Genetic risk assessment in breast and gynecologic malignancies- what's to know in 2024?

PURPOSE OF REVIEW: Hereditary cancer risk assessment and counseling have become integral in oncology care, especially in breast and gynecologic malignancies where genetic test results impact management. However, a large number of patients who could benefit from genetic testing are not getting tested. As such, genetic risk assessment and counseling methods have had to evolve to meet the needs of this expanding patient population. RECENT FINDINGS: "Mainstreaming" genetic testing is an initiative to incorporate genetic testing into routine cancer care in lieu of the traditional genetic counseling model to improve uptake of testing while minimizing expansion of genetic counselor and clinic resources. These models have performed well in various institutions demonstrating an improvement in clinical efficacy. However, missed opportunities from the preventive care standpoint, a core value of cancer genetics risk assessment, have become apparent. The focus of these models is on the patient's cancer diagnosis and comprehensive/familial genetic risk assessment is not often completed. SUMMARY: Identifying patients at an increased risk of cancer, even in the absence of a hereditary cancer predisposition syndrome, is important in tailoring screening and preventive measures. As we look to the future, we need to critically approach mainstreaming and determine how to reincorporate comprehensive genetic risk assessment into our models.

Tackling Gynecologic Cancer Disparities: An Assessment of 2 Interventions for Improving Information Exchange With Racial/Ethnic Communities.

Racial health disparities continue to greatly impact the incidence and mortality rates of gynecologic cancers. Although there are many drivers for these disparities, limited inclusion of vulnerable populations in clinical research and narrowed medical knowledge of patients are large contributors that disproportionately affect racial/ethnic communities. To mitigate these disparities, we must look for avenues that connect patients from these communities to cancer researchers. In this review, we summarize 2 projects that can serve as models for future interventions that promote education and engagement in clinical research for populations most impacted by gynecologic cancer disparities.

Cost-effectiveness Analysis of Genotype-Specific Surveillance and Preventive Strategies for Gynecologic Cancers Among Women With Lynch Syndrome.

Importance: With the expansion of multigene testing for cancer susceptibility, Lynch syndrome (LS) has become more readily identified among women. The condition is caused by germline pathogenic variants in DNA mismatch repair genes (ie, MLH1, MSH2, MSH6, and PMS2) and is associated with high but variable risks of endometrial and ovarian cancers based on genotype. However, current guidelines on preventive strategies are not specific to genotypes. Objective: To assess the cost-effectiveness of genotype-specific surveillance and preventive strategies for LS-associated gynecologic cancers, including a novel, risk-reducing surgical approach associated with decreased early surgically induced menopause. Design, Setting, and Participants: This economic evaluation developed a cohort-level Markov simulation model of the natural history of LS-associated gynecologic cancer for each gene, among women from ages 25 to 75 years or until death from a health care perspective. Age was varied at hysterectomy and bilateral salpingo-oophorectomy (hyst-BSO) and at surveillance initiation, and a 2-stage surgical approach (ie, hysterectomy and salpingectomy at age 40 years and delayed oophorectomy at age 50 years [hyst-BS]) was included. Extensive 1-way and probabilistic sensitivity analyses were performed. Interventions: Hyst-BSO at ages 35 years, 40 years, or 50 years with or without annual surveillance beginning at age 30 years or 35 years or hyst-BS at age 40 years with oophorectomy delayed until age 50 years. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) between management strategies within an efficiency frontier. Results: For women with MLH1 and MSH6 variants, the optimal strategy was the 2-stage approach, with respective ICERs of $33 269 and $20 008 compared with hyst-BSO at age 40 years. Despite being cost-effective, the 2-stage approach was associated with increased cancer incidence and mortality compared with hyst-BSO at age 40 years for individuals with MLH1 variants (incidence: 7.76% vs 3.84%; mortality: 5.74% vs 2.55%) and those with MSH6 variants (incidence: 7.24% vs 4.52%; mortality: 5.22% vs 2.97%). Hyst-BSO at age 40 years was optimal for individuals with MSH2 variants, with an ICER of $5180 compared with hyst-BSO at age 35 years, and was associated with 4.42% cancer incidence and 2.97% cancer mortality. For individuals with PMS2 variants, hyst-BSO at age 50 years was optimal and all other strategies were dominated; hyst-BSO at age 50 years was associated with an estimated cancer incidence of 0.68% and cancer mortality of 0.29%. Conclusions and Relevance: These findings suggest that gene-specific preventive strategies for gynecologic cancers in LS may be warranted and support hyst-BSO at age 40 years for individuals with MSH2 variants. For individuals with MLH1 and MSH6 variants, these findings suggest that a novel 2-stage surgical approach with delayed oophorectomy may be an alternative to hyst-BSO at age 40 years to avoid early menopause, and for individuals with PMS2 variants, the findings suggest that hyst-BSO may be delayed until age 50 years.

