of soil moisture for determining recession properties, and indicate that satellite-derived products can inform understanding of the intrinsic variability of the hydrologic response in river basins.

Cytokines, thyroid diseases and thyroid cancer.

Cytokines are molecules that influence activation, growth, and differentiation of several target cells. They are proinflammatory mediators, regulate the systemic inflammatory response, playing a crucial role in autoimmune thyroid diseases, and modulate development and growth of both normal and neoplastic thyroid cells. In addition cytokines, as well as chemokines, have been shown to generate antitumor response. In patients with thyroid cancer, cytokines are useful as serum biomarkers, and should be a part of multi-analyte assay in the clinical evaluation of patients with indeterminate fine-needle aspiration cytology. Finally, several cytokines, such as interleukin-6 (IL-6), leukemia inhibiting factor (LIF), and thyroid transcription factor-1 (TTF-1) are expressed in thyroid cancer cell lines, and they can be used for evaluating the inhibitory effects of several drugs in redifferentiation therapies. This review reports the latest advances in defining the actions of cytokines, and resumes the relationship between cytokines, thyroid diseases and thyroid cancer.

Hypoxemia and hypoventilation syndrome improvement after laparoscopic bariatric surgery in patients with morbid obesity.

BACKGROUND: The objective of this study was to evaluate the relationship between oxygen partial pressure (pO(2)), awake oxymetric saturation (SpO(2)), body mass index (BMI), and percentage of excess weight loss (EWL) in extremely severe obesity (BMI >50 kg m(-2)) and hypoxemia, before and after laparoscopic Roux-en-Y gastric bypass. PATIENTS AND METHODS: A group of 11 obese patients aged 41.2 + or - 10.2 years (4 men, 7 women, median BMI=52.3 kg/m(2), range 50.2-57.1) were prospectively enrolled in the study. BMI, arterial blood gas measurements, and spirometry were obtained before and after (6 and 12 months) surgery. RESULTS: The main preoperative parameters were SpO(2)=88.3 + or - 3.9%, predicted forced vital capacity (FVC)=84.5 + or - 8.3%, predicted forced expiratory volume exhaled in one second (FEV1)=79.9+/-10.1%. No relationship (p>0.01) was found between BMI, SpO(2), and FEV1. A significant correlation between SpO(2) and both paO(2) (R=0.74, p=0.009) and EWL (R=-0.75, p=0.008) was found. Three, 6, and 12 months after surgery EWL was 18.9%, 26.4%, and 39.6% (p<0.001), respectively. At one-year follow-up SpO(2), FVC, and FEV1 were 96.2 + or - 3.2% (p<0.001), 112.3 + or - 9.9% (p<0.001), and 101.6 + or - 18.8% (p=0.003), respectively. CONCLUSION: In patients with extremely severe obesity, bariatric surgery may improve significantly both SpO(2) and spirometric parameters, and EWL represents the factor that impacted the results.

Diagnosis of Malignant Pleural Effusion Using CT Scan and Pleural-Fluid Cytology Together. A Preliminary Case-Control Study.

BACKGROUND/AIM: The purposes of this study were to evaluate the usefulness of chest computed tomographic (CT) scan plus pleural fluid cytology (PFC) together in patients with malignant pleural effusion (PE), and to compare the results of these diagnostic tools in patients with malignant PE due to non-small-cell lung cancer and pulmonary metastases from other malignancies. PATIENTS AND METHODS: The medical records of 185 patients with PE, who underwent chest CT, PFC and video-assisted thoracoscopy (VATS) thoracentesis followed by VATS-guided biopsy for diagnostic purpose, were reviewed. At the final diagnosis, 123 (66.5%) patients had malignant PE (cases), and 62 (33.5%) had benign PE (controls). RESULTS: Overall, the sensitivity, specificity, and accuracy of CT and PFC were 65.0% vs. 67.5% 98.4% vs. 98.4%, and 76.2% vs. 77.8%, respectively. The combination of CT plus PFC significantly improved sensitivity (86.2%, p=0.003) and accuracy (90.8%, p=0.02). CONCLUSION: CT and PFC used together may lead to approximately 100% specificity and >90% sensitivity in distinguishing between benign and malignant PE.

Diagnostic Accuracy of Pleural Fluid Cytology, Carcinoembryonic Antigen and C-Reactive Protein Together in Patients With Pulmonary Metastases and Malignant Pleural Effusion.

