RESUMO
BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Estudos Retrospectivos , Proteína BRCA1/genética , Proteína BRCA2/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Prognóstico , Intervalo Livre de Doença , Adulto Jovem , Mutação em Linhagem Germinativa , Heterozigoto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ftalazinas/efeitos adversos , Células Germinativas/patologia , Proteína BRCA1/genéticaRESUMO
We investigated intestinal trichomonads in western lowland gorillas, central chimpanzees and humans cohabiting the forest ecosystem of Dzanga-Sangha Protected Area in Central African Republic, using the internal transcribed spacer (ITS) region and SSU rRNA gene sequences. Trichomonads belonging to the genus Tetratrichomonas were detected in 23% of the faecal samples and in all host species. Different hosts were infected with different genotypes of Tetratrichomonas. In chimpanzees, we detected tetratrichomonads from 'novel lineage 2', which was previously reported mostly in captive and wild chimpanzees. In gorillas, we found two different genotypes of Tetratrichomonas. The ITS region sequences of the more frequent genotype were identical to the sequence found in a faecal sample of a wild western lowland gorilla from Cameroon. Sequences of the second genotype from gorillas were almost identical to sequences previously obtained from an anorexic French woman. We provide the first report of the presence of intestinal tetratrichomonads in asymptomatic, apparently healthy humans. Human tetratrichomonads belonged to the lineage 7, which was previously reported in domestic and wild pigs and a domestic horse. Our findings suggest that the ecology and spatial overlap among hominids in the tropical forest ecosystem has not resulted in exchange of intestinal trichomonads among these hosts.
Assuntos
Doenças dos Símios Antropoides/parasitologia , Gorilla gorilla/parasitologia , Pan troglodytes/parasitologia , Infecções Protozoárias em Animais/parasitologia , Infecções por Protozoários/parasitologia , Trichomonadida/classificação , Animais , Doenças dos Símios Antropoides/epidemiologia , República Centro-Africana/epidemiologia , Fezes/parasitologia , Especificidade de Hospedeiro , Humanos , Filogenia , Infecções por Protozoários/epidemiologia , Infecções Protozoárias em Animais/epidemiologiaAssuntos
Neoplasias da Mama , Síndromes Neoplásicas Hereditárias , Neoplasias Ovarianas , Humanos , Feminino , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Comportamento de Redução do Risco , Predisposição Genética para DoençaRESUMO
BACKGROUND: Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is a risk prediction algorithm that can be used to compute estimates of age-specific risk of breast cancer. It is uncertain whether BOADICEA performs adequately for populations outside the United Kingdom. METHODS: Using a batch mode version of BOADICEA that we developed (BOADICEACentre), we calculated the cumulative 10-year invasive breast cancer risk for 4176 Australian women of European ancestry unaffected at baseline from 1601 case and control families in the Australian Breast Cancer Family Registry. Based on 115 incident breast cancers, we investigated calibration, discrimination (using receiver-operating characteristic (ROC) curves) and accuracy at the individual level. RESULTS: The ratio of expected to observed number of breast cancers was 0.92 (95% confidence interval (CI) 0.76-1.10). The E/O ratios by subgroups of the participant's relationship to the index case and by the reported number of affected relatives ranged between 0.83 and 0.98 and all 95% CIs included 1.00. The area under the ROC curve was 0.70 (95% CI 0.66-0.75) and there was no evidence of systematic under- or over-dispersion (P=0.2). CONCLUSION: BOADICEA is well calibrated for Australian women, and had good discrimination and accuracy at the individual level.