Using Inside Knowledge Campaign Materials to Improve Gynecologic Cancer Knowledge in Underserved Women.

Purpose: About 30,000 U.S. women die each year from gynecologic cancer, which disproportionately affects underserved and minority populations. This project aimed at increasing and assessing awareness of risk, symptoms, and recommended screenings and prevention activities in underserved women, through unique collaboration between the Centers for Disease Control and Prevention's (CDC) Inside Knowledge (IK) campaign, which was designed to educate women about gynecologic cancer, and the CDC's national network of organizations to reduce cancer-related disparities. Materials and Methods: CDC's national network and the IK campaign partnered to deliver tailored educational sessions about gynecologic cancer to three populations of women served by the participant organizations. Participant organizations included the National Behavioral Health Network (NBHN), Nuestras Voces (NV), and SelfMade. Pre- and post-session questionnaires were administered to assess knowledge changes. Results: Knowledge changes for risk factors, screening, and HPV vaccination varied by network organization, but all sessions increased correct identification of some symptoms. Baseline knowledge also varied among organization participants. Conclusions: Sessions were effective in increasing awareness of gynecologic cancer among underserved women; however, organizational information uptake differed. Additional resources containing specific interventions appropriate to particular underserved populations may be beneficial in increasing healthy behaviors, leading to a reduction in gynecologic cancer disparities.

A Systematic Assessment of Google Search Queries and Readability of Online Gynecologic Oncology Patient Education Materials.

The Internet is a major source of health information for gynecologic cancer patients. In this study, we systematically explore common Google search terms related to gynecologic cancer and calculate readability of top resulting websites. We used Google AdWords Keyword Planner to generate a list of commonly searched keywords related to gynecologic oncology, which were sorted into five groups (cervical cancer, ovarian cancer, uterine cancer, vulvar cancer, vaginal cancer) using five patient education websites from sgo.org . Each keyword was Google searched to create a list of top websites. The Python programming language (version 3.5.1) was used to describe frequencies of keywords, top-level domains (TLDs), domains, and readability of top websites using four validated formulae. Of the estimated 1,846,950 monthly searches resulting in 62,227 websites, the most common was cancer.org . The most common TLD was *.com. Most websites were above the eighth-grade reading level recommended by the American Medical Association (AMA) and the National Institute of Health (NIH). The SMOG Index was the most reliable formula. The mean grade level readability for all sites using SMOG was 9.4 ± 2.3, with 23.9% of sites falling at or below the eighth-grade reading level. The first ten results for each Google keyword were easiest to read with results beyond the first page of Google being consistently more difficult. Keywords related to gynecologic malignancies are Google-searched frequently. Most websites are difficult to read without a high school education. This knowledge may help gynecologic oncology providers adequately meet the needs of their patients.

Disease burden of human papillomavirus infection in the Netherlands, 1989-2014: the gap between females and males is diminishing.

