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Importance: Older adults with advanced cancer who have high pretreatment symptom severity often experience adverse events during cancer treatments. Unsupervised machine learning may help stratify patients into different risk groups. Objective: To evaluate whether clusters identified from baseline patient-reported symptom severity were associated with adverse outcomes. Design, Setting, and Participants: This secondary analysis of the Geriatric Assessment Intervention for Reducing Toxicity in Older Patients With Advanced Cancer (GAP70+) Trial (2014-2019) included patients who completed the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) before starting a new cancer treatment regimen and received care at community oncology sites across the United States. An unsupervised machine learning algorithm (k-means with Euclidean distance) clustered patients based on similarities of baseline symptom severities. Clustering variables included severity items of 24 PRO-CTCAE symptoms (range, 0-4; corresponding to none, mild, moderate, severe, and very severe). Total severity score was calculated as the sum of 24 items (range, 0-96). Whether the clusters were associated with unplanned hospitalization, death, and toxic effects was then examined. Analyses were conducted in January and February 2022. Exposures: Symptom severity. Main Outcomes and Measures: Unplanned hospitalization over 3 months (primary), all-cause mortality over 1 year, and any clinician-rated grade 3 to 5 toxic effect over 3 months. Results: Of 718 enrolled patients, 706 completed baseline PRO-CTCAE and were included (mean [SD] age, 77.2 [5.5] years, 401 [56.8%] male patients; 51 [7.2%] Black and 619 [87.8%] non-Hispanic White patients; 245 [34.7%] with gastrointestinal cancer; 175 [24.8%] with lung cancer; mean [SD] impaired Geriatric Assessment domains, 4.5 [1.6]). The algorithm classified 310 (43.9%), 295 (41.8%), and 101 (14.3%) into low-, medium-, and high-severity clusters (within-cluster mean [SD] severity scores: low, 6.3 [3.4]; moderate, 16.6 [4.3]; high, 29.8 [7.8]; P < .001). Controlling for sociodemographic variables, clinical factors, study group, and practice site, compared with patients in the low-severity cluster, those in the moderate-severity cluster were more likely to experience hospitalization (risk ratio, 1.36; 95% CI, 1.01-1.84; P = .046). Moderate- and high-severity clusters were associated with a higher risk of death (moderate: hazard ratio, 1.31; 95% CI, 1.01-1.69; P = .04; high: hazard ratio, 2.00; 95% CI, 1.43-2.78; P < .001), but not toxic effects. Conclusions and Relevance: In this study, unsupervised machine learning partitioned patients into distinct symptom severity clusters; patients with higher pretreatment severity were more likely to experience hospitalization and death. Trial Registration: ClinicalTrials.gov Identifier: NCT02054741.
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Neoplasias , Aprendizado de Máquina não Supervisionado , Humanos , Masculino , Estados Unidos , Idoso , Feminino , Síndrome , Neoplasias/terapia , Medidas de Resultados Relatados pelo PacienteRESUMO
PURPOSE: Providing a geriatric assessment (GA) summary with management recommendations to oncologists reduces clinician-rated toxicity in older patients with advanced cancer receiving treatment. This secondary analysis of a national cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02054741) aims to assess the effects of a GA intervention on symptomatic toxicity measured by Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS: From 2014 to 2019, the study enrolled patients age ≥ 70 years, with advanced solid tumors or lymphoma and ≥ 1 GA domain impairment, who were initiating a regimen with high prevalence of toxicity. Patients completed PRO-CTCAEs, including the severity of 24 symptoms (11 classified as core symptoms) at enrollment, 4-6 weeks, 3 months, and 6 months. Symptoms were scored as grade ≥ 2 (at least moderate) and grade ≥ 3 (severe/very severe). Symptomatic toxicity was determined by an increase in severity during treatment. A generalized estimating equation model was used to assess the effects of the GA intervention on symptomatic toxicity. RESULTS: Mean age was 77 years (range, 70-96 years), 43% were female, and 88% were White, 59% had GI or lung cancers, and 27% received prior chemotherapy. In 706 patients who provided PRO-CTCAEs at baseline, 86.1% reported at least one moderate symptom and 49.7% reported severe/very severe symptoms at regimen initiation. In 623 patients with follow-up PRO-CTCAE data, compared with usual care, fewer patients in the GA intervention arm reported grade ≥ 2 symptomatic toxicity (overall: 88.9% v 94.8%, P = .035; core symptoms: 83.4% v 91.7%, P = .001). The results for grade ≥ 3 toxicity were comparable but not significant (P > .05). CONCLUSION: In the presence of a high baseline symptom burden, a GA intervention for older patients with advanced cancer reduces patient-reported symptomatic toxicity.