BACKGROUND/AIM: Pleural effusion (PE) has a heterogeneous aetiology, and differential diagnosis between benign and malignant disease may require invasive procedures in up to 60% of cases. The sensitivity of pleural cytology is limited, and several strategies have been tested to reduce the need of invasive diagnostic approaches. The aim of this study was to evaluate the usefulness of pleural fluid cytology, compared to, and combined with, carcinoembryonic antigen (CEA), C reactive protein (CRP), and lactate dehydrogenase (LDH) assay of pleural fluid (PF) in patients with a history of cancer, exudative non-purulent PE, and suspicion of malignant PE on imaging studies. PATIENTS AND METHODS: The medical records of 40 patients with pulmonary metastases and malignant PE, and 57 controls with benign exudative PE were reviewed. All the patients underwent pleural cytology and CEA, CRP, and LDH assay before VATS-guided biopsy. RESULTS: The sensitivity and specificity were 55.0% and 98.2% (cytology), 35.0% and 98.2% (CEA), 92.5% and 71.9% (CRP), 70.0% and 54.4% (LDH). The multivariate analysis excluded LDH, and the final AUC (cytology+CEA+CRP) was 0.894. CONCLUSION: In all patients with a history of cancer and PE of uncertain origin, the combination of PF cytology plus pleural CEA and CRP assay together should be suggested to recognize malignant plural effusion (MPE), minimising the use of unnecessary invasive investigations.

Incidence of arm lymphoedema following sentinel node biopsy, axillary sampling and axillary dissection in patients with breast cancer.

The aim of this study was to compare the incidence of lymphoedema after different treatments of the axilla in patients with breast cancer (BC). Medical records of 205 women (median age 61 years, range 26-72 years) who underwent curative surgery for primary BC were reviewed. According to the treatment of the axilla, the study population was divided into four age- and stage-matched groups of patients: Group A (N=54 patients), sentinel node biopsy (SLNB) alone; Group B (N=48 patients), SLNB followed by axillary node (AN) sampling using ultrasound scissors (harmonic scalpel); Group C (N=53 patients), AN dissection using ultrasound scissors; Group D (N=50 patients), traditional AN dissection. The median follow-up was 22 months (range 18-28 months). The intraoperative frozen section of SLNB (Groups A and B) showed 32 out of 102 (31.4%) patients with metastasis to AN, while final pathology showed AN metastases in 20, 17, 16 and 17 patients of groups A, B, C and D, respectively (p=NS). The sensitivity of SLNB alone was 80% and that of SLNB followed by AN sampling was 95% (p=NS). At follow-up patients with lymphoedema were 2 (3.7%), 2 (4.2%), 3 (5.6%) and 8 (16%) in groups A, B, C and D, respectively (p=NS). In conclusion, AN sampling is a sensitive and low-morbidity procedure which, in conjunction with the use of harmonic scalpel, may reduce the onset of arm lymphoedema.

Causative classification of river flood events.

A wide variety of processes controls the time of occurrence, duration, extent, and severity of river floods. Classifying flood events by their causative processes may assist in enhancing the accuracy of local and regional flood frequency estimates and support the detection and interpretation of any changes in flood occurrence and magnitudes. This paper provides a critical review of existing causative classifications of instrumental and preinstrumental series of flood events, discusses their validity and applications, and identifies opportunities for moving toward more comprehensive approaches. So far no unified definition of causative mechanisms of flood events exists. Existing frameworks for classification of instrumental and preinstrumental series of flood events adopt different perspectives: hydroclimatic (large-scale circulation patterns and atmospheric state at the time of the event), hydrological (catchment scale precipitation patterns and antecedent catchment state), and hydrograph-based (indirectly considering generating mechanisms through their effects on hydrograph characteristics). All of these approaches intend to capture the flood generating mechanisms and are useful for characterizing the flood processes at various spatial and temporal scales. However, uncertainty analyses with respect to indicators, classification methods, and data to assess the robustness of the classification are rarely performed which limits the transferability across different geographic regions. It is argued that more rigorous testing is needed. There are opportunities for extending classification methods to include indicators of space-time dynamics of rainfall, antecedent wetness, and routing effects, which will make the classification schemes even more useful for understanding and estimating floods. This article is categorized under:Science of Water > Water ExtremesScience of Water > Hydrological ProcessesScience of Water > Methods.

Bone Mineral Density as a Potential Predictive Factor for Luminal-type Breast Cancer in Postmenopausal Women.

