Association of SULT1A1 Arg²¹³His polymorphism with male breast cancer risk: results from a multicenter study in Italy.

Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg(213)His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg(213)His could exert an effect on MBC development. The primary aim of this study was to evaluate the influence of the SULT1A1 Arg(213)His polymorphism on MBC risk. The secondary aim was to investigate possible associations with relevant clinical-pathologic features of MBC. A total of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1 Arg(213)His polymorphism by PCR-RFLP and high-resolution melting analysis. All MBC cases were characterized for relevant clinical-pathologic features. A significant difference in the distribution of SULT1A1 Arg(213)His genotypes was found between MBC cases and controls (P < 0.0001). The analysis of genotype-specific risk showed a significant increased MBC risk in individuals with G/A (OR 1.97, 95% CI 1.50-2.59; P < 0.0001) and A/A (OR 3.09, 95% CI 1.83-5.23; P < 0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A significant association between SULT1A1 risk genotypes and HER2 status emerged. Results indicate that SULT1A1 Arg(213)His may act as a low-penetrance risk allele for developing MBC and could be associated with a specific tumor subtype associated with HER2 overexpression.

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy.

It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common low-penetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 age-matched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43-2.05; p = 0.0001), rs3803662/TOX3 (OR = 1.59; 95 % CI: 1.32-1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05-1.50; p = 0.013). Furthermore, we showed that the prevalence of the risk genotypes of ESR1 tended to be higher in ER- tumors (p = 0.062). In a case-case multivariate analysis, a statistically significant association between ESR1 and ER- tumors was found (OR = 1.88; 95 % CI: 1.03-3.49; p = 0.039). Overall, our data, based on a large and well-characterized MBC series, support the hypothesis that common low-penetrance BC susceptibility alleles play a role in MBC susceptibility and, interestingly, indicate that ESR1 is associated with a distinct tumor subtype defined by ER-negative status.

[Effectiveness of nasal positive pressure ventilation in the management of acute refractory left ventricular insufficiency]. / Utilità ed efficacia della ventilazione a pressione positiva con maschera nasale nel trattamento dell'insufficienza ventricolare sinistra acuta refrattaria.

BACKGROUND: Ehen refractory to optimal medical treatment cardiogenic pulmonary edema requires mechanical ventilation as a last therapeutic resource. In recent years an increasing number of authors reported their experience in the management of acute or subacute respiratory failure with non-invasive mechanical ventilation by nasal mask. MATERIALS AND METHODS: Encouraged by the first promising results reported in literature we experimented this new therapeutic tool in a first group of seven elderly patients (mean age: 76.57--range: 65-89); they all had been admitted for severe cardiogenic pulmonary edema unresponsive to maximal doses of the conventional drugs available for treating acute decompensated heart failure. The enrolled patients were treated with intermittent ventilation administered by nasal mask at selected values of inspiratory positive airway pressure (IPAP) that were comprised between 10 and 20 cm H2O. At the same time an expiratory positive airway pressure (EPAP) at values comprised between 3 and 8 cm H2O was applied. Ventilation was continued for variable periods of 3-24 hours until acceptable values of PaO2 and PaCO2 were obtained. The ventilation modality was spontaneous, spontaneous-time or timed depending on the patients' level of consciousness at starting time. RESULTS: A good short-term outcome was achieved in all the patients regardless of the ventilation modality applied. The main blood gas alteration was severe hypercapnia with acidosis in three patients, while the other four presented critical hypoxemia unresponsive to simple oxygen supply even if delivered by high-flow Venturi mask. Four of our seven patients were discharged from hospital in satisfactory haemodynamic conditions; the remaining three died during hospitalization from refractory heart failure. CONCLUSIONS: In this our preliminary experience the therapeutic approach with nasal positive pressure ventilation (NPPV) and EPAP proved to be very effective to improve the signs and symptoms of acute refractory cardiogenic pulmonary edema as it avoided the need of invasive mechanical ventilation. It was well tolerated by all our patients; besides it was not difficult to use or time-consuming for physician and nurses. On the other hand it didn't modify our patients' medium or long-time prognosis which was strictly related to their preexisting left ventricular pump derangement.

[Recovery of pump function in ischemic hypokinetic cardiopathy subjects treated with weekly intermittent infusion of dobutamine. A clinical case]. / Recupero della funzione di pompa in soggetto con cardiopatia ipocinetica ischemica trattata con dobutamina in infusione intermittente settimanale. Un caso clinico.

The case is reported of a 69-year-old man with refractory heart failure due to ischemic cardiomyopathy. All other available treatments having failed and 250 mg doses of furosemide having been administered without success, dobutamine infusion was tried, at first with 72 hours of continuous infusion of 5 mcg/kg/min, followed by intermittent infusion at the same dosage, first with 12-h intervals, subsequently at the rate of 2-3 infusions weekly, and finally, after about 50 days, with a single weekly infusion. Clinical and hemodynamic results were brilliant with the patient passing from grade IV NYHA to grade II and from ejection fraction 21% (Teichholz M-mode measurement) to 55%, 14 months after the start of dobutamine treatment. Discussing the possible mechanisms of this favourable result, the authors stress the possible improvement of the contractility of the "stunned" or "hibernating" myocardial segments. On the basis of their experience and of data in the literature the authors underline the validity of a therapeutic protocol of intermittent dobutamine infusion for severe heart failure.