Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer.

Importance: Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date. Objectives: To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM. Design, Setting, and Participants: For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022. Exposure: Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy. Main Outcomes and Measures: VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points. Results: Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression. Conclusions and Relevance: The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.

Stability of circulating miRNA in saliva: The influence of sample associated pre-analytical variables.

BACKGROUND AND AIMS: Increasing evidence supports the practicability of salivary cell-free (cf) miRNA as liquid biopsy markers in cancers. Its successful translation in the clinical setting requires reproducible approaches for saliva manipulation, in order to control for pre-analytical variables influencing miRNA stability. This study aims to define the optimal conditions to maintain the integrity of saliva during collection, transport and processing with respect to cf-miRNA quantification. MATERIALS AND METHODS: Saliva was collected from 20 healthy subjects and 8 oral cancer patients. Two sampling methods were tested and different storage temperatures and times were evaluated. Salivary expression level of target miRNAs was quantified by qPCR. Comparison between group mean values at specific conditions were performed using paired t-tests. Agreement between measurements was evaluated using a Bland-Altman plot. RESULTS: Different collection methods revealed comparable levels of salivary miR-484 and miR-106b-5p in both subject cohorts. MiRNAs were stable for up to 48 h at 4 °C in saliva supernatant, showing significant alteration after 96 h. Mid-term storage of supernatant at -20 °C decreased miRNA stability significantly compared to standard -80 °C. CONCLUSIONS: Cf-miRNA in saliva were slightly altered by collection methods and storage conditions, both in healthy and in pathological contexts, and remained stable for a period of time compatible with main clinical routine needs.

Molecular Basis and Rationale for the Use of Targeted Agents and Immunotherapy in Sinonasal Cancers.

Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types.