BACKGROUND/AIM: We performed a case-control study to evaluate whether bone mineral density (BMD) can be considered a potential predictive factor for luminal-type breast cancer (BC), that could be useful in constructing a predictive risk model. MATERIALS AND METHODS: The medical records of 297 postmenopausal women with luminal-type node-negative BC who underwent lumbar-spine dual-energy X-ray absorptiometry (DXA) with BMD measurement before surgery, were analyzed and compared with those of 297 age-matched randomly selected healthy controls. The correlations between women's reproductive history, including the age at menarche and menopause, parity, oral contraceptives and hormone replacement therapy (HRT) use, the results of DXA, and BC risk were evaluated in univariate and multivariate analyses. RESULTS: Overall, 168 (28.3%) women had osteoporosis and/or osteopenia (low BMD). Both bone alterations were protective factors for BC, especially when they were considered together (p=0.001). Only the interval between menarche and menopause (MMI), dichotomized at 37.5 years as an optimal cut-off, and the HRT use reached a statistical significance (p<0.01) as risk factors. The three parameters were independent because they remained significant in the stepwise logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) obtained with the model was 0.694 (95%CI=0.694-0.731). CONCLUSION: This hypothesized predictive model is fairly accurate and could identify patients at increased risk of developing luminal-type BC in a population of postmenopausal women who performed DXA, simply based on their history.

Analysis of Factors Affecting Short-term Results in Elderly Patients Undergoing Elective Surgical Resection for Stage I-II Colon Cancer.

AIM: The aim of this study was to analyze the influence of comorbidities and to compare the short-term results of elective surgical resection of stage I-II colon adenocarcinoma in elderly (≥65 years) versus younger patients. PATIENTS AND METHODS: Two groups of sex-matched younger and older patients were compared: Group A: N=36, median age 58 (range=43-65) years; and group B: N=67, median age 73 (range=66-86) years. RESULTS: Overall, 71 out of 103 (68.9%) patients had one or more comorbidities. A greater number of older patients had an American Society of Anesthesiologists (ASA) score >2 (p=0.004) and were on multiple medications (polypharmacy) (p=0.016), but the distribution of the other parameters was similar (p≥0.05). Intra- and postoperative complications in group A vs. B occurred in 25.0% vs. 26.9%, and 47.2% vs. 64.2%, respectively (p≥0.05). CONCLUSION: Elderly patients with colon cancer scheduled to elective surgical resection should not be considered at increased risk of intra- or short-term postoperative complications with respect to younger patients. However, they require careful individual preoperative evaluation because they are usually polypharmacy users and have a higher ASA score.

Parathyroid cancer: etiology, clinical presentation and treatment.

Parathyroid carcinoma (PC) is an uncommon finding, accounting for only 1-2% of patients with primary hyperparathyroidism (HPT), but a relatively higher incidence has been reported in Italy and Japan. The etiology of the tumour remains unclear, but molecular analysis studies have hypothesised the involvement of mutations of several genes in the pathogenesis of PC, including the oncogene cyclin Dl or PRADI located at the chromosome 13, the retinoblastoma and the p53 tumour suppressor gene. The clinical presentation of patients with PC is mainly related to the increased secretion of PTH rather than to the tumour burden. The pre-operative diagnosis of malignancy is very difficult to obtain, and, thus, intra-operative recognition of PC is mandatory. However, reliable signs of malignancy are rarely detectable. Probably, only vascular invasion, that correlates with tumour recurrence and metastases, should be considered useful in confirming malignancy, although both Ki-67 and Cyclin D1 have been recently used to aid in the definitive diagnosis. The en bloc resection of the tumour, together with ipsilateral thyroid lobe and adjacent structures, only if involved, avoiding any capsular rupture of the mass, represents the gold standard of surgical treatment of patients. Although the PC has traditionally been considered as a radioresistant tumour, there are some retrospective data holding a possible benefit from post-operative irradiation. No cytotoxic regimen with proven efficacy is currently available for patients with PC, but since hypercalcemia is ultimately the most frequent cause of death, several studies have suggested the usefulness of bisphosphonates (i.e., clodronate, pamidronate and zoledronate), calcitonin, and calcimimetic agents (i.e., cinacalcet) in patients with PC and severe hypercalcemia. In conclusion, PC is a rare malignancy and the NCDB survey reports an overall five- and ten-year survival rate of 85% and 49%, respectively. However, it is very difficult to predict the clinical behaviour of patients with PC and probably the ultimate prognosis depends on successful resection of the tumour at the initial surgery.

Immunomodulation techniques in a pig-to-rat model of xenoislet transplantation to prolong graft survival.