Assuntos
Neoplasias da Mama/epidemiologia , Simulação por Computador , Modelos Estatísticos , Adulto , Idoso , Algoritmos , Austrália , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Saúde da Família , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: This report prospectively examines the 4-year course, and predictors of course, of body dysmorphic disorder (BDD), a common and often severe disorder. No prior studies have prospectively examined the course of BDD in individuals ascertained for BDD. Method The Longitudinal Interval Follow-Up Evaluation (LIFE) assessed weekly BDD symptoms and treatment received over 4 years for 166 broadly ascertained adults and adolescents with current BDD at intake. Kaplan-Meier life tables were constructed for time to remission and relapse. Full remission was defined as minimal or no BDD symptoms, and partial remission as less than full DSM-IV criteria, for at least 8 consecutive weeks. Full relapse and partial relapse were defined as meeting full BDD criteria for at least 2 consecutive weeks after attaining full or partial remission respectively. Cox proportional hazards regression examined predictors of remission and relapse. RESULTS: Over 4 years, the cumulative probability was 0.20 for full remission and 0.55 for full or partial remission from BDD. A lower likelihood of full or partial remission was predicted by more severe BDD symptoms at intake, longer lifetime duration of BDD, and being an adult. Among partially or fully remitted subjects, the cumulative probability was 0.42 for subsequent full relapse and 0.63 for subsequent full or partial relapse. More severe BDD at intake and earlier age at BDD onset predicted full or partial relapse. Eighty-eight percent of subjects received mental health treatment during the follow-up period. CONCLUSIONS: In this observational study, BDD tended to be chronic. Several intake variables predicted greater chronicity of BDD.
Assuntos
Transtornos Dismórficos Corporais/psicologia , Progressão da Doença , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Transtornos Dismórficos Corporais/terapia , Doença Crônica , Delusões/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Psicoterapia/estatística & dados numéricos , Psicotrópicos/uso terapêutico , Recidiva , Indução de RemissãoRESUMO
BACKGROUND: Fertility is a priority for many young women with breast cancer. Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions. This study aimed to prospectively evaluate the efficacy of a fertility-related decision aid (DA). METHODS: A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics, aged 18-40 years and desired future fertility, were assessed on decisional conflict, knowledge, decision regret, and satisfaction about fertility-related treatment decisions. These were measured at baseline, 1 and 12 months, and were examined using linear mixed effects models. RESULTS: Compared with usual care, women who received the DA had reduced decisional conflict (ß=-1.51; 95%CI: -2.54 to 0.48; P=0.004) and improved knowledge (ß=0.09; 95%CI: 0.01-0.16; P=0.02), after adjusting for education, desire for children and baseline uncertainty. The DA was associated with reduced decisional regret at 1 year (ß=-3.73; 95%CI: -7.12 to -0.35; P=0.031), after adjusting for education. Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility (P<0.001), fertility options (P=0.005), and rated it more helpful (P=0.002), than those who received standard care. CONCLUSION: These findings support widespread use of this DA shortly after diagnosis (before chemotherapy) among younger breast cancer patients who have not completed their families.
Assuntos
Neoplasias da Mama/patologia , Técnicas de Apoio para a Decisão , Preservação da Fertilidade , Adulto , Ansiedade , Neoplasias da Mama/psicologia , Conflito Psicológico , Tomada de Decisões , Depressão , Emoções , Feminino , Humanos , Estadiamento de Neoplasias , Educação de Pacientes como Assunto , Satisfação do Paciente , Estudos Prospectivos , Encaminhamento e Consulta , Inquéritos e QuestionáriosRESUMO
BACKGROUND: In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). METHODS: One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. RESULTS: Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. CONCLUSION: Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.
