Efficacy of extended aromatase inhibitors for hormone-receptor-positive breast cancer: A literature-based meta-analysis of randomized trials.

BACKGROUND: Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS). METHODS: A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement. RESULTS: The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68-0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87-1.12; P = 0.84). CONCLUSION: This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.

[Fatigue at various muscular lengths in myotonic dystrophy]. / La fatica a diversa lunghezza muscolare nella distrofia miotonica.

In myotonic dystrophy alteration in membrane excitability characterizes, in addition to the dystrophic process, modifications of contractile function detectable after fatigue. To verify in which extent sarcolemmal activation or contractility mechanisms are involved in fatigue, some electrophysiological and dynamometer parameters have been studied in tibialis anterior of 5 myotonic dystrophy patients. Evaluation has been performed basally and after protocol consisting of intermittent isometric voluntary contractions lasting 15', at two different muscle lengths, optimal and short. Administration at several recovery times of 20 and 50 Hz tetanizing sequences shows how processes distal to membrane excitability are mainly responsible for fatigue at optimal length, while relative potentiation of excitability preserves the muscle from excessive force loss at short length.

[Changes in muscular excitability and contractility caused by fatigue in Steinert's disease]. / Modificazioni dell'eccitabilità e della contrattilità muscolari indotte dalla fatica nella malattia di Steinert.

To study effects of fatigue on muscle excitability and contractility in myotonic dystrophy (MyD), we evaluated, by ulnar nerve supramaximal stimulation, both single shock and 40 Hz tetanus, M wave and force parameters from adductor pollicis. In 8 MyD patients and in 6 controls amplitude of M wave, electromechanical delay, single twitch and tetanus tension, contraction and half-relaxation times were recorded in basal condition and at different times after 75 sec. of maximal voluntary contraction. Reduction of force related to fatigue was per cent lesser in MyD compared to controls. Electro-mechanical delay, basally longer in MyD, showed after fatigue 15% increment compared to 47% in controls. Half-relaxation time increased in both groups, but in MyD recovery was faster. Peculiar alterations of excitation-contraction coupling and contractility occurring in MyD can explain the observed modifications of fatigue phenomena in this disease.