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Neoplasias Pulmonares , Neoplasias , Humanos , Feminino , Idoso , Masculino , Avaliação Geriátrica , Neoplasias/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Medidas de Resultados Relatados pelo PacienteRESUMO
PURPOSE: Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens. METHODS: TrACER was a cluster randomized trial where practices were randomized to usual care or a guideline-based SOE intervention. In the primary study, sites were randomized 3:1 to SOE of automated PP-CSF orders for high FN risk regimens and alerts against PP-CSF use for low-risk regimens versus usual care. A secondary 1:1 randomization assigned 24 intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for intermediate-risk regimens. Clinicians were allowed to over-ride the SOE. Patients with breast, colorectal, or non-small-cell lung cancer were enrolled. Mixed-effect logistic regression models were used to test differences between randomized sites. RESULTS: Between January 2016 and April 2020, 846 eligible patients receiving intermediate-risk regimens were registered to either SOE to prescribe (12 sites: n = 542) or an alert to not prescribe PP-CSF (12 sites: n = 304). Rates of PP-CSF use were higher among sites randomized to SOE (37.1% v 9.9%, odds ratio, 5.91; 95% CI, 1.77 to 19.70; P = .0038). Rates of FN were low and identical between arms (3.7% v 3.7%). CONCLUSION: Although implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving first-line intermediate-risk regimens, FN rates were low and did not differ between arms. Although this guideline-informed SOE influenced prescribing, the results suggest that neither SOE nor PP-CSF provides sufficient benefit to justify their use for all patients receiving first-line intermediate-risk regimens.
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Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Neutropenia Febril , Neoplasias Pulmonares , Prescrições Permanentes , Humanos , Feminino , Fatores Estimuladores de Colônias/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/etiologia , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Neoplasias Pulmonares/tratamento farmacológico , Modelos Logísticos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/etiologiaRESUMO
Importance: Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines. Objective: To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia. Design, Setting, and Participants: This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021. Interventions: Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines. Main Outcomes and Measures: The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic. Results: A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups. Conclusions and Relevance: In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing. Trial Registration: ClinicalTrials.gov Identifier: NCT02728596.
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Fatores Estimuladores de Colônias , Sistemas de Apoio a Decisões Clínicas , Neutropenia Febril , Neoplasias , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Fatores Estimuladores de Colônias/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Neoplasias/tratamento farmacológico , IdosoRESUMO
INTRODUCTION: Caregiver-oncologist concordance regarding the patient's prognosis is associated with worse caregiver outcomes (e.g., depressive symptoms), but mechanisms underpinning these associations are unclear. We explored whether caregiving esteem mediates these associations. METHODS: At enrollment, caregivers and oncologists used a 5-point ordinal scale to estimate patient survival; identical responses were considered concordant. At 4-6 weeks, caregivers completed an assessment of the extent to which caregiving imparts self-esteem (Caregiver Reaction Assessment self-esteem subscale; range 0-5; higher score indicates greater esteem). They also completed Patient Health Questionnaire-2 (PHQ-2) for depressive symptoms, Distress Thermometer, and 12-Item Short Form Survey for quality of life (QoL). Mediation analysis with bootstrapping (PROCESS macro by Hayes) was used to estimate the extent to which caregiving mediated the effects of prognostic concordance on caregiver outcomes through caregiving esteem. RESULTS: Prognostic concordance occurred in 28% the caregiver-oncologist dyads; 85% of the discordance were due to caregivers estimating a longer patient's survival. At 4-6 weeks, mean caregiving esteem score was 4.4 (range 1.5-5.0). Lower caregiving esteem mediated the associations of concordance with higher PHQ-2 [indirect effect = 0.12; 95% Confidence Interval (CI) 0.03, 0.27], greater distress (indirect effect =0.25; 95% CI 0.08, 0.48), and poorer QoL (indirect effect = -1.50; 95% CI -3.06, -0.41). Caregiving esteem partially mediated 39%, 64%, and 48% of the associations between caregiver-oncologist concordance and PHQ-2, distress, and SF-12, respectively. CONCLUSIONS: Caregiver-oncologist concordance was associated with lower caregiving esteem. Lower caregiving esteem mediated the negative relationship between caregiver-oncologist concordance and caregiver outcomes.