Pancreas allotransplantation can restore full metabolic control in patients with type I diabetes, but has several limitations. Pancreatic islet xenotransplantation (XiTx) is considered a reliable alternative. The aim of this study was to evaluate the effect of gamma-irradiation and a highly selective inducible nitric oxide synthase inhibitor (AE-ITU) in a model of pig-to-rat XiTx. Thirty-five female rats were made diabetic by intraperitoneal injection of streptozocin. Pig pancreatic islets were obtained by enzymatic digestion followed by purification on Ficoll gradients. Approximately 4000 purified pig islet equivalents were placed under the left kidney capsule of the recipient rats. The rats were observed for 15 days and divided into five Groups (G): GI: controls, diabetic rats with no treatment; G2: XiTx; G3: XiTx after gamma-irradiation (20 Gy); G4: XiTx and administration of AE-ITU; G5: XiTx after gamma-irradiation and AE-ITU. Graft survival was defined as the maintenance of the glucose levels at less than 11 mmol/l and a normal response to i.v. glucose challenge. The graft survivals in Groups 2, 3, 4 and 5 were 4.1 +/- 1.8, 7.6 +/- 2.1, 7.6 +/- 2.4, and 10.9 +/- 2.3 days, respectively. The graft survival of G2 was significantly (p < 0.05) lower than the other groups, and the graft survival of G5 was significantly higher in respect of both G3 and G4 (log-rank test: p = 0.007). In conclusion, the combination of AE-ITU (to reduce the early inflammatory damage) and gamma-irradiation (to reduce the immunogenicity of the islets) may be considered an interesting option to prolong the euglycaemic period after XiTx.

Sentinel Node Biopsy in Early Breast Cancer.

The approach to the axilla is an evolving paradigm, and recognition of the complexity of breast cancer (BC) biology is changing treatment options. The sentinel lymph node biopsy (SLNB) technique is based on the excision and histological examination of the axillary lymph nodes(s), which is assumed to be the first one draining from the primary tumor. SLNB can accurately stage the axilla, and several trials have shown that there are no significant differences in local recurrence and overall survival between patients treated with or without axillary node dissection (ALND) after a negative SLNB. Surgical morbidity was significantly reduced in terms of rates of lymphedema and neuropathy, with reduced hospital stay and better quality of life after the SLNB procedure. ALND can safely be omitted in patients with ≥2 positive nodes who received conservative surgery and radiotherapy, while ALND is still recommended in clinically N1 BCs, in case of ≥3 positive nodes, and when the number of positive nodes would be crucial for the choice of chemotherapy. Micrometastatic disease can be safely managed with SLNB alone, and additional identification of micrometastases with immunohistochemistry does not affect disease-free survival or overall survival. An appropriate management of the axilla is crucial for the outcome of patients with early BC, and SLNB introduction into the clinical practice dramatically changed the surgical treatment, reducing morbidity without decreasing survival. A tailored approach should be suggested in each patient with BC, considering the biology of the tumor rather than nodal involvement.

Factors Affecting Survival in Patients with Lung Metastases from Colorectal Cancer. A Short Meta-analysis.

Liver and pulmonary metastases (PMs) are relatively common in patients with colorectal cancer. The majority of metastases are suitable for surgical resection, and the effectiveness of metastasectomy is usually assessed based on overall survival (OS). Metastasectomy provides a mean 5-year OS rate of approximately 50%, but the results are better in patients with liver metastases compared to those with PMs. Unfortunately, the presence of bilateral or multiple PMs represents a relative contraindication to surgical metastasectomy. Unresectable PMs can be safely treated with percutaneous radiofrequency ablation or radiotherapy, but the reported results vary widely. Several clinical prognostic factors affecting OS after metastasectomy have been reported, such as number of PMs, hilar or mediastinal lymph node involvement, disease-free interval, age and gender, resection margins, size of the metastases, neoadjuvant chemotherapy administration, and histological type of the primary cancer. The accurate evaluation of all clinical prognostic factors, circulating and immunohistochemical markers, and the study of gene mutational status will lead to a more accurate selection of patients scheduled to metastasectomy, with the aim of improving outcome.

Serum Tumor Markers in Stage I-II Breast Cancer.

The prognosis of breast cancer is strongly influenced by the stage of the disease; therefore, it is essential that breast cancer lesions be diagnosed at the earliest stages. There is an urgent need to identify different biomarkers with a high accuracy for the early detection of this cancer to facilitate clinical management of the disease. A wide number of substances named serum tumor markers can be detected in the serum of patients with breast cancer, including tumor-associated proteins, cytokines, stimulating or inhibiting factors, autoantibodies to antigen tumor-associated substances and miRNAs. Despite ASCO and NACB recommendations, the routine use of breast cancer tumor markers by a significant proportion of oncologists is common, particularly after primary treatment of early tumors. The new promising circulating markers are HER2/neu, Trx 1, CSF1, autoantibodies against these tumor-associated antigens, and miRNAs, which are non-coding RNA molecules that regulate the translation of mRNA and control a number of biological processes, including oncogenic cells proliferation. The expression of single miRNA results in a miRNA signature, and is considered a potential biomarker for early breast cancer. However, additional studies are needed to identify its real usefulness.

