The Current State-or Lack Thereof-of Screening and Prevention for Gynecologic Malignancies for Patients With Lynch Syndrome.

Lynch syndrome (LS) is an autosomal dominant genetic disorder that results in an increased risk of ovarian and endometrial cancers. The aim of this paper was to explore the management of this risk through screening and prevention. Published materials and evidence were explored and summarized. This paper demonstrated that while there has been increased awareness and advances in the identification and diagnosis of patients with LS, recommendations for screening and prevention remain less evidence-based. In decisions of management of patients with LS, a shared decision-making model should be used considering individual patient goals.

Fraction of cancers attributable to and prevented by reproductive factors and exogenous hormones use in Italy.

OBJECTIVE: Endogenous and exogenous hormonal factors have been associated with female breast, genital, and colorectal cancer risk. The aim of the present study is to conduct an evidence-based evaluation of the fraction of cancers attributable to and prevented by exogenous hormonal (i.e., combined oral contraceptives [COC] and combined estrogen-progestogen menopausal therapy [CEPMT]) and reproductive factors (i.e., parity and breastfeeding) in Italy. STUDY DESIGN: We calculated the population attributable and prevented fractions combining relative risks and prevalence of exposure in Italian women. Italian cancer incidence and mortality data were extracted from national sources and used to estimate the number of cancer cases and deaths attributable to reproductive factors and exogenous hormones in Italy in 2020. For long-term effects, a 20-year latency period was considered. RESULTS: COC were responsible for 4.4 % of breast and 10.9 % of cervical cancers in women aged 15-44, but also avoided 6.4 % of endometrial, 5.6 % of ovarian, and 2.9 % of colorectal cancers in women of all ages. Overall, COC use prevented 1174 cancer diagnoses and 577 cancer deaths. CEPMT caused 0.4 % of breast cancers at age 45-69. Low parity accounted for 8.1 %, 11.8 % and 15.5 % of breast, endometrial and ovarian cancers, respectively (6267 cases, 1796 deaths). Breastfeeding avoided 6.4 % of breast cancers (3775 cases, 897 deaths). CONCLUSIONS: Our analysis quantified the complex effects of hormonal and reproductive factors on cancer burden in Italian women.

Contraceptive strategies for reducing the risk of reproductive cancers.

Reproductive cancers, encompassing various malignancies like endometrial, ovarian, cervical cancer, and gestational trophoblastic neoplasia, pose a significant global health burden. Understanding their patterns is vital for effective prevention and management. Contraceptives show a protective effect against some of these cancers. This clinical guidance document aims to elucidate the disease burden of reproductive cancers and the evidence supporting contraceptive methods in prevention and management. Regional disparities in incidence and mortality highlight the urgent need for targeted interventions, particularly in low-resource settings. Healthcare providers must weigh individual risk profiles and medical eligibility criteria when discussing contraceptive options. Enhanced health literacy through direct patient education is essential for leveraging low-cost behavioral interventions to mitigate reproductive cancer risks.

Approaches to prevention of gynecological malignancies.

Gynecological malignancies represent one of the prevalent diseases in the female sex and prevention is essential to limit their incidence and mortality. Nowadays, not all malignancies benefit from adequate screening methods for this reason new biomarkers and methods are being developed to undertake timely and effective therapies.

How far is too far? Cancer prevention and clinical trial enrollment in geographically underserved patient populations.

Despite dedicated efforts to improve equitable access to cancer care in the United States, disparities in cancer outcomes persist, and geographically underserved patients remain at an increased risk of cancer with lower rates of survival. The critical evaluation of cancer prevention inequities and clinical trial access presents the opportunity to outline novel strategies to incrementally improve bookended access to gynecologic cancer care for geographically underserved patients. Cancer prevention strategies that can be addressed in the rural patient population mirror priorities in the Healthy People 2030 objectives and include increased identification of high risk individuals who may benefit from increased cancer screening and risk reduction, increasing the proportion of people who discuss interventions to prevent cancer, such as HPV vaccination, with their provider, and increasing the proportion of adults who complete evidence based cancer screening. Barriers to accrual to clinical trials for rural patients overlap significantly with the same barriers to obtaining health care in general. These barriers include: lack of facilities and specialized providers; lack of robust health infrastructure; inability to travel; and financial barriers. In this review, we will discuss current knowledge and opportunities to improve cancer prevention initiatives and clinical trial enrollment in geographically underserved populations with a focus on rurality.

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.

Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement.