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Cuidadores , Oncologistas , Humanos , Prognóstico , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient-caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty. METHODS: This secondary analysis used longitudinal data from a national cluster-randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9-item Mishel Uncertainty in Illness Scale at enrollment, 4-6 weeks, 3 months, and 6 months. The dyadic growth model and cross-lagged actor-partner interdependence model were used. RESULTS: A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = -0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = -0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time. CONCLUSIONS: Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.
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Cuidadores , Neoplasias , Idoso , Cuidadores/psicologia , Avaliação Geriátrica , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Qualidade de Vida/psicologia , IncertezaRESUMO
OBJECTIVES: Oncologists estimate patients' prognosis to guide care. Evidence suggests oncologists tend to overestimate life expectancy, which can lead to care with questionable benefits. Information obtained from geriatric assessment may improve prognostication for older adults. In this study, we created a geriatric assessment-based prognostic model for older adults with advanced cancer and compared its performance to alternative models. MATERIALS AND METHODS: We conducted a secondary analysis of a trial (URCC 13070; PI: Mohile) capturing geriatric assessment and vital status up to one year for adults age ≥ 70 years with advanced cancer. Oncologists estimated life expectancy as 0-6 months, 7-12 months, and > 1 year. Three statistical models were developed: (1) a model including age, sex, cancer type, and stage (basic model), (2) basic model + Karnofsky Performance Status (≤50, 60-70, and 80+) (KPS model), and (3) basic model +16 binary indicators of geriatric assessment impairments (GA model). Cox regression was used to model one-year survival; c-indices and time-dependent c-statistics assessed model discrimination and stratified survival curves assessed model calibration. RESULTS: We included 484 participants; mean age was 75; 48% had gastrointestinal or lung cancer. Overall, 43% of patients died within one year. Oncologists classified prognosis accurately for 55% of patients, overestimated for 35%, and underestimated for 10%. C-indices were 0.61 (basic model), 0.62 (KPS model), and 0.63 (GA model). The GA model was well-calibrated. CONCLUSIONS: The GA model showed moderate discrimination for survival, similar to alternative models, but calibration was improved. Further research is needed to optimize geriatric assessment-based prognostic models for use in older adults with advanced cancer.
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Avaliação Geriátrica , Neoplasias , Idoso , Humanos , Avaliação de Estado de Karnofsky , Expectativa de Vida , Neoplasias/terapia , PrognósticoRESUMO
OBJECTIVES: Physician assistants (PAs) and NPs are essential to quality care delivery. The need to demonstrate value and optimize PA and NP roles in neurology subspecialty clinics is unmet. We outline the development of a PA- and NP-led neuro-oncology procedural clinic and provide metrics to support the institutional and clinician value added. METHODS: We designed a PA- and NP-led Geisinger Ommaya Clinic (GOC) to manage leptomeningeal carcinomatosis (LMC) with defined clinician roles and the GOC treatment protocol. A retrospective review of 135 patients (2012-2019) compared survival outcomes for patients treated on the protocol compared with those treated off the protocol. RESULTS: Centralized care in the GOCs minimized shared physician encounters and improved PA and NP autonomy and utility. LMC therapy as part of the GOC protocol improved care continuity and survival outcomes. CONCLUSIONS: PA- and NP-led procedural clinics optimize use of these clinicians and open physician availability for nonprocedural duties. This research highlights the institutional patient and financial benefit while demonstrating the operational and leadership growth potential for PAs and NPs.
