The optimal timing between neoadjuvant therapy and surgery of breast cancer: A brief systematic review of the literature.

Neoadjuvant therapy is a cornerstone of some early and locally advanced breast cancer treatment. The use of neoadjuvant chemotherapy, in fact, allows to obtain numerous advantages, including allowing a more conservative intervention, evaluating the in vivo response to therapy, modulating the intensity of subsequent treatments based on the degree of response to therapy and allowing to surgery with information on genetics. However, at the end of neoadjuvant cytotoxic therapy it is not possible to carry out surgery immediately, as a certain amount of time is required for recovery from toxicity, especially haematological, due to the systemic therapy itself. At the same time, it is intuitive that too much time must not pass between the end of neoadjuvant therapy and surgery. The goal of this systematic literature review is to summarize the most relevant literature data on this topic, selected and extracted according to the methodology of systematic reviews.

Molecular Analysis of Luminal Androgen Receptor Reveals Activated Pathways and Potential Therapeutic Targets in Breast Cancer.

BACKGROUND/AIM: Triple-negative breast cancers represent 15% of all mammary malignancies and encompass several entities with different genomic characteristics. Among these, luminal androgen receptor (LAR) tumors express the androgen receptor (AR) and are characterized by a genomic profile which resembles luminal breast cancers. Moreover, LAR malignancies are usually enriched in PIK3CA, KMTC, CDH, NF1, and AKT1 alterations. Still, molecular features, clinical behavior and prognosis of this variant remain controversial, while identification of effective treatments represents an unmet medical need. Additionally, the predictive role of the AR is unclear. MATERIALS AND METHODS: We performed an extensive next generation sequencing analysis using a commercially available panel in a cohort of patients with LAR breast cancer followed at two local Institutions. We next employed bioinformatic tools to identify signaling pathways involved in LAR pathogenesis and looked for potentially targetable alterations. RESULTS: Eight patients were included in the study. In our cohort we found 26 known genetic alterations (KGAs) in 15 genes and 64 variants of unknown significance (VUS) in 59 genes. The most frequent KGAs were single nucleotide variants in PIK3CA, HER2, PTEN and TP53. Among VUS, CBFB, EP300, GRP124, MAP3K1, RANBP2 and TSC2 represented recurrently altered genes. We identified five signaling pathways (MAPK, PI3K/AKT, TP53, apoptosis and angiogenesis) involved in the pathogenesis of LAR breast cancer. Several alterations, including those in PIK3CA, ERBB2 and PI3K/AKT/mTOR signaling, were potentially targetable. CONCLUSION: Our findings confirm a role for PI3K/AKT/mTOR signaling in the pathogenesis of LAR breast cancers and indicate that targeting this pathway, along with ERBB2 mutations, may represent an additional therapeutic strategy which deserves further exploration in larger studies.

Mutational Analysis of BRCA1 and BRCA2 Genes in Breast Cancer Patients from Eastern Sicily.

Purpose: Germline mutations of BRCA1 and BRCA2 are associated with a defined lifetime risk of breast (BC), ovarian (OC) and other cancers. Testing BRCA genes is pivotal to assess individual risk, but also to pursue preventive approaches in healthy carriers and tailored treatments in tumor patients. The prevalence of BRCA1 and BRCA2 alterations varies broadly across different geographic regions and, despite data about BRCA pathogenic variants among Sicilian families exist, studies specifically addressing eastern Sicily population are lacking. The aim of our study was to investigate the incidence and distribution of BRCA pathogenic germline alterations in a cohort of BC patients from eastern Sicily and to evaluate their associations with specific BC features. Patients and Methods: Mutational status was assessed in a cohort of 389 BC patients, using next generation sequencing. The presence of alterations was correlated with tumor grading and proliferation index. Results: Overall, 35 patients (9%) harbored a BRCA pathogenic variant, 17 (49%) in BRCA1 and 18 (51%) in BRCA2. BRCA1 alterations were prevalent among triple negative BC patients, whereas BRCA2 mutations were more common in subjects with luminal B BC. Tumor grading and proliferation index were both significantly higher among subjects with BRCA1 variants compared to non-carriers. Conclusion: Our findings provide an overview about BRCA mutational status among BC patients from eastern Sicily and confirm the role of NGS analysis to identify hereditary BC patients. Overall, these data are consistent with previous evidences supporting BRCA screening to properly prevent and treat cancer among mutation carriers.

Next generation sequencing in a cohort of patients with rare sarcoma histotypes: A single institution experience.

Sarcomas are mesenchymal-derived cancers with overlapping clinical and pathologic features and a remarkable histological heterogeneity. While a precise diagnosis is often challenging to achieve, systemic treatment of sarcomas is still quite uniform. In this scenario, next generation sequencing (NGS) may be exploited to assist diagnosis and to identify specific targetable alterations. However, the precise role of genomic characterization in these diseases is still debated. In the present study, we analyzed 18 samples from 11 low-incidence sarcomas using NGS technology. We also used an in-silico prediction tool to reclassify variants of unknown significance and then looked for potentially druggable alterations to match with targeted therapies. Our cohort presented several predictable findings (e.g. MYC amplification in radio-induced angio-sarcoma, COL1A1-PDGFB rearrangements in dermatofibrosarcoma protuberans) along with unexpected results (e.g. the reciprocal WT1-EWSR1 fusion in a desmoplastic small round cell tumor). One third of patients (6/18) displayed at least one actionable molecular alterations. Our experience confirms the potential role of NGS in the management of rare sarcomas. This tool may support the diagnostic process, but also detect targets for personalized therapies.

Total mesorectal excision laparoscopic versus transanal approach for rectal cancer: A systematic review and meta-analysis.

INTRODUCTION: Total mesorectal excision (TME) performed for the first time by Held through an open approach, it has become the standard technique for the surgical treatment of rectal cancer. The aim the of this meta-analysis is to compare the outcomes provided by TaTME than LaTME. MATERIAL AND METHODS: In this meta-analysis, we included all comparative studies, prospective and retrospective, which addressed in low and middle rectal cancer, a comparison between TaTME and LaTME. A search was performed through MEDLINE and Cochrane Database. 846 records were identified. RESULTS: Eight relevant studies have been included in this meta-analysis. The studies were from France, Russia, USA, Netherlands, Taiwan, Egypt. The eight studies including 471 patients with middle or low rectal cancer. CONCLUSION: The meta-analysis confirmed safety of TaTME for low and middle rectal cancer. TaTME can lead to a high quality of rectal cancer resection specimen.

Early Gastrointestinal Progression to Immunotherapy in Lung Cancer: A Report of Two Cases.

Intestinal and pancreatic metastases are rare and often challenging to recognize and manage. Lung cancer patients with enteric involvement usually display poor outcomes. Hyperprogression to immunotherapy represents a concern, even though there is currently no agreement on its exact definition. Gastrointestinal hyperprogression to immune checkpoint inhibitors has not been described so far. In these cases, distinguishing disease-related symptoms from immune-related adverse events may represent a diagnostic conundrum. Here, we report two cases of non-small-cell lung cancer experiencing a rapid pancreatic and colic progression to immunotherapy, respectively. While further investigations to identify biomarkers associated with hyperprogression are warranted, clinicians should be aware of the potential unusual clinical presentations of this phenomenon.