Assuntos
Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cognição/efeitos dos fármacos , Antagonistas de Estrogênios/efeitos adversos , Nitrilas/efeitos adversos , Tamoxifeno/efeitos adversos , Triazóis/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Feminino , Humanos , Letrozol , Estadiamento de Neoplasias , Qualidade de VidaRESUMO
BACKGROUND: Knowing a young woman with newly diagnosed breast cancer has a germline BRCA1 mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data. METHODS: We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a BRCA1 mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation. RESULTS: The probability of being a BRCA1 mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (P<0.0001). From the most parsimonious multivariate model, the odds ratio for being a carrier were: 9.7 (95% confidence interval: 2.6-47.0) for trabecular growth pattern (P=0.001); 7.8 (2.7-25.7) for mitotic index over 50 mitoses per 10 high-powered field (P=0.0003); and 2.7 (1.3-5.9) for each first-degree relative with breast cancer diagnosed before age 60 years (P=0.01).The area under the ROC curve was 0.87 (0.83-0.90). CONCLUSION: Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all BRCA1 germline mutation carriers among women with early-onset breast cancer without taking into account family history.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/patologia , Genes BRCA1 , Mutação em Linhagem Germinativa , Adulto , Fatores Etários , Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Análise Mutacional de DNA , Saúde da Família , Feminino , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Carga Tumoral , MulheresRESUMO
Published studies have reached contradictory conclusions regarding breast cancer risk for women from families segregating a BRCA1 or BRCA2 mutation who do not carry the family-specific mutation. Accurate estimation of breast cancer risk is crucial for appropriate counselling regarding risk management. The aim of this study is to prospectively assess whether breast cancer risk for mutation negative women from families segregating BRCA1 or BRCA2 mutations is greater than for women in the general population. Eligible women were 722 first-, second- and third-degree relatives of a BRCA1 or BRCA2 mutation carrier from 224 mutation positive (128 BRCA1, 96 BRCA2) families, had no personal cancer history at baseline, and had been tested and found not to carry the family-specific mutation. Self-reported family history of cancer, preventive interventions and verified cancer diagnoses were collected at baseline, and every 3 years thereafter. Median follow-up was 6.1 years (range 0.1-12.4 years). Time at risk of breast cancer was censored at cancer diagnosis or risk-reducing surgery. Standardised incidence ratios (SIR) were estimated by comparing observed to population incidences of invasive breast cancer using Australian Cancer Incidence and Mortality Books. Six cases of invasive breast cancer were observed. The estimated SIRs were 1.14 (95% CI: 0.51-2.53) overall (n = 722), 1.29 (95% CI: 0.58-2.88) when restricted to first- and second-degree relatives of an affected mutation carrier (n = 442) and 0.48 (95% CI: 0.12-1.93) when restricted to those with no family history of breast cancer in the non-mutation carrying parental lineage (n = 424). There was no evidence that mutation negative women from families segregating BRCA1 or BRCA2 mutations are at increased risk of breast cancer. Despite this being the largest prospective cohort to assess this issue, moderately increased breast cancer risk (2-fold) cannot be ruled out.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Adulto JovemRESUMO
It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans.
Assuntos
Cebus , Cerebelo , Córtex Cerebral , Pan troglodytes , Adulto , Animais , Feminino , Masculino , Adulto Jovem , Evolução Biológica , Cebus/anatomia & histologia , Cerebelo/anatomia & histologia , Córtex Cerebral/anatomia & histologia , Imageamento por Ressonância Magnética , Vias Neurais , Pan troglodytes/anatomia & histologia , HumanosRESUMO
The distinction between normality and psychopathology has long been subject to debate. DSM-III and DSM-IV provided a definition of mental disorder to help clinicians address this distinction. As part of the process of developing DSM-V, researchers have reviewed the concept of mental disorder and emphasized the need for additional work in this area. Here we review the DSM-IV definition of mental disorder and propose some changes. The approach taken here arguably takes a middle course through some of the relevant conceptual debates. We agree with the view that no definition perfectly specifies precise boundaries for the concept of mental/psychiatric disorder, but in line with a view that the nomenclature can improve over time, we aim here for a more scientifically valid and more clinically useful definition.
