SAMHD1 expression is a surrogate marker of immune infiltration and determines prognosis after neoadjuvant chemotherapy in early breast cancer.

PURPOSE: The lack of validated surrogate biomarkers is still an unmet clinical need in the management of early breast cancer cases that do not achieve complete pathological response after neoadjuvant chemotherapy (NACT). Here, we describe and validate the use of SAMHD1 expression as a prognostic biomarker in residual disease in vivo and in vitro. METHODS: SAMHD1 expression was evaluated in a clinical cohort of early breast cancer patients with stage II-III treated with NACT. Heterotypic 3D cultures including tumor and immune cells were used to investigate the molecular mechanisms responsible of SAMHD1 depletion through whole transcriptomic profiling, immune infiltration capacity and subsequent delineation of dysregulated immune signaling pathways. RESULTS: SAMHD1 expression was associated to increased risk of recurrence and higher Ki67 levels in post-NACT tumor biopsies of breast cancer patients with residual disease. Survival analysis showed that SAMHD1-expressing tumors presented shorter time-to-progression and overall survival than SAMHD1 negative cases, suggesting that SAMHD1 expression is a relevant prognostic factor in breast cancer. Whole-transcriptomic profiling of SAMHD1-depleted tumors identified downregulation of IL-12 signaling pathway as the molecular mechanism determining breast cancer prognosis. The reduced interleukin signaling upon SAMHD1 depletion induced changes in immune cell infiltration capacity in 3D heterotypic in vitro culture models, confirming the role of the SAMHD1 as a regulator of breast cancer prognosis through the induction of changes in immune response and tumor microenvironment. CONCLUSION: SAMHD1 expression is a novel prognostic biomarker in early breast cancer that impacts immune-mediated signaling and differentially regulates inflammatory intra-tumoral response.

The impact of pleural disease on the management of advanced ovarian cancer.

Malignant pleural effusion is the most common site of stage IV ovarian cancer. A positive cytology is required for a stage IVA diagnosis. Unfortunately, the accuracy rate of pleural cytology remains low. A number of factors have been identified as prognostic for clinical outcomes in patients with epithelial ovarian cancer (EOC), the International Federation of Gynaecology and Obstetrics (FIGO) stage and residual tumor after debulking surgery being the most widely reported. Thereby careful selection of patients is crucially important, yet no preoperative predictor has proven sufficiently reliable to predict surgical outcome. The authors present a review of the literature on stage IV ovarian cancer specifically focusing on prognostic value of FIGO stage, preoperative workup, role of video-assisted thoracic surgery and maximal cytoreductive surgery.