RESUMO
BACKGROUND: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms. METHODS: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis. RESULTS: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (Ptrend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (Ptrend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer. CONCLUSIONS: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines.
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Dieta , Flavonoides , Humanos , Feminino , Flavonoides/administração & dosagem , Estudos Prospectivos , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias da Próstata/prevenção & controle , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/sangue , Modelos de Riscos Proporcionais , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/sangue , Estresse Oxidativo/efeitos dos fármacos , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/prevenção & controle , Neoplasias da Glândula Tireoide/sangue , Neoplasias/prevenção & controle , Neoplasias/epidemiologia , Reino Unido/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types. METHODS: This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene. RESULTS: SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31-0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42-0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42-0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70-1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects. CONCLUSION: SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.
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Neoplasias da Mama , Moduladores Seletivos de Receptor Estrogênico , Humanos , Feminino , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Estudos Retrospectivos , Cloridrato de Raloxifeno/uso terapêutico , Incidência , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/prevenção & controle , Indóis/uso terapêuticoAssuntos
Terapia de Reposição de Estrogênios , Menopausa , Intervenção Psicossocial , Disfunções Sexuais Fisiológicas , Disfunções Sexuais Psicogênicas , Feminino , Humanos , Pessoa de Meia-Idade , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Histerectomia/efeitos adversos , Libido/efeitos dos fármacos , Menopausa/efeitos dos fármacos , Menopausa/psicologia , Menorragia/cirurgia , Neoplasias Ovarianas/prevenção & controle , Prevalência , Intervenção Psicossocial/métodos , Salpingo-Ooforectomia/efeitos adversos , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/terapia , Disfunções Sexuais Psicogênicas/epidemiologia , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapiaRESUMO
INTRODUCTION: Established personal and familial risk factors contribute collectively to a woman's risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to investigate these risks but recent information on the role of common genomic variants, in the form of a Polygenic Risk Score (PRS), has provided the potential to further personalise breast and ovarian cancer risk assessment. Data from cohort studies support the potential of an integrated risk assessment to improve targeted risk management but experience of this approach in clinical practice is limited. METHODS AND ANALYSIS: The polygenic risk modification trial is an Australian multicentre prospective randomised controlled trial of integrated risk assessment including personal and family risk factors with inclusion of breast and ovarian PRS vs standard care. The study will enrol women, unaffected by cancer, undergoing predictive testing at a familial cancer clinic for a pathogenic variant in a known breast cancer (BC) or ovarian cancer (OC) predisposition gene (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D). Array-based genotyping will be used to generate breast cancer (313 SNP) and ovarian cancer (36 SNP) PRS. A suite of materials has been developed for the trial including an online portal for patient consent and questionnaires, and a clinician education programme to train healthcare providers in the use of integrated risk assessment. Long-term follow-up will evaluate differences in the assessed risk and management advice, patient risk management intentions and adherence, patient-reported experience and outcomes, and the health service implications of personalised risk assessment. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committee of Peter MacCallum Cancer Centre and at all participating centres. Study findings will be disseminated via peer-reviewed publications and conference presentations, and directly to participants. TRIAL REGISTRATION NUMBER: ACTRN12621000009819.
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Neoplasias da Mama , Predisposição Genética para Doença , Testes Genéticos , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Medição de Risco/métodos , Testes Genéticos/métodos , Estudos Prospectivos , Austrália , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Herança Multifatorial , Fatores de Risco , Adulto , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Ovarian cancer is an aggressive malignancy and the leading cause of death among gynecologic cancers. Researchers have evaluated prophylactic medications that potentially avert the manifestation of ovarian cancer, but currently, there are no reliable screening measures for this disease. Nevertheless, the largest study involving aspirin use and ovarian cancer reported a substantive risk reduction from enduring aspirin use. Since there are countervailing data to impugn the potential benefits of aspirin use in staving off ovarian cancer, further research should scrutinize the use of this medication as a prophylactic intervention, especially in women who are at higher risk for developing the disease.