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Carcinomatose Meníngea , Profissionais de Enfermagem , Assistentes Médicos , Atenção à Saúde , Humanos , Carcinomatose Meníngea/tratamento farmacológico , Estudos RetrospectivosRESUMO
Despite strong evidence that it is efficacious, chemoprevention has been underused in eligible women. Reasons offered not to adopt and initiate strategies to reduce the risk of breast cancer include the fear of adverse effects, medication costs, lack of reasonably accurate and feasible methods for assessing an individual's personal risk, and lack of established risk thresholds that maximize benefit and minimize harms. The article by Macdonald and colleagues remind us that the problem of lack of uptake of risk-reducing medications for breast cancer remains a worldwide clinical challenge despite endorsements from national and international organizations that recommend the use of risk-reducing medications for breast cancer with level I evidence. Several strategies are suggested to improve uptake and utilization of safe and effective chemoprevention medications with high therapeutic indices.See related article by Macdonald et al., p. 131.
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Neoplasias da Mama , Neoplasias da Mama/prevenção & controle , Quimioprevenção , Feminino , HumanosRESUMO
OBJECTIVES: Older self-perceived age is associated with poor health and higher healthcare utilization in the geriatric population. We evaluated the associations of self-perceived age with geriatric assessment (GA) domain impairments in older adults with cancer. METHODS: This was a secondary analysis of baseline data from a GA cluster-randomized trial (URCC 13070; PI: Mohile). We included patients aged ≥70 with incurable stage III/IV solid tumor or lymphoma considering or receiving treatment and had ≥1 GA domain impairment other than polypharmacy. Multivariate analyses were used to evaluate the associations of age difference between chronological and self-perceived age (categorized into "feeling younger than chronological age" vs. "feeling the same or older than their chronological age") with GA domain impairments. RESULTS: We included 533 patients; mean age was 76.6 (SD 5.2). On multivariate analyses, compared to those who felt younger than their chronological age, those who felt the same or older were more likely to have impairments in physical performance [Adjusted Odds Ratio (AOR) 5.42, 95% Confidence Interval (CI) 1.69-17.40)], functional status (AOR 2.31, 95% CI 1.73-3.07), comorbidity (AOR 1.62, 95% CI 1.20-2.19), psychological health (AOR 2.62, 95% CI 1.85-3.73), and nutrition (AOR 1.65, 95% CI 1.20-2.28). They were also more likely to screen positively for polypharmacy (AOR 1.86, 95% CI 1.30-2.65). CONCLUSIONS: Older adults with cancer who felt the same or older than their chronological age were more likely to have GA domain impairments. Further studies are needed to better understand the relationships between self-perceived age, aging-related conditions, and outcomes in this population.
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Avaliação Geriátrica , Neoplasias , Autoimagem , Fatores Etários , Idoso , Comorbidade , Humanos , Saúde Mental , PolimedicaçãoRESUMO
Millions of women in the United States are at increased risk of breast cancer. Multiple prospective, randomized clinical trials have demonstrated both the efficacy and safety of selective estrogen receptor modulators and aromatase inhibitors in reducing substantially the risk of invasive breast cancer in women at increased risk. Published tables are available to aid clinicians in shared decision-making regarding drug interventions with their patients who are at increased risk of breast cancer. Both professional and governmental agencies have advised that these interventions should be offered to women at increased risk of breast cancer. Doing so would reduce breast cancer morbidity substantially.