Assuntos
Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos Mentais/diagnóstico , Terminologia como Assunto , Humanos , Transtornos Mentais/classificação , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , PsicopatologiaRESUMO
BACKGROUND: Personalised prevention of breast cancer has focused on women at very high risk, yet most breast cancers occur in women at average, or moderately increased risk (≤moderate risk). OBJECTIVES: To determine; 1) interest of women atâ¯≤â¯moderate risk (consumers) in personalised information about breast cancer risk; 2) familial cancer clinicians' (FCCs) perspective on managing women atâ¯≤â¯moderate risk, and; 3) both consumers' and FCCs reactions to iPrevent, a personalised breast cancer risk assessment and risk management decision support tool. METHODS: Seven focus groups on breast cancer risk were conducted with 49 participants; 27 consumers and 22 FCCs. Data were analysed thematically. RESULTS: Consumers reported some misconceptions, low trust in primary care practitioners for breast cancer prevention advice and frustration that they often lacked tailored advice about breast cancer risk. They expressed interest in receiving personalised risk information using iPrevent. FCCs reported an inadequate workforce to advise women atâ¯≤â¯moderate risk and reacted positively to the potential of iPrevent to assist. CONCLUSIONS: While highlighting a potential role for iPrevent, several outstanding issues remain. For personalised prevention of breast cancer to extend beyond women at high risk, we must harness women's interest in receiving tailored information about breast cancer prevention and identify a workforce willing to advise women.
Assuntos
Algoritmos , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Neoplasias da Mama/prevenção & controle , Técnicas de Apoio para a Decisão , Internet , Adulto , Idoso , Austrália , Feminino , Grupos Focais , Aconselhamento Genético , Pessoal de Saúde , Síndrome Hereditária de Câncer de Mama e Ovário , Humanos , Masculino , Pessoa de Meia-Idade , Oncologistas , Médicos de Atenção Primária , Medição de Risco , Adulto JovemRESUMO
OBJECTIVE: Describe the development, acceptability and feasibility of a Decision Aid (DA) for women with early-stage breast cancer (BC) at average contralateral breast cancer (CBC) risk considering contralateral prophylactic mastectomy (CPM). METHODS: The DA was developed using the International Patient Decision Aid Standards (IPDAS) and the Ottawa Decision Support Framework. It provides evidence-based information about CPM in a booklet format combining text, graphs and images of surgical options. Twenty-three women with a history of early-stage breast cancer were interviewed in person or over the phone using a 'think aloud approach'. Framework analysis was used to code and analyse data. RESULTS: Twenty-three women participated in the study. Mean age of participants was 58.6 years and time since diagnosis ranged from 14 months to 21 years. Five women had CPM and eighteen had not. Women strongly endorsed the DA. Many felt validated by a section on appearance and found information on average risk of recurrence and metastases helpful, however, noted the importance of discussing personal risk with their surgeon. Many requested more information on surgery details (time taken, recovery) and costs of the different options. CONCLUSION: The DA was acceptable to women, including the format, content and proposed implementation strategies. Practical and financial issues are important to women in considering treatment options. PRACTICE IMPLICATIONS: Women appreciate information about CPM at diagnosis and emphasised the importance of discussing potential downsides of the procedure in addition to benefits. The DA was considered acceptable to facilitate such discussions.
Assuntos
Neoplasias da Mama/psicologia , Tomada de Decisões , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/psicologia , Mastectomia Profilática/psicologia , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/psicologia , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Whether BRCA1 and BRCA2 mutation carriers have a clinically relevant elevated risk of uterine cancer has implications for risk-reducing surgery. AIM: This multicentre, prospective cohort study assessed uterine cancer risk for mutation carriers compared with the general population. METHODS: Eligible mutation carriers were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) cohort study, had a uterus present and no history of uterine cancer at cohort entry. Epidemiological, lifestyle and clinical data were collected at cohort entry and updated three-yearly. Cancer events were verified using pathology reports. Follow-up was censored at death or last contact. Relative risk of uterine cancer was estimated using the standardised incidence ratio (SIR), with the expected number of cases determined using population-based data for Australia. RESULTS: Of 1,111 mutation carriers in kConFab, 283 were excluded due to prior hysterectomy (N = 278), prior uterine cancer (N = 2) or being non-residents (N = 3). After a median follow-up of 9.0 years, five incident uterine cancers were reported in the 828 eligible women (419 had prior breast cancer and 160 had prior tamoxifen use), compared to 2.04 expected (SIR = 2.45; 95% confidence interval [CI]: 0.80-5.72; P = 0.11). In 438 BRCA1 mutation carriers and 390 BRCA2 mutation carriers, three and two incident cases of uterine cancer were reported, respectively, compared to 1.04 expected (SIR = 2.87; 95% CI: 0.59-8.43; P = 0.18) and 0.99 expected (SIR = 2.01; 95% CI: 0.24-7.30; P = 0.52), respectively. All cases were endometrioid subtype, International Federation of Gynaecology and Obstetrics stage I-II disease. No serous uterine cancers were reported. CONCLUSIONS: Our findings are consistent with those from most other reports and do not support routine risk-reducing hysterectomy for BRCA1 and BRCA2 mutation carriers.