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Aspirina , Neoplasias Ovarianas , Humanos , Aspirina/uso terapêutico , Feminino , Neoplasias Ovarianas/prevenção & controle , Fatores de Risco , Anti-Inflamatórios não Esteroides/uso terapêuticoRESUMO
Purpose: Breastfeeding is associated with numerous short- and long-term neonatal and maternal health benefits. Specifically, in BRCA1/2 female carriers, breastfeeding has been shown to reduce the considerably increased risks of breast and ovarian cancer. Nevertheless, there is paucity of data referring to the recommended postpartum surveillance of BRCA1/2 carriers. The purpose of this study was to evaluate the recommendations of health professionals regarding breastfeeding in BRCA carriers. Methods: This cross-sectional survey was conducted using an anonymous questionnaire distributed through the "Good BRCA Genes-a support and information group for BRCA carriers" association. The questionnaire included Likert scale and open-ended questions, aimed to evaluate the performance of health professionals at various aspects of the recommended follow-up. Results: Of the 388 participants, 233 (60.0%) expressed dissatisfaction with explanations provided by health professionals regarding pregnancy and breastfeeding. Women reporting dissatisfaction with explanations were younger (36.8 ± 7.0 years) compared to those satisfied with the explanations (38.8 ± 7.6 years, p = 0.0081). No significant differences were noted between women satisfied and those dissatisfied with the explanations in terms of age of genetic diagnosis, origin, religion, geographic location, and the rates of personal or familial cancer history. Of the 175 responses to an open question "please describe the reasons for unsatisfactory explanation," 76.6% stated they received no explanation on the subject, whereas 5.4% described minimal explanation or conflicting recommendations. Surprisingly, 4.7% recalled being advised to avoid, stop, or limit breastfeeding. Discussion: The results of this survey emphasize the lack of knowledge of health professionals on the issue of breastfeeding in BRCA carriers. As genetic variants in these genes involve significant proportion of the population (up to 2.5% in Ashkenazi Jewish population), raising the awareness of health care personnel to the benefits of breastfeeding in these women seems prudent.
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Aleitamento Materno , Neoplasias da Mama , Pessoal de Saúde , Humanos , Feminino , Aleitamento Materno/psicologia , Estudos Transversais , Adulto , Inquéritos e Questionários , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Pessoal de Saúde/psicologia , Gravidez , Heterozigoto , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Proteína BRCA1/genética , Genes BRCA2 , Genes BRCA1 , Predisposição Genética para Doença , Proteína BRCA2/genética , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em SaúdeAssuntos
Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/prevenção & controle , Testes Genéticos/métodos , Testes Genéticos/normas , Predisposição Genética para DoençaRESUMO
Kidney transplantation offers recipients superior outcomes and improved quality of life compared with dialysis. However, the need for ongoing immunosuppression places recipients at increased risk of certain forms of cancer. Screening and early detection of precancerous lesions are one of the few proven ways to lower the risk of cancer morbidity and mortality in the transplant population. Women have additional barriers to cancer screening services globally, especially in low- and middle-income countries as well as within certain disadvantaged groups in high-income countries. There is a dearth of published data on screening guidelines and policies on post-transplant malignancy in female recipients. It is vital that health care providers and patients are educated regarding the risks of cancer at all post-transplant stages and that the recommended screening policies are adhered to in order to reduce associated morbidity and mortality in this at-risk group.
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Detecção Precoce de Câncer , Acessibilidade aos Serviços de Saúde , Transplante de Rim , Humanos , Feminino , Neoplasias/prevenção & controle , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/diagnóstico , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Programas de Rastreamento/métodos , Saúde GlobalRESUMO
OBJECTIVES: To assess the association of socioeconomic demographics with recommendation for and uptake of risk-reducing bilateral salpingo-oophorectomy (rrBSO) in patients with BRCA1 and BRCA2 (BRCA1/2) mutations. DESIGN: Retrospective cohort, semistructured qualitative interviews. SETTING AND PARTICIPANTS: BRCA1/2 mutation carriers at an urban, public hospital with a racially and socioeconomically diverse population. INTERVENTION: None. PRIMARY AND SECONDARY OUTCOMES: The primary outcomes were rate of rrBSO recommendation and completion. Secondary outcomes were sociodemographic variables associated with rrBSO completion. RESULTS: The cohort included 167 patients with BRCA1/2 mutations of whom 39% identified as black (n=65), 35% white (n=59) and 19% Hispanic (n=32). Over 95% (n=159) received the recommendation for age-appropriate rrBSO, and 52% (n=87) underwent rrBSO. Women who completed rrBSO were older in univariable analysis (p=0.05), but not in multivariable analysis. Completion of rrBSO was associated with residence in zip codes with lower unemployment and documented recommendation for rrBSO (p<0.05). All subjects who still received care in the health system (n=79) were invited to complete interviews regarding rrBSO decision-making, but only four completed surveys for a response rate of 5.1%. Themes that emerged included menopause, emotional impact and familial support. CONCLUSIONS: In this understudied population, genetic counselling and surrogates of financial health were associated with rrBSO uptake, highlighting genetics referrals and addressing social determinants of health as opportunities to improve cancer prevention and reduce health inequities. Our study demonstrates a need for more culturally centred recruiting methods for qualitative research in marginalised communities to ensure adequate representation in the literature regarding rrBSO.
