Liquid biopsy (LB) involves the analysis of circulating tumour-derived DNA (ctDNA), providing a minimally invasive method for gathering both quantitative and qualitative information. Genomic analysis of ctDNA through next-generation sequencing (NGS) enables comprehensive genetic profiling of tumours, including non-driver alterations that offer prognostic insights. LB can be applied in both early-stage disease settings, for the diagnosis and monitoring of minimal residual disease (MRD), and advanced disease settings, for monitoring treatment response and understanding the mechanisms behind disease progression and tumour heterogeneity. Currently, LB has limited use in clinical practice, primarily due to its significant costs, limited diagnostic yield, and uncertain prognostic role. The application of artificial intelligence (AI) in the medical field is a promising approach to processing extensive information and applying it to individual cases to enhance therapeutic decision-making and refine risk assessment.

Background: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptorpositive disease and therefore candidate for adjuvant endocrine therapy (ET). Patients and methods: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. Results: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9% of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5% of cases. Conclusions: AI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.

Adjuvant abemaciclib + endocrine therapy (ET) improves long-term outcomes in high-risk, hormone receptor–positive (HR+)/HER2-negative early breast cancer (eBC). However, treatment is frequently complicated by diarrhea, affecting adherence and quality-of-life (QoL). Increasing evidence suggests that abemaciclib-induced gastrointestinal toxicity may involve gut microbiota alterations. We conducted a prospective case-control pilot study evaluating the efficacy of MBR-01, a standardized prebiotic/probiotic formulation, in mitigating abemaciclib-induced diarrhea. We enrolled 20 postmenopausal patients with high-risk HR+/HER2-negative eBC considered unfit for adjuvant chemotherapy. Patients received abemaciclib + letrozole (control, n = 10) or abemaciclib + letrozole + MBR-01 (experimental, n = 10). The primary endpoint was the incidence and severity of diarrhea; secondary endpoints included treatment adherence, QoL assessments and exploratory baseline/week-12 microbiota characterization according to treatment arm. Trial registration number: ISRCTN11948182. Diarrhea occurred in all patients. In the control group, diarrhea was predominantly grade 1 (50%) or grade 2 (40%), with one grade 3 event (10%). In the MBR-01 group, diarrhea frequency and severity were reduced by ∼70% at the end of week-12; 90% of patients experienced only grade 1 diarrhea or none by week-12, and no grade ≥3 events. Dose modification was only required in one control. Decrease in alpha-diversity and F.prausnitzii were associated with earlier diarrhea onset and longer duration; increase in E.coli correlated with higher grade events. MBR-01 supplementation seemed to preserve microbial diversity and limited E.coli expansion. QoL was significantly improved with MBR-01. MBR-01 may effectively mitigate abemaciclib-induced diarrhea, likely through the achievement of stabilization of gut microbiota composition. Larger prospective studies are warranted to validate these preliminary findings.