Proliferation of the Fallopian Tube Fimbriae and Cortical Inclusion Cysts: Effects of the Menstrual Cycle and the Levonorgestrel Intrauterine Contraceptive System.

Background: The objectives of this study were (i) to explore whether differences in cell proliferation may help explain why most high-grade serous ovarian cancers (HGSOC) arise in the fallopian tube fimbriae (FTF) rather than in ovarian cortical inclusion cysts (CIC); (ii) to compare premenopausal and postmenopausal FTF proliferation as a reason why the age incidence of HGSOC increases at a slower rate after menopause; and (iii) to compare FTF proliferation in cycling women and women using the levonorgestrel intrauterine contraceptive system (Lng-IUS) to see whether proliferation on the Lng-IUS was lower.

Methods: We studied 60 women undergoing a salpingo-oophorectomy. We used Ki67, paired-box gene 8 (PAX8, Müllerian marker), and calretinin (mesothelial marker) to study FTF and CIC proliferation.

Management of high, moderate, and low penetrance ovarian cancer susceptibility mutations: an assessment of current risk reduction practices.

Objective: Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology.

Methods: Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities.

Risk-Reducing Salpingo-Oophorectomy and Breast Cancer Risk Reduction in the Gynecologic Oncology Group Protocol-0199 (GOG-0199).

Background: Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in or (), a finding that has recently been questioned.

Methods: We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group.

Prospective follow-up of quality of life for participants undergoing risk-reducing salpingo-oophorectomy or ovarian cancer screening in GOG-0199: An NRG Oncology/GOG study.

Background: Risk-reducing salpingo-oophorectomy (RRSO) and ovarian cancer screening (OCS) are management options for women at increased risk of ovarian cancer. Long-term effects of these interventions on quality of life (QOL) are not well understood.

Methods: GOG-0199 is a prospective cohort study of women at increased ovarian cancer risk who chose either RRSO or OCS as their risk management intervention.

The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.

Purpose: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients.

Evolving Intersection Between Inherited Cancer Genetics and Therapeutic Clinical Trials in Prostate Cancer: A White Paper From the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium.

Purpose: Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials.

Methods: The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes.

Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer.

Background: The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer.

Design: We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis.

High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes.

Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking. Two radiologists independently reviewed the CT findings for various qualitative CT features.

Mortality reduction and cost-effectiveness of performing hysterectomy at the time of risk-reducing salpingo-oophorectomy for prophylaxis against serous/serous-like uterine cancers in BRCA1 mutation carriers.

Objective: To estimate the survival benefit and cost-effectiveness of performing hysterectomy during risk-reducing salpingo-oophorectomy (RRSO) for BRCA1 mutation carriers.

Methods: Based on a recent prospective cohort study indicating an elevated incidence of serous/serous-like uterine cancers among BRCA1 mutation carriers, we constructed a modified Markov decision model from a payer perspective to inform decisions about performance of hysterectomy during RRSO at age 40. We assumed patients had previously undergone a risk-reducing mastectomy and had a residual risk of death from breast or ovarian cancer.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations.

Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations.

Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.

Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.

Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes.

Characteristic histopathologic features have been described in high-grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation.

Development and validation of a clinical score for predicting risk of adenoma at screening colonoscopy.

Background: Currently, no clinical tools use demographic and risk factor information to predict the risk of finding an adenoma in individuals undergoing colon cancer screening. Such a tool would be valuable for identifying those who would most benefit from screening colonoscopy.

Methods: We used baseline data from men and women who underwent screening colonoscopy from the randomized, multicenter National Colonoscopy Study (NCS) to develop and validate an adenoma risk model.

Pathologic findings at risk-reducing salpingo-oophorectomy: primary results from Gynecologic Oncology Group Trial GOG-0199.

Purpose: Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study.

Assessment of individuals with BRCA1 and BRCA2 large rearrangements in high-risk breast and ovarian cancer families.

BRCA1/2 large rearrangement (LR) testing has been available to patients since 2006. Three existing models commonly used in cancer genetics clinical and research settings (BRCAPRO, Penn II and Myriad II) have not been assessed for their performance in predicting the presence of BRCA1/2 large genomic rearrangements in patients who do not have mutations detectable by the traditional Sanger sequencing approach. This study sought to determine if there is an optimal pre-test probability "cut off" value, calculated using these models, to optimize detection of large rearrangements (LRs).

Invasion patterns of metastatic high-grade serous carcinoma of ovary or fallopian tube associated with BRCA deficiency.

High-grade serous carcinomas of the uterine adnexa with BRCA1 deficiency (high-grade serous carcinomas-BRCA) have recently been described to demonstrate characteristic histopathological features. We hypothesize that metastatic high-grade serous carcinomas-BRCA cases exhibit characteristic morphological features as well. We studied 102 high-grade serous carcinomas with known BRCA1 and BRCA2 genotype from the archives of the Department of Pathology at Memorial Sloan-Kettering Cancer Center.

Clinical outcome of isolated serous tubal intraepithelial carcinomas (STIC).

Objective: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women with BRCA mutation due to increased risk of pelvic serous carcinoma. Serous tubal intraepithelial carcinoma (STIC) is a pathologic finding of unknown clinical significance. This study evaluates the clinical outcome of patients with isolated STIC.

Outcomes of primary surgical cytoreduction in patients with BRCA-associated high-grade serous ovarian carcinoma.

Objective: BRCA-associated and sporadic ovarian cancers have different pathologic and clinical features. Our goal was to determine if BRCA mutation status is an independent predictor of residual tumor volume following primary surgical cytoreduction.

Methods: We conducted a retrospective analysis of patients with FIGO stage IIIC-IV high-grade serous ovarian cancer classified for the presence or absence of germline BRCA mutations.

Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma.

This study was undertaken with the hypothesis that certain common morphologic features of ovarian carcinomas are predictably associated with BRCA1 and BRCA2 deficiencies. We selected 43 high-grade serous carcinomas diagnosed at Memorial Sloan-Kettering Cancer Center that were studied as part of The Cancer Genome Atlas pilot project. In addition to 12 randomly selected nonfamilial BRCA-unassociated cases, all 31 Memorial Sloan-Kettering Cancer Center cases with BRCA1 or BRCA2 abnormality were included (n=43).