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Hospitais Públicos , Neoplasias Ovarianas , Salpingo-Ooforectomia , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Hospitais Urbanos , Mutação , Genes BRCA1 , Genes BRCA2 , Fatores Socioeconômicos , Pesquisa Qualitativa , Proteína BRCA1/genética , Proteína BRCA2/genética , Predisposição Genética para DoençaRESUMO
INTRODUCTION: Less than half of eligible Black women are assessed for genetic risk and only 28% engage in recommended hereditary breast and ovarian cancer (HBOC) risk-reducing interventions. CHWs are trusted individuals that work as a liaison between health systems and the community to improve access to services and support cancer prevention efforts, though they are an overlooked resource to support genetic risk assessment. To address the need and training gaps for CHWs, we developed and assessed an online training program to build CHW's competencies in cancer genomics and use of health information technologies to navigate high-risk individuals to appropriate genetic services. METHODS: The curriculum and 10 training modules were developed through engaging a panel of experts in a three-round Delphi process. Recruitment focused on CHWs who worked in clinical settings or groups providing outreach or health services to Black women. We assessed: changes in knowledge and attitudes about HBOC and genomics, as well as the perceptions about the quality and implementation of the training. RESULTS: Forty-six individuals expressed interest in the training after recruitment. Thirty eight individuals were eligible for the training and 26 completed the course. We found improvements in knowledge and genomics competencies immediately post-course, but the majority of these improvements were not sustained at 3-month follow-up. The training was highly rated for its relevance to CHW work and overall delivery. Top rated sessions included HBOC overview and family history collection. On average, participants reported discussing HBOC with 17 individuals at 3-month follow-up. CONCLUSION: Championing a diverse cancer and genomics workforce can help address the goals of the National Cancer Plan to improve early detection and health equity. Through this training, CHWs gained critical cancer and genomics knowledge that was then applied to their primary roles.
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Agentes Comunitários de Saúde , Genômica , Humanos , Feminino , Agentes Comunitários de Saúde/educação , Genômica/educação , Genômica/métodos , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama/genética , Currículo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/genética , Masculino , Competência ClínicaRESUMO
The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted primary disease prevention through intensive cancer surveillance, chemoprevention and risk-reducing surgery, reducing morbidity and preventing mortality. Cascade testing has been designated by the Centers for Disease Control and Prevention as a Tier 1 genomic application for hereditary breast and ovarian cancer. In this manuscript we describe a cascade genetic testing and in particular focus on its potential to provide necessary care to medically underserved and vulnerable populations.
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Predisposição Genética para Doença , Testes Genéticos , Humanos , Feminino , Medicina de Precisão/métodos , Mutação em Linhagem Germinativa , Aconselhamento Genético , Neoplasias/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias da Mama/genéticaRESUMO
OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.
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Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Salpingo-Ooforectomia , Humanos , Feminino , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias das Tubas Uterinas/prevenção & controle , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/prevenção & controle , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/prevenção & controle , Adulto , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Mutação em Linhagem Germinativa , Genes BRCA2 , Proteína BRCA2/genética , Proteína BRCA1/genética , Genes BRCA1RESUMO
More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.
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Vacinas Anticâncer , Ácidos Hidroxâmicos , Neoplasias Ovarianas , Animais , Feminino , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/prevenção & controle , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Ratos , Ácidos Hidroxâmicos/uso terapêutico , Ácidos Hidroxâmicos/farmacologia , Citometria de Fluxo , Linhagem Celular Tumoral , Modelos Animais de DoençasRESUMO
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.
