Peritoneal chemotherapy delivery systems for ovarian cancer treatment: systematic review of animal models.

Introduction: Intraperitoneal chemotherapy for ovarian cancer treatment has controversial benefits as most methodologies are associated with significant morbidity. We carried out a systematic review to compare tumor response, measured by tumor weight and volume, between intraperitoneal chemotherapy delivered via drug delivery systems (DDSs) and free intraperitoneal chemotherapy in animal models of ovarian cancer. The secondary aim was to assess the toxicity of DDS-delivered chemotherapy, based on changes in animal body weight.

Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects.

Purpose: Despite the success of immune checkpoint inhibitors (ICI) across various cancers, their efficacy in metastatic castration-resistant prostate cancer (mCRPC) is modest, except for a subset of patients who experience significant, yet unpredictable, benefits. DNA repair defects (DRD) are associated with higher neoantigen load, which may predict response. Our study explored the potential of DRD for enhanced responsiveness to the ICI nivolumab.

Custom target-sequencing in triple-negative and luminal breast cancer from young Brazilian patients.

Objectives: To identify somatic mutations in tumors from young women with triple-negative or luminal breast cancer, through targeted sequencing and to explore the cancer driver potential of these gene variants.

Methods: A customized gene panel was assembled based on data from previous sequencing studies of breast cancer from young women. Triple-negative and luminal tumors and paired blood samples from young breast cancer patients were sequenced, and identified gene variants were searched for their driver potential, in databases and literature.

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Genetic diversity of germline variants in breast cancer (BC) predisposition genes is unexplored in miscegenated populations, such those living in Latin America. We evaluated 1663 Brazilian BC patients, who underwent hereditary multigene panel testing (20-38 cancer susceptibility genes), to determine the spectrum and prevalence of pathogenic/likely pathogenic (P/LP) variants and variants of uncertain significance (VUS). Associations between P/LP variants and BC risk were estimated in a case-control analysis of BC patients and 18,919 Brazilian reference controls (RC).

Value of the loss of heterozygosity to BRCA1 variant classification.

At least 10% of the BRCA1/2 tests identify variants of uncertain significance (VUS) while the distinction between pathogenic variants (PV) and benign variants (BV) remains particularly challenging. As a typical tumor suppressor gene, the inactivation of the second wild-type (WT) BRCA1 allele is expected to trigger cancer initiation. Loss of heterozygosity (LOH) of the WT allele is the most frequent mechanism for the BRCA1 biallelic inactivation.

Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences.

Background: Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y ≤ 40 years) and elderly (E ≥ 75 years) patients.

Methods: Open access mutational data (WGS or WES) were collected for TNBC and HGSOC patients.

Survival analysis of young adults from a Brazilian cohort of non-small cell lung cancer patients.

Background: The influence of age at diagnosis in non-small cell lung cancer (NSCLC) prognosis is unclear.

Objectives: To compare in a Brazilian cohort of NSCLC patients of different age groups: 1) The overall survival; 2) Clinical features and treatment options.

Methods: This is a retrospective cohort study using a hospital-based registry, for NSCLC patients registered in years 2000-2009.

Germline and Somatic mutations in postmenopausal breast cancer patients.

Objectives: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations.

Analysis of RPL37A, MTSS1, and HTRA1 expression as potential markers for pathologic complete response and survival.

Background: Non-metastatic locally advanced breast carcinoma (LABC) treatment involves neoadjuvant chemotherapy (NCT). We evaluated the association of clinical-pathological data and immunoexpression of hormone receptors, HER2 and Ki67, and new biomarkers, RPL37A, MTSS1 and HTRA1, with pathological complete response (PCR) or tumour resistance (stable disease or disease progression), disease-free survival (DFS) and cancer-specific survival (CSS).

Methods: This is a retrospective study of 333 patients with LABC who underwent NCT.

Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment.

Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil.

Introduction: The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, ≤ 55 years old) patients.

Methodology: From 2013 to 2015, a total of 88 unrelated and consecutive patients diagnosed with EOGC were enrolled.

Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation.

Objective: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation.

Methods: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed.

Clinical stage and histological type of the most common carcinomas diagnosed in young adults in a reference cancer hospital.

Objectives: Cancer in young adults represents a great challenge, both biologically and socially, and understanding the unique characteristics of neoplasms in this age group is important to improving care. We aimed to evaluate the most common carcinomas and their characteristics, such as histological type and clinical stage, in young adults in the largest cancer hospital in Latin America.

Methods: The hospital registry was consulted for the period between 2008 and 2014.

Survival and prognosis of young adults with gastric cancer.

Objectives: Survival data for young adults (YA) with gastric cancer is conflicting and scarce in Brazil. The aim of this study was to compare the clinicopathological factors and survival rates of younger and older patients with gastric cancer.

Methods: Hospital registries for 294 gastric cancer patients from a reference cancer hospital in São Paulo, Brazil, were consulted for the retrieval of clinicopathological information and follow-up time.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up.

Objective:: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer.

Methods:: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence.

Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil.

Background: Approximately 8-15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer.

The role of oncoplastic breast conserving treatment for locally advanced breast tumors. A matching case-control study.

Background: Breast conserving surgery (BCS) after neoadjuvant chemotherapy (NC) in patients with locally advanced breast cancer (LABC) is an infrequent procedure. In these patients the association with BCS and oncoplastic surgery (OS) is reported as a possible procedure in case-series, but there are limited case-control studies.

Methods: A matched case-control study evaluated LABC submitted to NC and BCS.

Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis.

Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC).

Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed.

Association of family risk and lifestyle/comorbidities in ovarian cancer patients.

Objectives: to analyze factors that might indicate familial predisposition for ovarian cancer in patients diagnosed with this disease.

Methods: in a prospective single center cohort study at the Institute of Cancer of the State of São Paulo (ICESP), 51 women diagnosed with ovarian cancer were included. Familial predisposition for ovarian cancer was defined as having a higher than 10% chance of having a BRCA1/2 mutation according to the Manchester scoring system, a validated method to assess the likelihood of mutation detection.

Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series.

CAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis.

Breast cancer tissue slices as a model for evaluation of response to rapamycin.

Rapamycin is a selective inhibitor of the mammalian target of rapamycin (mTOR), a regulator kinase that integrates growth factors signaling via the phosphoinositide-3-kinase pathway and that has emerged as a novel therapeutic modality in breast cancer (BC). We propose a pre-clinical "ex-vivo" personalized organotypic culture of BC that preserves the microenvironment to evaluate rapamycin-mediated gene expression changes. Freshly excised ductal invasive BC slices, 400 μm thick (n=30), were cultured in the presence or absence (control) of rapamycin (20 nM) for 24 h.

Calcitriol supplementation effects on Ki67 expression and transcriptional profile of breast cancer specimens from post-menopausal patients.

Background & Aims: High concentration of 1,25(OH)2D3 (50-100 nM), which cause hypercalcemia in vivo, induce the hormone transcriptional targets and exert antiproliferative effects in cultured breast cancer lineages, however, no studies investigated whether these effects might be reproduced in tumor specimens in vivo. Our aim was to evaluate the effects of calcitriol supplementation on the proliferative index (Ki67 expression) and gene expression profile of post-menopausal breast cancer samples.

Methods & Results: Tumor samples were collected from 33 patients, most of whom (87.

Transcriptional effects of 1,25 dihydroxyvitamin D(3) physiological and supra-physiological concentrations in breast cancer organotypic culture.

Background: Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)(2)D(3) (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)(2)D(3) in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)(2)D(3) at concentrations that can be attained in vivo.

Methods: Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)(2)D(3) 0.