Adjuvant Treatment of Early Breast Cancer in the Elderly.

Breast cancer is common in the elderly, as more than 50% of these tumors are diagnosed in patients aged 65 years or older. Elderly women may also delay reporting or underreport to their physician suspicious symptoms and lesions, so that breast cancer is more likely to be diagnosed at a more advanced stage, with putatively inferior outcomes. Adjuvant hormonal therapy has clear benefits for all women with hormone receptor-positive early breast cancer, despite the fact that it is still under-prescribed in elderly women, but the benefits of tamoxifen are more evident than that observed in younger patients. Aromatase inhibitors significantly prolong disease-free survival, reducing the risk of metastases and contralateral cancer compared with tamoxifen, and these benefits are greater in women aged ≥65 years. However, in case of a history of pathological fractures, arthritis or chronic musculoskeletal pain syndromes, tamoxifen still represents the preferred adjuvant option. In patients with a high risk of recurrence with hormonal therapy alone, the cardiac toxicity of nonanthracycline regimens should be taken into account. Trastuzumab-based therapy should be offered to most patients with HER2-overexpressing tumors. Older patients have an increased risk of disease recurrence and cancer-related mortality, because they are usually undertreated due to their age and longevity. Thus, a multidisciplinary geriatric approach is required, but the optimal management of these patients is still not well defined.

Advances in the Treatment of Triple-negative Early Breast Cancer.

Triple-negative breast cancer represents approximately 10-20% of all breast cancers and is associated with worse prognosis than other subtypes, with a higher risk of recurrence and death than other breast cancer types. This cancer is considered a heterogeneous disease comprising a spectrum of cancers with distinct activated biological pathways, various levels of chemosensitivity and different propensity for metastasis. Currently, chemotherapy represents the mainstay of medical treatment of these patients, because of the absence of well-defined molecular target agent, and we cannot use investigational classifications to determine appropriate systemic therapy outside of clinical trials. The specific adjuvant chemotherapy that may be most effective is still being determined but there is general consensus that regimens containing anthracyclines and taxanes are the standard approach for patient after surgery. Unfortunately, although some patients respond to treatment, other women have a high degree of intrinsic resistance to the same therapy. Moreover, in some studies, the pathological complete response was significantly higher in women treated with platinum-based regimen with respect to those treated with other chemotherapy regimen. The systematic evaluation of the predictive value of genomic alterations is critically important for a better comprehension of this entity and to develop new effective therapeutic strategies. In the future, a personalized therapeutic approach based on biology-oriented characteristics and molecular profiling may be effective for the patients.

Adjuvant Hormonal Therapy in Women with Early-stage Breast Cancer.

For decades, adjuvant hormonal therapy has become the standard treatment of patients with estrogen receptor-positive breast cancer. Currently, the drugs available are GnRH agonists, selective estrogen receptor modulators, and aromatase inhibitors. The use of GnRH agonists represents a potentially reversible treatment that can restore ovarian function after chemotherapy. In premenopausal women, systemic therapy based on selective estrogen receptor modulators administration (e.g., tamoxifen) usually represents the standard adjuvant treatment. There are not sufficient data to recommend the routine addition of GnRH agonists to other endocrine therapies. In postmenopausal women, the disease-free survival was significantly prolonged in patients treated with aromatase inhibitor compared with those treated with tamoxifen, but the survival benefit was modest. Better results were obtained when the two drugs were administered sequentially. According to the ASCO guidelines, after 5 years of tamoxifen treatment, either tamoxifen or aromatase inhibitors therapy should be suggested for an additional 5 years. Unfortunately, most adverse events are consistent with estrogen deprivation and are common to all therapies, and the cumulative toxicity causes discontinuation and nonadherence to therapy in up to 50% of patients. Switching tamoxifen to an aromatase inhibitor may reduce adverse event incidence. Molecular-targeted therapy is useful in patients with advanced, relapsed or hormonal therapy-resistant tumors, usually as second- or third-line treatment. These drugs are usually added to aromatase inhibitors; however, currently, they have not yet been used in patients with early breast cancer.