Real-world outcomes of neoadjuvant chemotherapy for advanced ovarian cancer: What happens to patients who never undergo surgery?

Objectives: To describe the outcomes of patients with advanced ovarian cancer (OC) treated with neoadjuvant chemotherapy who do and do not undergo interval cytoreductive surgery (ICS).

Methods: This was a retrospective cohort study of patients with stage III/IV epithelial OC who began treatment with at least three cycles of chemotherapy from 2017 to 2022. Primary analysis compared 3-year progression-free (PFS) and overall (OS) survival for patients who underwent ICS to those who received chemotherapy only (planned ICS not performed).

Genomic and Immune Landscape of Pancreatic Ductal Adenocarcinoma Associated with Germline Pathogenic Variants in ATM.

Background: Germline pathogenic variants (PVs) in ATM increase the risk of pancreatic ductal adenocarcinoma (PDAC) but the underlying tumor biology of PDAC associated with germline PVs in ATM have not been adequately explored.

Experimental Design: Whole-genome (WGS), whole-exome (WES), and RNA-sequencing were performed on PDAC tumors from 25 germline ATM PVs carriers diagnosed at Mayo Clinic between 2007 and 2017. Somatic and copy number alterations, mutational signatures, transcriptomic subtypes, and the immune landscape were evaluated.

Real-World Germline BRCA Testing, Poly(ADP-ribose) Polymerase Inhibitor Utilization, and Survival Outcomes in Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.

Purpose: Testing for germline and/or mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline and/or (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited.

Methods: Deidentified patient data from adults diagnosed with HER2- mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database.

Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification.

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS.

Breast Cancer Risk Modification in Women with Pathogenic Variants in BRCA1, BRCA2, ATM, CHEK2, and PALB2.

There is limited information on whether established risk factors increase breast cancer risk from PVs. In the WHI, PV carriers had no substantial (≥2-fold) increase with most risk factors, except potentially MHT in ATM or CHEK2 carriers. The results may inform counseling and research on MHT.

ECPPF stratification identifies occult high-risk subgroups in stage I, grade 1 or 2, ≤50 % invasive endometrial cancer: Candidates for adjuvant therapy.

Objective: To determine whether stratification with ECPPF (E2F1 + CCNA2 log2 expression and POLE, PPP2R1A, and FBXW7 variants) could identify occult cases of high-risk endometrial cancer (EC) in a traditionally low-risk cohort.

Methods: We identified 97 cases of clinicopathologic low-risk endometrioid EC (defined as stage I, grade 1 or 2, limited [≤50 %] myometrial invasion) from The Cancer Genome Atlas (TCGA). Twelve cases had POLE mutations (mu) and 15 had PPP2R1Amu or FBXW7mu.

Interactions Between Genetic and Epidemiological Factors Influencing Mammographic Density.

Studies have identified genetic and epidemiological factors associated with mammographic density (MD) phenotypes. However, MD-associated genetic variants only account for a small proportion of the total estimated heritability. Interrogating interactions between genetic and epidemiological factors could potentially identify additional MD-associated loci, expand our understanding of the genetic basis of MD phenotypes, and clarify how epidemiological factors modulate relationships between genetic variants and MD.

Germline-Somatic Interactions in BRCA-Associated Cancers: Unique Molecular Profiles and Clinical Outcomes Linking ATM to TP53 Synthetic Essentiality.

Purpose: Germline alterations in homologous recombination repair (gHRR) genes affect the pathogenesis, treatment options, and survival of patients with cancer. However, distinct gHRR gene alterations may differentially affect treatment response and oncogenic signaling. In this study, we interrogated genomic and transcriptomic data and assessed clinical outcomes of patients with gHRR mutations across four BRCA-associated cancers (breast, ovarian, pancreatic, and prostate cancers) to identify therapeutic vulnerabilities.

Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Real-World Evidence on Prescribing Patterns and Clinical Outcomes of Metastatic Breast Cancer Patients Treated with PARP Inhibitors: The Mayo Clinic Experience.

Purpose: This study evaluates real-world outcomes, toxicities, and prescribing patterns of PARP inhibitors (PARPis) for the treatment of metastatic breast cancer (MBC).

Patients And Methods: Electronic health records of 62 MBC patients treated with olaparib (n = 48) or talazoparib (n = 14) at Mayo Clinic System between 2017 and 2022 were analyzed. Time-to-treatment-failure (TTF) was assessed utilizing the Kaplan-Meier method.

Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.

Purpose: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

Experimental Design: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.

A deep dive into neonatal well-being and anesthesia in cesarean sections: From procedure to outcome.

This observational study analyzed data from 502 participants undergoing cesarean section (CS) procedures at an obstetrics and gynecology department, aiming to explore anesthesia practices, neonatal outcomes, and demographic characteristics within the cohort. Participants, aged 17 to 59 years with a mean age of 32.23 years, were enrolled based on the clinical necessity for cesarean delivery during the study period.

Physical and psychological distress amongst patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer.

Objective: This study compares baseline clinical characteristics, physical function testing, and patient-reported outcomes for patients undergoing primary cytoreductive surgery versus neoadjuvant chemotherapy, with the goal of better understanding unique patient needs at diagnosis.

Methods: Patients with suspected advanced stage (IIIC/IV) epithelial ovarian cancer undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy were enrolled in a single-institution, non-randomized prospective behavioral intervention trial of prehabilitation. Baseline clinical characteristics were abstracted.

Anastrozole Dose Escalation for Optimal Estrogen Suppression in Postmenopausal Early-Stage Breast Cancer: A Prospective Trial.

Purpose: We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event.

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Discordance in Recommendation Between Next-Generation Sequencing Test Reports and Molecular Tumor Boards in India.

Purpose: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports.

Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain.

Variants of uncertain significance (VUSs) in BRCA2 are a common result of hereditary cancer genetic testing. While more than 4,000 unique VUSs, comprised of missense or intronic variants, have been identified in BRCA2, the few missense variants now classified clinically as pathogenic or likely pathogenic are predominantly located in the region encoding the C-terminal DNA binding domain (DBD). We report on functional evaluation of the influence of 462 BRCA2 missense variants affecting the DBD on DNA repair activity of BRCA2 using a homology-directed DNA double-strand break repair assay.

Non-Communicable Diseases among Women of Reproductive Age Visiting the Department of Obstetrics and Gynecology of a Tertiary Care Hospital.

Introduction: Non-communicable diseases are a significant cause of mortality worldwide, posing a substantial risk to women's health, as stated by the World Health Organization. In Nepal, a survey revealed that 10.5% of the population suffers from hypertension.

Induction of Labour among Pregnant Women in the Department of Obstetrics and Gynaecology in a Tertiary Care Centre.

Introduction: Induction of labour is the artificial initiation of uterine contraction by various means such as medical, surgical or mechanical with the aim of achieving vaginal delivery. Misoprostol, a prostaglandin E1 analogue is used popularly for the induction of labour in resource-limited health centres. The aim of the study was to find out the prevalence of induction of labour among pregnant women in the Department of Obstetrics and Gynaecology in a tertiary care centre.

Obstetric Cholestasis among Pregnant Women Visiting a Tertiary Care Centre.

Introduction: Obstetric cholestasis is one of the most frequent hepatic disorders specific to pregnancy. It occurs commonly during the latter half of pregnancy. The data regarding this issue is rare in our settings.