The evidence supporting the use of trastuzumab (T) in a metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first-line therapy for metastatic breast cancer (mBC) in women previously treated with T in the adjuvant setting.
Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ?70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.
Indication for the use of trastuzumab was given in Italy in 2000 for the treatment of HER-2 metastatic breast cancer and in 2006 for early stage breast cancer. Information on trastuzumab use and on its possible variation with age in Italy is however limited. Using health care administrative databases, we evaluated the prevalence of the use of trastuzumab, and the probability for administration since the first hospitalization for breast cancer in various age groups, in two series of Italian women diagnosed with breast cancer in the Lombardy region (2004-2009) and in the Palermo district. The ratio between trastuzumb users and patients with a hospitalization for breast cancer increased from 2.9% in 2004 up to 17.2% in 2009 in Lombardy. Patients aged <65 years were more frequent users (9.6%) compared to those aged ? 75 years (1.3%). Similarly, in the Palermo district the ratio increased from 10.6% in 2006 to 28.5% in 2008, with subjects aged <65 years more frequently using trastuzumab (19.1%), than subjects aged ? 75 years (6.2%). The age ratio between younger and older patients decreased over time in both settings (from 15 in 2004 to 10.2 in 2006, and 5.2 in 2009 in Lombardy, and from 4.0 in 2006 to 2.3 in 2009 in the Palermo district). The proportion of breast cancer patients using trastuzumab increased over time both in Lombardy and in Palermo district, though geographical differences persisted. Younger breast cancers patients were more likely to receive a trastuzumab treatment than elderly ones, but the difference declined over calendar period.
Most studies investigating the reasons for smoking initiation are based on adolescents or young individuals. We considered the issue in a large dataset on the general Italian population. Six population-based surveys on smoking were conducted annually from 2005 to 2010 on representative samples of Italian individuals aged 15 years or over, involving more than 3000 individuals each year. A specific question on the main reason to start smoking was asked to 7469 ever smokers. Overall, 59.9% of ever smokers started smoking before 18 years of age and 33.6% started smoking before 16 years of age. Among ever smokers, 61.1% reported having started smoking because of the influence of friends, 15.6% for enjoyment and satisfaction, 9.0% to feel mature and independent, 6.6% because of the influence of partner/family, 2.5% because of stress, 1.9% to feel more secure and 1.8% for curiosity. The finding that the majority of Italian men and women - particularly those who started smoking at a young age - started smoking because of the influence of friends suggests that antismoking campaigns should consider social influence, resistance and the dimension of self-esteem. An improvement in the legislation prohibiting the purchase of tobacco products by minors aged less than 18 years and a smoking ban in school courtyards are urgently required in Italy.
Scarce information is available, particularly from Europe, on why smokers quit. We analyzed this issue in a large dataset of Italian ex-smokers. Six population-based surveys on smoking were annually conducted in 2005-2010 on a representative sample of the Italian adult population, which included more than 3000 participants each year. A specific question on the main reason for quitting smoking was answered by a total of 3075 ex-smokers (1936 men and 1139 women). Overall, 43.2% of ex-smokers mentioned a current health condition as the main reason to stop smoking, 31.9% stopped to avoid future health problems, 6.3% stopped because of pregnancy or child birth, 4.0% because of imposition by the partner/family, 3.7% because of a physicians recommendation, 3.0% because of the economic cost, 0.5% because of smoking bans, and 4.6% because of other reasons. Statistically significant differences in the motivation to quit smoking have been found according to sex, age, social class, and smoking history. The majority of ex-smokers quit because of tobacco-related health conditions. Only a minority of ex-smokers quit to avoid future illness. Physicians should be encouraged to assist smokers to quit. The current prices of cigarettes in Italy are not sufficiently high to discourage people from continuing smoking.
The design of an electromagnet requires the compliance with a number of constraints such as power supply characteristics, coil inductance and resistance, and, above all, heat dissipation, which poses the limit to the maximum achievable magnetic field. A common solution consists in using copper tubes in which a coolant flows. This approach, however, introduces further hydrodynamic concerns. To overcome these difficulties, we developed a new kind of electromagnet in which the pipe concept is replaced by a duct formed by the windings. Here we report on the realization and characterization of a compact model system in which the conductors carry a current that is one order of magnitude higher than the current allowable with conventional designs.
Concerns have been raised about the cardiac safety profile of trastuzumab for the adjuvant treatment of early stage breast cancer in clinical practice. We assessed trastuzumab-related cardiotoxicity and its predictors in a large cohort of Italian women.
The aim of this study was to describe the clinical use of bevacizumab in Lombardy (9.5 million inhabitants), Italy, during 2006-2007 in patients with metastatic colorectal cancer (mCRC) to evaluate compliance with the Italian Medicine Agency (AIFA) indications, the incidence of adverse events, and the survival rate. We performed computerized record linkage among three different Lombardy health care databases: File F registry, Regional discharge database, and Registry Office records. Patients were classified into approved and off-label uses according to the AIFA indications. Treatment with bevacizumab was administered to 780 patients, of whom 81.7% (n = 637) had mCRC. Among these, 37.8% (n = 241) of patients received the drug in observance of AIFA indications. Overall, ?10% of patients had serious treatment-related toxicities (fistula, 3.5%; venous thromboembolism, 2.8%; hemorrhage, 1.9%; intestinal perforation and arterial thromboembolism, <1%). The 1-year survival rate was 74.3% and the 2-year survival rate was 39.2%. The median survival time was 20.5 months, and there were no meaningful differences between gender and age groups. There was a gap between the bevacizumab approved indication and clinical practice pattern: overall, less than one half of the patients received bevacizumab in observance with the regulatory indication. The main reason for nonadherence to the indication was use as a second-line or advanced line of therapy. The incidence of serious adverse events and the survival rates of mCRC patients were similar to those reported in clinical trials.
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