DWI may identify biological heterogeneity of breast neoplasms. • ADC values vary significantly according to biological features of breast cancer. • Compared with other types, HER2-enriched tumours show highest median ADC value. • Knowledge of biological heterogeneity of breast neoplasm may improve imaging interpretation.

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first-and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3.5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.

Summary. About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2±67) not responding to a ®rst course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3´5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 mg/kg subcutaneously from day 1 to 90). The median interval between ®rst and second treatment was 151 d (range 58±361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, de®ned as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14±377). Nine patients (30%) achieved complete remission (neutrophils >2´0´10 9 /l, haemoglobin >11 g/dl and platelets >100´10 9 /l). The overall survival rate was 93% with a median follow-up of 914 d (range 121±2278). So far, no patient has relapsed. Female gender was signi®cantly associated with a poorer likelihood to respond (P 0´0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to ®rst-line IS treatment.

Breast cancer is the most frequent cancer in women: in 2018, almost two million cases have been diagnosed all over the world and it represents the principal cause of death from a neoplastic disease in women. In the past years, breast cancer prognosis has significantly improved over time: currently 5-year survival rates are in the range of 90%, and 10-year survival is about 80%. This improvement has been mostly observed in western countries, due to high coverage and compliance with screening programs, leading to early diagnosis, i.e., when the disease is at a subclinical level, and to an improvement in tumor molecular characterization and innovative systemic treatments. Yet the identification of different biological breast cancer subtypes prompted the development of innovative targeted agents and improved treatment personalization. On the other hand, longer survival rates and increasing proportions of cured patients require dedicated strategies to manage long-term sequelae of breast cancer treatments, with particular attention to quality of life. This review analyzes the most important issues, potentially occurring with cancer treatments, concerning long-term sequelae and quality of life, to define a global approach to breast cancer survivorship.