Female genital tract (FGT) microbiota has been associated with the development of gynaecological cancers. Thus, the possibility of whether manipulation of the FGT microbiota can help in the prevention of disease should be investigated. Various prebiotics, probiotics, and other non-clinician prescribed agents have been reported to have therapeutic effects in cervical disease. Numerous studies have reported an association between human papillomavirus infection and subsequent cervical dysplasia and a decrease in the abundance of Lactobacillus species. A continuum of microbiota composition is observed from the vagina to the upper parts of the FGT, but no evidence suggests that manipulation of the vaginal microbiota can help to modify the composition of other FGT compartments. Although prebiotics and probiotics have been reported to be beneficial, the studies are small and of varying design, and high-quality evidence to support their use is lacking. Currently, no studies have examined these therapeutics in other gynaecological malignancies. Thus, recommendation of probiotics, prebiotics, or other over-the-counter supplements for the prevention of gynaecological cancers warrants larger, well designed studies.

Executive Summary of the Lower Anogenital Tract Cancer Evidence Review Conference.

The Centers for Disease Control and Prevention sponsored a project conducted by the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. For this final module, focusing on the cancers of the lower anogenital tract (vulva, vagina, and anus), a panel of experts in evidence assessment from the Society for Academic Specialists in General Obstetrics and Gynecology, ASCCP, and the Society of Gynecologic Oncology reviewed relevant literature and current guidelines. Panel members conducted structured literature reviews, which were then reviewed by other panel members. Representatives from stakeholder professional and patient advocacy organizations met virtually in September 2022 to review and provide comment. This article is the executive summary of the review. It covers prevention, early diagnosis, and special considerations of lower anogenital tract cancer. Knowledge gaps are summarized to provide guidance for future research.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Association between Different Types of Tea Consumption and Risk of Gynecologic Cancer: A Meta-Analysis of Cohort Studies.

Plenty of studies have shown that tea has an effect of inhibiting gynecologic tumors. However, there still remained controversy of the association between tea and gynecologic tumors in epidemiological studies. In this study, PubMed, Embase, and Cochrane Database were used to search the literature from 1 January 1960 to 26 December 2022 to investigate the association between tea intake and gynecologic cancer risk. In total, 19 cohort studies with 2,020,980 subjects and 12,155 gynecological tumor cases were retrieved. The pooled relative risk (RR) of gynecologic tumor for tea intake was 1.00 (95% CI: 0.96-1.04). RRs were 0.94 (95% CI: 0.88-1.01) for ovarian cancer, 1.02 (95% CI: 0.97-1.07) for endometrial cancer, and 1.06 (95% CI: 0.91-1.23) for cervical cancer. Subgroup analyses were adopted based on the tea type and geographic location. Interestingly, significant preventive impact of non-herbal tea on ovarian cancer (pooled relative risk: 0.67; 95% CI: 0.55-0.81) was found, especially for black tea (pooled relative risk: 0.64; 95% CI: 0.51-0.80). Dose-response analysis indicated that although it is not statistically significant, a decreasing trend of ovarian cancer risk could be observed when the tea consumption was 1.40 to 3.12 cups/day. In conclusion, our findings suggested that ovarian cancer, but not other gynecologic cancers, could possibly be prevented by drinking non-herbal tea. In addition, the preventive impact of green tea on gynecologic cancer seemed to be relatively weak and needs further cohorts to validate it.

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.

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention.

Individuals with proven hereditary cancer syndrome (HCS) such as BRCA1 and BRCA2 have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk. In response to this unmet opportunity for prevention, the British Columbia Gynecologic Cancer Initiative convened a research summit "Gynecologic Cancer Prevention: Thinking Big, Thinking Differently" in Vancouver, Canada on 26 November 2021. The aim of the conference was to explore how hereditary cancer prevention via population-based genetic testing could decrease morbidity and mortality from gynecologic cancer. The summit invited local, national, and international experts to (1) discuss how genetic testing could be more broadly implemented in a Canadian system, (2) identify key research priorities in this topic and (3) outline the core essential elements required for such a program to be successful. This report summarizes the findings from this research summit, describes the current state of hereditary genetic programs in Canada, and outlines incremental steps that can be taken to improve prevention for high-risk Canadians now while developing an organized population-based hereditary cancer strategy.

Association between statin use and the risk, prognosis of gynecologic cancer: A meta-analysis.

