A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) ± target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making.

Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m². Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms.

A total of 3,324 singleton pregnant women were screened for pre-term delivery and 128 women were finally randomised and analysed for outcome showing borderline cervical length (25–29 mm) and elevated cervico-vaginal interleukin 6 levels. To verify if vaginal administration of lactoferrin might have an influence on these variables, two groups of 64 patients were formed. Study cases were submitted to lactoferrin for 21 days; controls received no treatment. An inverse relation was found between interleukin 6 levels and cervical length. On day 30 from the beginning of the treatment, study cases showed a decrease in interleukin 6 levels and an increase in cervical length. A greater number of women with regular uterine contractions and reduced cervical consistency before the 37th week of gestation were found in the controls. Our data show that lactoferrin could play a role in reducing the number of women at risk for pre-term birth for shortened cervical length and elevated interleukin 6 levels.

The aim of this study was, firstly, to analyze the histopathological characteristics of placentas in women with uneventful pregnancies and affected by COVID-19 at the time of delivery; and secondly, to correlate histological findings to maternal and neonatal characteristics. In our single-center prospective observational study, 46 placentas from term uncomplicated singleton pregnancies of patients with a documented SARS-CoV-2 infection at the time of delivery underwent histological examination. Despite a normal feto-maternal outcome, most of the placentas (82.6%) presented signs of maternal vascular malperfusion, while features of fetal vascular malperfusion were found in 54% of cases. No correlation was detected between maternal and neonatal characteristics and the severity of blood circulation disease, and abnormal findings were also described in asymptomatic patients. Moreover, we did not find any maternal symptoms or clinical details allowing for the prediction of abnormal placental findings in pregnancy complicated by COVID-19 infection. Our results suggest that SARS-CoV-2 infection during pregnancy could lead to acute placental dysfunction.

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Preterm labor is a public health problem and to this day, it's the great challenge of modern obstetrics. We conducted a randomized double-blind controlled study. At the admission, all patients were submitted to cardiotocography. Patients with regular contractions but without decreasing of cervical length or funneling at transvaginal sonography were admitted. 90 patients at 24-34 weeks of gestation were finally recruited. Patients were randomly divided in two groups: A group (45 patients) received a single transvaginal dose of docosahexaenoic acid (1 gr of DHA); B group (45 patients) received placebo. At 120 minutes, cardiotocographic examination was performed in all patients. A group showed a significant decrease in number and intensity of contractions (p<0.05) as compared to B group. The results of our study show that vaginally administered DHA during pregnancy is effective on uterine contractions providing a significant decrease of spontaneous contractions and probably reducing the risk of preterm delivery.