PURPOSE: Besides cervical cancer, HPV infection is linked to a multitude of diseases in both males and females, suggesting that vaccination programmes should be re-evaluated, with a judicious assessment made of the disease burden stratified by sex, age, and genotype. Projections of burden into the near future are also needed to provide a benchmark for evaluating the impact of vaccination programmes, and to assess the need for scaling-up preventive measures. METHODS: Using the disability-adjusted life-years (DALY) measure, we estimated the total HPV-associated disease burden in the Netherlands. Annual cancer registrations over the period 1989-2014 for all cancers with an aetiological link to HPV infection were retrieved, supplemented by incidence data on high-grade cervical intraepithelial neoplasia (CIN) and anogenital warts. RESULTS: Over the recent period 2011-2014, the average annual HPV disease burden was 10,600 DALYs (95% credible interval (CrI):10,260-10,960) in females and 3,346 DALYs (95% CrI: 2,973-3,762) in males. Burden was dominated by cervical cancer, but its share amongst women decreased from 89% in 1989 to 77% in 2014. The male share of the total disease burden increased from 9.8% in 1989 to 26% in 2014. In 2023 (before the expected clinical impact from vaccinating girls), total burden is forecasted at 1.3-fold larger than in 2014. CONCLUSIONS: The HPV-associated disease burden is higher than that reported for any other infectious disease in the Netherlands, with a larger burden observed in women than in men. The rapidly rising male share of the total burden underlines the prioritization of male HPV-related disease in prevention programmes.

Knowledge and attitudes of women regarding gynaecological cancer prevention in an urban area of Greece in financial crisis.

INTRODUCTION: Preventive gynaecological examinations (PGEs) are the main means of monitoring gynaecological cancers across the developed world. The purpose of this study was to investigate the perceptions and attitudes of women of a regional municipality of Greece, regarding preventive gynaecological examinations amid economic crisis. MATERIAL AND METHODS: The study included 360 women aged 20-70 years, who lived in an urban area of Greece. A specialised, valid and anonymous questionnaire that included questions about perceptions and attitudes regarding preventive gynaecological examinations was used. The data analysis was performed using the statistical package spss 21. RESULTS: It was found that women who lived in less developed areas had had lower educational levels and higher abstinence rates from medical examinations. The main source of information about sexually transmitted diseases was their social circle (48%), but the gynaecologist is the one preferred (54.8) to inform about preventive gynaecological examinations. Thirty per cent of the participants had never have a mammogram, while 33.9% of the sample did not show the same result, although considered the Pap test necessary. The main cause of women's abstention of preventive gynaecological examinations is the financial crisis. CONCLUSIONS: The current financial crisis has negatively affected the women's ability to afford gynaecological examinations. Therefore, it is necessary to inform the population about the necessity of preventive gynaecological examinations starting from school age and at the same time, health information and promotion campaigns should be launched at a national level.

[Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model]. / Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión.

OBJECTIVE: To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. MATERIALS AND METHODS: A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. RESULTS: Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. CONCLUSIONS: Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Costo-efectividad de la vacuna tetravalente contra VPH en Argentina, a partir de un modelo dinámico de transmisión / Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model

Objetivo. Evaluar la costo-efectividad (CE) de la vacuna tetravalente contra el virus de papiloma humano (VPH) en Argentina, desde la perspectiva del sistema de salud. Material y métodos. Se utilizó un modelo dinámico de transmisión para estimar el impacto en la incidencia de cáncer de cuello uterino (Cacu), verrugas y otras lesiones, en los años de vida ajustados por calidad (AVAC) y en costos sanitarios. Resultados. La vacuna podría reducir en 60% el riesgo de muerte por Cacu y en 67% el de padecer verrugas genitales. Comparada con no vacunar, la estrategia de vacunación mostró un beneficio incremental promedio de 0.00234 AVAC por persona a un costo incremental de 2.36 dólares, con una CE de 1007.55 dólares por AVAC ganado. Los resultados demostraron ser robustos en el análisis de sensibilidad. Conclusiones. La inmunización resultaría costo-efectiva, con una CE inferior a un producto interno bruto per cápita (15 009 dólares) por AVAC ganado.

Objective. To assess the cost-effectiveness of the quadrivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. Materials and methods. A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. Results. Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. Conclusions. Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained.

Follow-up in Gynecological Malignancies: A State of Art.

OBJECTIVE: The main purpose of this article is to explore the current practice for follow-up of gynecological cancer, pointing out the different procedures, to determine the most clinically and cost-effective surveillance strategies after the primary treatment. MATERIALS AND METHODS: We analyzed the follow up strategies for ovarian, endometrial, and cervical cancer. All of the topics discussed below arose from the "ESGO State of Art Conference-Follow-up in gynaecological malignancies" in Turin, (September 11-13, 2014; http://torino2014.esgo.org/). RESULTS: Physical but these practices should be integrated with biomarkers or imaging strategies. Currently, most recommendations about follow-up are based on retrospective studies and expert opinion, and there is some disagreement on surveillance strategies due to lack of evidence-based knowledge. CONCLUSIONS: All surveillance procedures should be evidence-based with a clearly defined purpose: there is a need for prospective studies to compare the effectiveness of different follow-up regimens measuring overall survival, detection of recurrence, quality of life (QoL), and costs as outcomes.