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Anticoncepção , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , Anticoncepção/métodos , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/epidemiologia , Gravidez , Neoplasias do Endométrio/prevenção & controle , Neoplasias do Endométrio/epidemiologia , Doença Trofoblástica Gestacional/prevenção & controle , Doença Trofoblástica Gestacional/epidemiologia , Neoplasias dos Genitais Femininos/prevenção & controle , Fatores de RiscoRESUMO
BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.
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Neoplasias da Mama , Análise Custo-Benefício , Triagem de Portadores Genéticos , Testes Genéticos , Cadeias de Markov , Humanos , Feminino , Gravidez , Triagem de Portadores Genéticos/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/diagnóstico , Testes Genéticos/economia , Testes Genéticos/métodos , Anos de Vida Ajustados por Qualidade de Vida , Adulto , Técnicas de Apoio para a Decisão , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Genes BRCA1 , Diagnóstico Pré-Natal/economia , Diagnóstico Pré-Natal/métodos , Pessoa de Meia-Idade , Proteína BRCA1/genética , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodosRESUMO
PURPOSE: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care. METHODS: Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. Outcomes included rates of completion of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and NCCN risk-reducing and age-dependent screening guidelines (version 3.2019). Multivariable logistic regression analyses were used to evaluate potential predictors of these outcomes. RESULTS: Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) underwent RRSO and 77 (60%) had RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. Women with a history of breast or ovarian cancer were more likely to have RRM (OR = 4.38; 95% CI 1.80-11.51; p = 0.002). Increasing age was associated with an increased likelihood of RRSO (OR = 1.05; 95% CI 1.01-1.09; p = 0.019) and decreased likelihood for RRM (OR = 0.95; 95% CI 0.92-0.99; p = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 2.81; 95% CI 1.10-7.44; p = 0.025). Women who had genetic testing after June 2013 were less likely to have RRM than those tested before June 2013 (OR = 0.42; 95% CI 0.18-0.95; p = 0.040. None of the other measured factors were associated with rates of RRSO, RRM or follow through with NCCN recommendations. There was near universal (127/129) reported disclosure of genetic test results to family members, resulting in the discovery of a median of 1 relative with a pathogenic variant (range = 0-8). CONCLUSION: An evaluation of follow up practice in a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of reported completion of screening and surgical risk-reducing recommendations. Educational efforts should continue to reinforce the importance of follow-through with guideline recommended care among this high-risk group.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Testes Genéticos , Síndrome Hereditária de Câncer de Mama e Ovário , Humanos , Feminino , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Pessoa de Meia-Idade , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Detecção Precoce de Câncer , Predisposição Genética para Doença , Idoso , Comportamento de Redução do Risco , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Mutação , Salpingo-OoforectomiaRESUMO
BACKGROUND: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. METHODS: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC]). RESULTS: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14â160-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100â000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37â500-50â000 per arm, depending on assumptions concerning control-arm test-positives. CONCLUSIONS: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.
Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Neoplasias Pulmonares , Programas de Rastreamento , Neoplasias da Próstata , Humanos , Detecção Precoce de Câncer/métodos , Feminino , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Masculino , Tamanho da Amostra , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Programas de Rastreamento/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/prevenção & controle , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/prevenção & controle , Sangue Oculto , Projetos de Pesquisa , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/mortalidade , Pessoa de Meia-Idade , Ensaios Clínicos como Assunto , Minnesota/epidemiologia , Idoso , Estados Unidos/epidemiologiaRESUMO
Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316â882 women with surgical treatment for ectopic pregnancy and 3â168â820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.
Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Gravidez Ectópica , Salpingectomia , Humanos , Feminino , Gravidez , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/epidemiologia , Adulto , Taiwan/epidemiologia , Gravidez Ectópica/epidemiologia , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/epidemiologia , Incidência , Estudos de Casos e Controles , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
PURPOSE: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness. METHODS: We conducted group discussions with young women (aged 21-40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended. FINDINGS: Key themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts. CONCLUSION: Young women see pragmatic opportunities for health systems to optimize HBOC screening implementation.