Objective
Solid tumors often establish a procoagulable state that can lead to venous thromboembolism (VTE). Although some of the key genes involved in this process are known, no previous study has ...compared the “coagulome”, i.e., the expression of coagulation/fibrinolysis genes, across different primary tumor types. It is also unclear whether the coagulome is associated with specific characteristics of the tumor microenvironment (TME). We aimed to address this question.
Methods
We analyzed the expression of the genes
F3, PLAU, PLAT, PLAUR, SERPINB2,
and
SERPINE1
in 32 cancer types using data from The Cancer Genome Atlas (TCGA) and other freely available resources.
Results
We identified specific expression patterns of procoagulant and fibrinolytic genes. The expression of the Tissue Factor (
F3
) was found to be tumor type dependent, with the highest expression in glioblastoma (GBM), a highly procoagulable tumor type. Conversely, high expression of the fibrinolysis gene cluster
PLAU, PLAUR, SERPINE1
was consistently linked to the characteristics of the TME (monocytic infiltration) and high expression of important checkpoints of the immune response, such as PD-L2 and CD276/B7-H3.
Conclusion
These tumor-specific patterns of expression might partially explain the differences in VTE risk among tumor types. We propose that biomarkers of coagulation fibrinolysis might provide valuable information about the TME in cancer patients.
For trying to help physicians in counseling their young patients with breast cancer interested in fertility preservation and future reproductive plans, this manuscript aims to perform an overview of ...the main available data on 10 controversies in this field.
Thanks to the improvement in patients' prognosis, a growing attention towards fertility and pregnancy issues has been given over the past years and is currently provided to young breast cancer patients. However, several grey zones persist in many domains of this field and some physicians are still uncomfortable to deal with these issues.
Despite the great number of breast cancer patients experiencing fertility and pregnancy concerns at the time of diagnosis, the pursuit of fertility preserving strategies is realized only for a small proportion of them. The lack of adequate oncofertility counseling at the time of anticancer treatment decisions and the high costs of fertility preserving procedures can be considered the main explanations for these findings. The several ongoing registries and prospective studies investigating fertility and pregnancy issues in young breast cancer patients are crucial to acquire more robust data and try to address and solve the still unmet controversies in this field.
Background
Oral squamous cell carcinoma (OSCC) is the most frequent type of tumor arising from the oral cavity. Surgery is the cornerstone of the treatment of these cancers. Tumor biology has long ...been overlooked as an important contributor to the outcome of surgical procedures, but recent studies are challenging this concept. Molecular analyses of tumor DNA or RNA provide a rich source of information about the biology of OSCC.
Methods
We searched for relevant articles using PubMed. We examined in particular the prospect of applying molecular methods for minimally invasive exploration of OSCC biology.
Results
We examined five potential applications of genomics to the surgical management and study of OSCC: i) assessing oral potentially malignant lesions; ii) tumor staging prior to surgery; iii) predicting postoperative risk in locally advanced tumors; iv) measuring minimal residual disease and optimizing the longitudinal monitoring of OSCC; and v) predicting the efficacy of medical treatment.
Conclusions
Genomic information can be harnessed in order to identify new biomarkers that could improve the staging, choice of therapy and management of OSCC. The identification of new biomarkers is awaited for better personalization of the surgical treatment of OSCC.
Perineural invasion (PNI) is a pathological feature frequently observed in head and neck squamous cell carcinoma (HNSCC). The difficulties of pathological standardization and the lack of a simple ...validated experimental model to study PNI render its analysis complex. Here, we aim to summarize the recent advances in the understanding of the biology of PNI in HNSCC and their potential clinical implications.
PNI is a multistep process leading to a dialogue between cancer cells and nerve fibers in HNSCC. Recent studies have identified some of the active molecular mechanisms involved in PNI. Comprehensive studies addressing the transcriptional regulation of PNI bring interesting perspectives for a standardized molecular diagnosis of PNI and a better assessment of its contribution to the aggressiveness of HNSCC.
Perineural invasion is a complex process that reflects specific tumor biology. In addition to unveiling new fundamental concepts about the tumor microenvironment, research on PNI promises to identify new biomarkers, enabling progress in therapeutic development against HNSCC.
Young women with germline
mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients ...with
mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline
mutations.
This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline
mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors.
Of 1,252 patients with germline
mutations (
, 811 patients;
, 430 patients;
, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio HR, 0.87; 95% CI, 0.61 to 1.23;
= .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56;
= .66) were observed between the pregnancy and nonpregnancy cohorts.
Pregnancy after breast cancer in patients with germline
mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with
-mutated breast cancer interested in future fertility.
Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic PIK3CA mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, ...such as alpelisib. The aim of this study was to evaluate the detection rate of circulating PIK3CA mutation in locally-advanced IBC (LAIBC) patients harbouring a PIK3CA mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel. PIK3CA mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a PIK3CA mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating PIK3CA mutations were found in 6/11 (55%). Among the 41 patients without PIK3CA mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating PIK3CA mutation was identified. Our results revealed no prognostic or predictive value of PIK3CA mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating PIK3CA mutation was identified in 55% of LAIBC patients with PIK3CA-mutated tumours, while no circulating mutation was found among patients with PI3KCA wild-type tumours.
Purpose
Accurate diagnosis and prediction of loss of ovarian function after chemotherapy for premenopausal women with early breast cancer (eBC) is important for future fertility and clinical ...decisions regarding the need for subsequent adjuvant ovarian suppression. We have investigated the value of anti-mullerian hormone (AMH) as serum biomarker for this.
Methods
AMH was measured in serial blood samples from 206 premenopausal women aged 40–45 years with eBC, before and at intervals after chemotherapy. The diagnostic accuracy of AMH for loss of ovarian function at 30 months after chemotherapy and the predictive value for that of AMH measurement at 6 months were analysed.
Results
Undetectable AMH showed a high diagnostic accuracy for absent ovarian function at 30 months with AUROC 0.89 (96% CI 0.84–0.94,
P
< 0.0001). PPV of undetectable AMH at 6 months for a menopausal estradiol level at 30 months was 0.77. In multivariate analysis age, pre-treatment AMH and FSH, and taxane treatment were significant predictors, and combined with AMH at 6 months, gave AUROC of 0.90 (95% CI 0.86–0.94), with PPV 0.79 for loss of ovarian function at 30 months. Validation by random forest models with 30% data retained gave similar results.
Conclusions
AMH is a reliable diagnostic test for lack of ovarian function after chemotherapy in women aged 40–45 with eBC. Early analysis of AMH after chemotherapy allows identification of women who will not recover ovarian function with good accuracy. These analyses will help inform treatment decisions regarding adjuvant endocrine therapy in women who were premenopausal before starting chemotherapy.
Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance ...of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth. The aim of this systematic review is to provide an overview of the available data concerning
alterations and glioblastoma in terms of incidence, physiopathological understanding, and potential therapeutic implications.
PDF