Economic Considerations on the Follow-Up Practice in Gynecologic Cancers: Few Lights and Many Shadows From a Literature Review.

OBJECTIVE: The aim of this review was to analyze the existing literature on the cost of follow-up in gynecology oncology. METHODS/MATERIALS: We performed a literature search in Medline and NHS CRD (University of Oxford) databases. Research strings were mainly based on MESH terms referring to economic studies and to neoplasms follow-up/aftercare and cancer recurrences. Two independent searches were performed for ovarian neoplasm and uterine neoplasm. Some studies were also identified among the references of the selected articles. Potentially relevant studies were identified based on the title and abstract by 2 independent readers. RESULTS: Finally, the reviewing process selected 2 studies on gynecologic cancers in general, including uterine and ovarian cancers, 3 specific on ovarian cancer, 7 on endometrium, and 9 on cervix. The identified economic literature on economic evaluation of gynecologic cancer follow-up procedures showed to be based on weak evidence of effectiveness and to lack formal methodological approaches. In general, such literature is quite recent, relies on small sample observational studies, and suffers from a lack of financial support. CONCLUSIONS: There are few available lights in economic considerations on gynecologic cancer follow-up, represented by all the published studies, and many shadows that require to be clarified by properly designed randomized trials including cost-effectiveness analysis.

Next-generation sequencing for hereditary breast and gynecologic cancer risk assessment.

PURPOSE OF REVIEW: To summarize advances in next-generation sequencing and their application to breast and gynecologic cancer risk assessment. RECENT FINDINGS: Next-generation sequencing panels of 6-112 cancer-associated genes are increasingly used in patient care. Studies report a 4-16% prevalence of mutations other than BRCA1/2 among patients who meet evidence-based practice guidelines for BRCA1/2 testing, with a high rate (15-88%) of uninterpretable variants of uncertain significance. Despite uncertainty about results interpretation and communication, there is early evidence of a benefit from multiple-gene sequencing panels for appropriately selected patients. SUMMARY: Multiple-gene sequencing panels appear highly promising for the assessment of breast and gynecologic cancer risk, and they may usefully be administered in the context of cancer genetics expertise and/or clinical research protocols.

Outcomes and Cost Analysis in High-Risk Patients Undergoing Simultaneous Free Flap Breast Reconstruction and Gynecologic Procedures.

BACKGROUND: For patients with BRCA mutations, a simultaneous procedure that combines risk-reducing operation of the ovaries with mastectomy and breast reconstruction is an attractive option. The purpose of this study was to assess the outcomes and associated cost of performing simultaneous mastectomy, free flap breast reconstruction (FFR), and gynecologic procedure. METHODS: A retrospective chart review was performed on patients who underwent bilateral FFR from 2005 to 2012. Four hundred twenty-two patients were identified who underwent bilateral breast reconstruction without a simultaneous gynecologic procedure. Forty-two patients were identified who underwent simultaneous FFR and gynecologic procedure. Clinical outcomes, medical and surgical complications, and hospital costs were analyzed and compared between the 2 groups. RESULTS: A total of 928 free flaps were performed on 464 patients. Forty-two patients had a simultaneous gynecologic procedure at the time of breast reconstruction. Twenty-three (54.8%) patients within the study group underwent simultaneous bilateral salpingo oophorectomy (BSO), whereas the other 19 (45.2%) underwent both total abdominal hysterectomy and BSO. Eighty-four free flaps were performed in this cohort (n = 48 muscle-sparing transverse rectus abdominis myocutaneous, n = 28 deep inferior epigastric perforator, n = 4 superficial inferior epigastric perforator, n = 4 transverse upper gracilis). Mean operative time was 573 minutes. Mean hospitalization was 5.3 days. Postoperatively, 4 patients experienced an anastomotic thrombosis; 2 patients had an arterial thrombosis and 2 patients had a venous thrombosis. There were 2 flap failures, 2 patients with mastectomy skin flap necrosis, 11 patients who developed breast wound healing complications, and 6 patients who developed abdominal wound healing complications. Surgical and medical complication rates did not differ significantly between those who had simultaneous procedures, and those who did not. There was a statistically significant difference in the average total cost when comparing the group of patients receiving prophylactic mastectomy/FFR/total abdominal hysterectomy and/or BSO versus the patients who did not have combined gynecologic procedures at the time of reconstruction ($22,994.52 vs $21,029.23, P = 0.0004). CONCLUSIONS: For the high-risk breast cancer patient, a combined mastectomy, free flap reconstruction, and gynecologic procedure represents an attractive and safe option.

