Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated.

MRgFUS is an encouraging mini-invasive treatment for adenomyosis that permits to maintain the integrity of the uterus in a pathology with limited therapeutic possibility.

Objective: To demonstrate the efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in uterine fibroid treatment in terms of extension of non-perfused volume and improvement of the symptoms above all in fertile women. This method is a valid alternative to hysterectomy. Materials and Methods: From October 2011 to September 2015, 78 patients, aged between 23 and 51 years, affected by uterine fibroids, were treated with MRgFUS in the present department. The authors included 47 patients affected only by uterine fibroids (size range 2-14 cm) and 31 affected by multiple fibroids. Symptoms were dysmenorrhea, menorrhagia, and infertility. Symptomatology was assessed through the symptoms severity score questionnaire. The authors evaluated the radicalization of the treatment measuring the non-perfused volume (NPV) on the c.e. T1-weighed sequences immediately after the treatment and compared these results with the pre-treatment volume of the fibroids. A dedicated informatics measurement system was used. Results: The present results showed a mean of non-perfused volume of 78%, with a good radicalization of the treatment. Patients presented a marked reduction of symptoms (90%) when compared to pre-treatment. Conclusion: The treatment of uterine fibroids using MRgFUS is a valid alternative to surgery. A good extension of the necrotic area is obtained in women affected by multiple and single fibroids, maintaining the integrity of the uterus.

Background: Patients affected by uterine fibroids were evaluated to define inclusion and exclusion criteria for treatment with Magnetic Resonance-guided Focus Ultrasound Surgery (MRgFUS), the non-invasive technique considered as an efficient alternative to hysterectomy and myomectomy. Methods: From October 2011 to December 2015, 174 patients aged from 23 to 51 years, affected by uterine fibroids (size ranging from 2 to 14 cm) were evaluated in our clinical unit, to define candidature for MRgFUS treatment. Symptomatic patients were submitted to preliminary MRI. The severity of symptoms was evaluated with the UFS-QOL questionnaire. All patients were clinically examined to verify the absence of all conditions reported by the exclusion criteria grid. Results: 54 out of 174 patients were considered suitable for MRgFUS and treated; in 16 out of 174 patients, suitable for MRgFUS, treatment was declined because MRI evaluation, performed on the treatment's day, showed interposition of bowel and/or bladder. 104 out of 174 were not candidate to MRgFUS, due to interposition of bowel and bladder (46/104), presence of pedunculated fibroids (18/104), large abdominal scars (18/104), close proximity to the spine and nerve roots (22/104). Conclusions: In our study, applying the inclusion and exclusion criteria, the percentage of treatable and treated patients was 40% and 31%, respectively. Diriment in the choice of MRgFUS over myomectomy is the possibility to achieve the same result (disappearance or marked reduction of the fibroid) without risks and complications related to conventional surgery. Furthermore, hospitalization times are sensibly reduced to one day only and the convalescence is maximum 2-3 days.