Prevention of Ovarian Cancer: Where are We Now and Where are We Going?

Purpose Of Review: To describe current and future strategies to reduce the burden of ovarian cancer through prevention.

Recent Findings: Current strategies in genetic testing are missing a substantial number of individuals at risk, representing a missed opportunity for ovarian cancer prevention. Past efforts at screening and early detection have thus far failed to improve ovarian cancer mortality, and novel techniques are needed.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone.

Adoption of Universal Testing in Endometrial Cancers for Microsatellite Instability Using Next-Generation Sequencing.

Purpose: To assess implementation of a next-generation sequencing (NGS) assay to detect microsatellite instability (MSI) as a screen for Lynch syndrome (LS) in endometrial cancer (EC), while determining and comparing characteristics of the four molecular subtypes.

Methods: A retrospective review was performed of 408 total patients with newly diagnosed EC: 140 patients who underwent universal screening with NGS and 268 patients who underwent screening via mismatch repair immunohistochemistry (MMR IHC) as part of a historical screening paradigm. In the NGS cohort, incidental and mutations along with MSI were identified and used to characterize EC into molecular subtypes: -ultramutated, MSI high (MSI-H), -mutated, and no specific molecular profile (NSMP).

Genomic and epigenomic alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas.

Triple-negative breast cancer (TNBC) and ovarian carcinomas (OvCas) with promoter methylation (meth) respond more poorly to alkylating agents compared to those bearing mutations in and (mut). This is a conundrum given the biologically equivalent homologous recombination deficiency (HRD) induced by these genetic and epigenetic perturbations. We dissected this problem through detailed genomic analyses of TNBC and OvCa cohorts and experimentation with patient-derived xenografts and genetically engineered cell lines.

Development and Validation of a Model for Opioid Prescribing Following Gynecological Surgery.

Importance: Overprescription of opioid medications following surgery is well documented. Current prescribing models have been proposed in narrow patient populations, which limits their generalizability.

Objective: To develop and validate a model for predicting outpatient opioid use following a range of gynecological surgical procedures.

Progesterone potentiates the growth inhibitory effects of calcitriol in endometrial cancer via suppression of CYP24A1.

Here, we evaluated the expression of CYP24A1, a protein that inactivates vitamin D in tissues. CYP24A1 expression was increased in advanced-stage endometrial tumors compared to normal tissues. Similarly, endometrial cancer cells expressed higher levels of CYP24A1 than immortalized endometrial epithelial cells.

Progestins inhibit calcitriol-induced CYP24A1 and synergistically inhibit ovarian cancer cell viability: An opportunity for chemoprevention.

Objectives: Previously we have shown in endometrial cells that progesterone (P4) and calcitriol (CAL, 1,25(OH)2D3) synergistically promote apoptosis and that progestins induce expression of the vitamin D receptor. In the current study we examined the progestin/vitamin D combination in ovarian cells and searched for other progestin-related effects on vitamin D metabolism that may underlie the novel interaction between progestins and vitamin D, including whether progestins inhibit CYP24A1, the enzyme that renders CAL inactive.

Methods: We investigated the impact of P4 on CAL-induced CYP24A1 expression in cancer cell lines expressing progesterone receptors (PRs), [OVCAR-5, OVCAR-3-PGR (PR-transfected OVCAR-3 ovarian line), and T47D-WT, T47D-A and T47D-B (breast lines expressing PRs or individual PR isoforms)] or lines that do not express PRs (OVCAR-3 and T47D-Y).

Psychological factors are associated with changes in the health-related quality of life in inflammatory bowel disease.

Background: The effect of different sociodemographic and clinical variables on the health-related quality of life (HRQOL) of patients with inflammatory bowel disease (IBD) is currently known, but the influence of psychological factors has not been sufficiently explored. The objective of this study was to identify psychological predictors of HRQOL in patients with IBD.

Methods: A cross-sectional prospective study was undertaken including 875 consecutive IBD patients.

How do psychological variables influence coping strategies in inflammatory bowel disease?

Background: Adjusting to chronic disease is a complex process and one that, in the case of inflammatory bowel disease (IBD), has received very little attention. The objectives of this study were to identify coping strategies used by patients with IBD and to explore how these strategies are related to psychological characteristics.

Methods: A transversal study was designed in which 875 patients with IBD were prospectively enrolled.