Risk-benefit assessment of the combined oral contraceptive pill in women with a family history of female cancer.

INTRODUCTION: Oral contraceptive pills (OCPs) are the most frequently used form of effective, reversible contraception among women of childbearing potential. In the average risk population, OCPs may offer a protective benefit against ovarian, endometrial and colorectal malignancies. In women at high risk for breast, ovarian, endometrial or colorectal malignancies, the risk-benefit profile is less well studied. AREAS COVERED: In this article, we review pertinent literature on the use of OCPs in patients with genetic susceptibilities due to mutations in BRCA1, BRCA2 or mismatch repair genes implicated in hereditary nonpolyposis colorectal cancer as well as those with a strong family history of malignancies associated with these syndromes. EXPERT OPINION: For women at high risk for ovarian, endometrial and/or colorectal malignancies due to genetic susceptibilities or a strong family history, the possibility of chemoprevention with OCPs may be an attractive option; however, the potential increase in breast cancer, although small, must be considered in clinical decision-making. The ultimate decision to use OCPs in a high-risk woman should be based on a consideration of her specific genetic risk, her age, her reproductive plans and her willingness to consider surgical prophylaxis options.

The burden of HPV-associated anogenital cancers.

The epidemiology of anogenital cancers is under going substantial change. Cervical cancer remains a major public health concern, particular in resource-limited settings. Cancers of the anus, penis, vagina and vulva are relatively uncommon cancers, but may be increasing in incidence. The change in occurrence of anogenital cancers may be due to increasing HPV transmission secondary to changes in sexual behaviour. Screening programmes and the HPV vaccine offer optimism that anogenital cancers can be prevented. This article reviews the epidemiology of anogenital cancers with a focus on Scottish data.

Gynecologic cancer prevention and control in the National Comprehensive Cancer Control Program: progress, current activities, and future directions.

Gynecologic cancer confers a large burden among women in the United States. Several evidence-based interventions are available to reduce the incidence, morbidity, and mortality from these cancers. The National Comprehensive Cancer Control Program (NCCCP) is uniquely positioned to implement these interventions in the US population. This review discusses progress and future directions for the NCCCP in preventing and controlling gynecologic cancer.

The burden and costs of prevention and management of genital disease caused by HPV in women: a population-based registry study in Finland.

The aim of this study was to evaluate the total burden and health care provider costs of prevention, management and treatment of HP-related genital disease outcomes including all organized and opportunistic screening tests. Information about HPV-related disease outcomes in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. We estimated the incidence, health care resource use, health provider costs and life years lost due to cervical, vaginal and vulvar cancer and intraepithelial neoplasia (CIN, VaIN, VIN), cervical adenocarcinoma in situ, and external genital warts. The average annual disease burden of HPV-related genital disease in the female population of Finland comprises altogether 241 cases of cervical, vaginal and vulvar cancer, 2,898 new cases of CIN, 34,432 cases of minor cytological abnormalities, and almost 4,000 cases of external genital warts. The total annual costs of screening, further diagnostics and treatment of HPV-related genital disease were € 44.7 million of which the annual costs due to cervical cancer screening were € 22.4 million and due to diagnostics, management and treatment of HPV-related genital disease outcomes were € 22.3 million. The latter included € 8.4 million due to minor cervical abnormalities detected by the current cervical screening practice. The extensive opportunistic Pap testing fails to keep the incidence of cervical cancer from increasing among women aged 30-34. In addition opportunistic screening among this and younger age group detects a significant number of cytological abnormalities, most of which are probably treated unnecessarily.