BACKGROUND: Recent evidence has demonstrated that the salutary effect of statins on the prevention and prognosis of cancers, including gynecologic cancers. However, due to the heterogeneity of tumors, the results from related studies regarding the association between statin therapy and gynecologic cancers are conflicting. Thus, we conducted this meta-analysis to better understand the relationship between statins use and gynecologic cancers. METHODS: We searched for articles published before July 2021 in the databases: PubMed, Web of Science, Medline, EMBASE and Google Scholar. We computed odds ratio (OR)/relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CI) regarding the association between statin use and the risk or prognosis of gynecologic cancers by using STATA 12.0 software. RESULTS: The present meta-analysis showed that statin use was associated with a lower risk of gynecologic cancer (OR/RR = 0.89, 95% CI 0.83 to 0.96, I2 = 60.6%, p < 0.001). Statin use was associated with lower risks of endometrial cancer and ovarian cancer (endometrial cancer: OR/RR = 0.81, 95% CI 0.70 to 0.94, I2 = 62.3%, p = 0.001; ovarian cancer: OR/RR = 0.92, 95% CI 0.85 to 1.00, I2 = 42.1%, p = 0.077). The present meta-analysis showed that statin use was associated with a lower mortality of gynecologic cancer (HR = 0.73, 95% CI 0.67 to 0.80, I2 = 39.0%, p = 0.03). Statin use was associated with lower mortalities of endometrial cancer and ovarian cancer (endometrial cancer: HR = 0.71, 95% CI 0.64 to 0.80, I2 = 31.9%, p = 0.144; ovarian cancer: HR = 0.78, 95% CI 0.73 to 0.83, I2 = 43.9%, p = 0.051). CONCLUSION: Statins use was inversely associated with the risk and mortality of gynecologic cancers. Meanwhile, we need more well-designed and high-quality studies with strong evidence for definite conclusions that determine clinical practice.

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.

Awareness about Gynecologic Cancers and Related Factors among Healthy Women: A Cross-Sectional Study.

The risk of cancer-related mortality and morbidity decreases when women are aware of the risk factors for gynecologic cancers and implement strategies such as attending relevant early screening programs. This cross-sectional study conducted between August 2017 and August 2018 at a public hospital in Turkey aimed to determine the awareness about gynecologic cancers among healthy women by utilized the Krieger's ecosocial theory as a framework for the study. The study included 554 Turkish women aged 18-65 years. Data were collected using the Gynecological Cancer Awareness Scale (GCAS) and a questionnaire designed in this study. Significant differences were noted between the average GCAS score and variables such as the amount of menstrual bleeding, entering menopause, a history of reproductive system disease, regular gynecological examination (including Pap test), regular vaginal self-examination, sexually transmitted infections (STIs), genital hygiene behavior, the fear of having cancer, having knowledge about cancer, and requiring information about cancer (p < .05). Despite the high level of awareness about gynecologic cancer among these women, the lack of proper knowledge and preventive measures was high. Having knowledge about gynecologic cancers results in increased awareness; however, the level of knowledge is not sufficient to prevent gynecologic cancers, which shows the need for sufficient and effective cancer screening and education programs.

Trends in oral contraceptive and intrauterine device use among reproductive-aged women in the US from 1999 to 2017.

PURPOSE: Since the 1960s, increasing oral contraceptive (OC) use has mirrored decreasing ovarian cancer incidence. The impact of intrauterine devices (IUDs) on cancer risk is less well established. With improved access and increased options, we must consider how changing usage can affect cancer risks. METHODS: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES, 1999-2016) and the National Survey for Family Growth (NSFG, 2006-2017) were used to evaluate contraceptive use over time in premenopausal women (NHANES n = 13,179; NSFG n = 26,262). Trends were assessed overall and by race, age, pregnancy history, education, and body mass index. RESULTS: The average annual absolute increase in self-reported IUD use was 0.81% (NSFG), while OC use decreased 0.49% in NSFG and 0.47% in NHANES. This represents a significant decrease in OC use in NSFG [annual percent change (APC) - 2.2% (95% CI - 3.4, - 1.0%), p < 0.01]. Trends in OC use varied somewhat by pregnancy history in NHANES (p-interaction = 0.054). In contrast, IUD use increased 6.2% annually [(1.4, 11.2%), p = 0.03] and varied significantly by pregnancy history (p-interaction < 0.01). Nulligravid women increased IUD use 11.0% annually [(2.6, 20.1%), p = 0.02] compared to women with prior pregnancy at 5.2% [(0.4, 10.2%), p = 0.04]. In 2015-2017, IUD use was 76.5% hormonal (71.1, 81.8%) and 22.9% copper (17.4, 28.3%) with greater hormonal IUD use in obese women [89.4%, (82.9, 95.9%)]. CONCLUSION: Increasing IUD use outpaced declining OC use in premenopausal US women. There may be a resulting decreased gynecologic cancer risk as more women gain access to potentially risk-reducing contraceptives.

Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

PURPOSE: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years. RESULTS: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. CONCLUSION: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes.

Phytochemicals in Gynecological Cancer Prevention.

Gynecological cancer confers an enormous burden among women worldwide. Accumulating evidence points to the role of phytochemicals in preventing cervical, endometrial, and ovarian cancer. Experimental studies emphasize the chemopreventive and therapeutic potential of plant-derived substances by inhibiting the early stages of carcinogenesis or improving the efficacy of traditional chemotherapeutic agents. Moreover, a number of epidemiological studies have investigated associations between a plant-based diet and cancer risk. This literature review summarizes the current knowledge on the phytochemicals with proven antitumor activity, emphasizing their effectiveness and mechanism of action in gynecological cancer.