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Heterozigoto , Mutação , Neoplasias Uterinas/genética , Adulto , Austrália/epidemiologia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Histerectomia , Incidência , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Fenótipo , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Fatores de Tempo , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/prevenção & controleRESUMO
OBJECTIVES: The quality of risk-reducing salpingo-oophorectomy (RRSO) performed in Australasian women was previously reported to be suboptimal. Here we describe the quality of RRSO performed since 2008 in women enrolled in the same cohort and determine whether it has improved. DESIGN: Prospective cohort study of women at high risk of pelvic serous cancer (PSC) in kConFab. Eligible women had RRSO between 2008 and 2014 and their RRSO surgical and pathology reports were reviewed. "Adequate" surgery and pathology were defined as complete removal and paraffin embedding of all ovarian and extra-uterine fallopian tube tissue, respectively. Associations between clinical factors and "adequate" pathology were assessed using logistic regression. Data were compared with published cohort data on RRSO performed prior to 2008 using Chi square test. RESULTS: Of 164 contemporary RRSOs performed in 78 centres, 158/159 (99%) had "adequate" surgery and 108/164 (66%) had "adequate" pathology. Surgery performed by a gynaecologic oncologist rather than a general gynaecologist [OR 8.2, 95%CI (3.6-20.4), p < 0.001], surgery without concurrent hysterectomy [OR 2.5, 95%CI (1.1-6.0), p = 0.03], more recent year of surgery [OR 1.4, 95%CI (1.1-1.8), p = 0.02], and clinical notation that indicated high risk [OR 19.4, 95%CI (3.1-385), p = 0.008] were independently associated with "adequate" pathology. Both surgery and pathology were significantly more likely to be "adequate" (p < 0.001) in this contemporary sample. CONCLUSION: The quality of RRSOs has significantly improved since our last report. Surgery by a gynaecologic oncologist who informs the pathologist that the woman is at high risk for PSC is associated with optimal RRSO pathology.
Assuntos
Cistadenocarcinoma Seroso/cirurgia , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Ovarianas/cirurgia , Salpingo-Ooforectomia/métodos , Adulto , Idoso , Austrália , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Feminino , Genes BRCA1 , Genes BRCA2 , Heterozigoto , Humanos , Pessoa de Meia-Idade , Nova Zelândia , Oncologistas , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Procedimentos Cirúrgicos Profiláticos , Estudos Prospectivos , Qualidade da Assistência à Saúde , Fatores de RiscoRESUMO
PURPOSE: The use of chemotherapy and endocrine therapies in the treatment of premenopausal women carries with it reproductive and gynecologic implications that young women may find distressing and discordant with plans for childbearing. This multicenter study aimed to investigate fertility- and menopause-related information needs among young women with a diagnosis of early-stage breast cancer. PATIENTS AND METHODS: Two hundred twenty-eight women with a diagnosis of early-stage breast cancer who were aged 40 years or younger at diagnosis and who were 6 to 60 months after diagnosis were entered onto the trial. Participants completed a mailed self-report questionnaire that included a purposely designed fertility- and menopause-related information needs survey and standardized measures of distress, anxiety, quality of life, menopausal symptoms, and information-seeking style. RESULTS: Seventy-one percent of participants discussed fertility-related issues with a health professional as part of their breast cancer treatment, and 86% discussed menopause-related issues. Consultation with a fertility or menopause specialist was the most preferred method of obtaining this information. Receiving fertility-related information was rated as being significantly more important than receiving menopause-related information at time of diagnosis (P < .001) and at treatment decision making (P = .058). Receiving menopause-related information was rated as being significantly more important than receiving fertility-related information during adjuvant treatment (P < .05), at completion of adjuvant treatment (P < .001), and during follow-up (P < .001). Common questions, sources of information, and correlates of perceived importance were identified. CONCLUSION: The results of this study suggest that younger women have unmet needs for fertility- and menopause-related information and provide preliminary empirical data to guide the development of better fertility- and menopause-related patient education materials for younger women with a diagnosis of early breast cancer.
Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Fertilidade , Menopausa , Avaliação das Necessidades , Adulto , Idade de Início , Neoplasias da Mama/psicologia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Estadiamento de Neoplasias , Educação de Pacientes como Assunto , Qualidade de Vida , Estresse PsicológicoRESUMO
DSM-IV's classification of body dysmorphic disorder (BDD) is controversial. Whereas BDD is classified as a somatoform disorder, its delusional variant is classified as a psychotic disorder. However, the relationship between these BDD variants has received little investigation. In this study, we compared BDD's delusional and nondelusional variants in 191 subjects using reliable and valid measures that assessed a variety of domains. Subjects with delusional BDD were similar to those with nondelusional BDD in terms of most variables, including most demographic features, BDD characteristics, most measures of functional impairment and quality of life, comorbidity, and family history. Delusional and nondelusional subjects also had a similar probability of remitting from BDD over 1 year of prospective follow-up. However, delusional subjects had significantly lower educational attainment, were more likely to have attempted suicide, had poorer social functioning on several measures, were more likely to have drug abuse or dependence, were less likely to currently be receiving mental health treatment, and had more severe BDD symptoms. However, when controlling for BDD symptom severity, the two groups differed only in terms of educational attainment. These findings indicate that BDD's delusional and nondelusional forms have many more similarities than differences, although on several measures delusional subjects evidenced greater morbidity, which appeared accounted for by their more severe BDD symptoms. Thus, these findings offer some support for the hypothesis that these two BDD variants may constitute the same disorder. Additional studies are needed to examine this issue, which may have relevance for other disorders with both delusional and nondelusional variants in DSM.
Assuntos
Delusões/epidemiologia , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/epidemiologia , Adolescente , Adulto , Cultura , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Transtornos Somatoformes/psicologia , Inquéritos e QuestionáriosRESUMO
PURPOSE: To carry out a randomized controlled trial of a decision aid for women at increased risk of developing ovarian cancer to facilitate decision making regarding risk management options. METHODS: This randomized trial, conducted through 6 familial cancer centers, compared the efficacy of tailored decision aid to that of a general educational pamphlet in preparing women for decision making. PARTICIPANTS: 131 women with a family history of breast and/or ovarian cancer or of hereditary nonpolyposis colorectal cancer. OUTCOME MEASURES: Decisional conflict, knowledge about ovarian cancer risk management options, and psychological adjustment were reassessed at 3 time points. RESULTS: Compared to those who received the pamphlet (control), women who received the decision aid (intervention) were significantly more likely to report a high degree of acceptability of the educational material at both follow-up assessment time points. Findings indicate neither group experienced significant increases in psychological distress at either follow-up assessment time points relative to baseline. Two weeks postintervention, the intervention group demonstrated a significant decrease in decisional conflict compared to the control group (t = 2.4, P < 0.025) and a trend for a greater increase in knowledge about risk management options (t = 2.1, P = 0.037). No significant differences were found 6 months postintervention. CONCLUSION: This form of educational material is successful in increasing knowledge about risk management options and in reducing decisional conflict in the shorter term. The decision aid is an effective and acceptable strategy for patient education to facilitate an inclusive and informed decision-making process about managing ovarian cancer risk.