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Neoplasias da Mama/prevenção & controle , Inibidores da Aromatase/uso terapêutico , Feminino , Humanos , Comportamento de Redução do Risco , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Estados UnidosRESUMO
Importance: Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives: To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants: This is a cross-sectional study of adult volunteers (n = 50â¯726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Main Outcomes: Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Results: Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing. Conclusions and Relevance: This study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.
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Proteína BRCA1/análise , Proteína BRCA2/análise , Sequenciamento do Exoma/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Bancos de Espécimes Biológicos/estatística & dados numéricos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Estudos Transversais , Detecção Precoce de Câncer/métodos , Exoma/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania , Virulência/genética , Sequenciamento do Exoma/estatística & dados numéricosRESUMO
PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.
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Bancos de Espécimes Biológicos , Detecção Precoce de Câncer/métodos , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Pessoa de Meia-Idade , Linhagem , Sequenciamento Completo do GenomaRESUMO
Despite FDA approval of drugs to reduce the risk of breast cancer in women at increased risk, uptake of these drugs has been poor despite the publication of numerous studies that demonstrate both their effectives and safety. National organizations have made recommendations for their use, but both physicians and their patients do not fully understand either breast cancer risk factors or risk assessment or the indications for using risk-reducing agents. Histologically predisposing conditions, such as ductal or lobular atypia and lobular carcinoma in situ, impart particularly high risks of developing subsequent invasive breast cancer. Resources should be committed to both provider and patient education to reduce the risk of breast cancer in women who are at increased risk. Cancer Prev Res; 10(8); 431-3. ©2017 AACR.
RESUMO
Selective estrogen receptor modulators (SERMs) reduce the risk of recurrence of invasive breast cancer and the incidence of first breast cancers in women who are at increased risk. Multiple, randomized clinical trials have shown both the efficacy and safety of SERMs in reducing the risk of breast cancer. Long-term follow-up as long as 20 years in the randomized trials shows persistent efficacy with acceptable safety. Hormone replacement therapy given concurrently with tamoxifen abrogates its preventive effect, but women with atypical hyperplasia derive particular benefit from SERM therapy. Aromatase inhibitors also reduce the risk of developing invasive breast cancer, but the experience with them for risk reduction is limited to few trials. National organizations have made recommendations to use SERMs and aromatase inhibitors to reduce the risk of breast cancer in high-risk women and additional efforts should be made to increase their use in clinical practice, where the number of women needed to treat to prevent one case of breast cancer conforms to accepted standards of preventive medicine.
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Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Tamoxifeno/uso terapêuticoRESUMO
Risk for breast cancer can be easily and rapidly assessed using validated, quantitative models. Multiple randomized studies show that the selective estrogen response modifiers (SERMs) tamoxifen and raloxifene can safely reduce the risk of invasive breast cancer in both pre- and postmenopausal women. Treatment resulted in a 38% reduction in breast cancer incidence, and 42 women would need to be treated to prevent one breast cancer event in the first 10 years of follow-up. Reduction was larger in the first 5 years of follow-up than in years 5 to 10, but no studies treated patients for longer than 5 years. Thromboembolic events were significantly increased with all SERMs, whereas vertebral fractures were reduced. Tamoxifen provides net benefit to all premenopausal women who are at increased risk, whereas raloxifene reduces risk nearly as much in postmenopausal women and offers increased safety. Both tamoxifen and raloxifene reduce the incidence of in situ cancers. Lasofoxifene reduced the risk of breast cancer by 79% in postmenopausal women with osteoporosis. The MAP3 trial showed a 65% reduction in the annual incidence of invasive breast cancer in postmenopausal women who were at moderately increased risk for breast cancer who took the aromatase inhibitor exemestane. The IBIS-II trial showed a 53% reduction in the risk of invasive breast cancer in postmenopausal women aged 40 to 70 who took the aromatase inhibitor anastrozole. Of the 50 million white women in the United States aged 35 to 79, 2.4 million would have a positive benefit/risk index for chemoprevention.
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Anticarcinógenos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Neoplasias Hormônio-Dependentes/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Adulto , Fatores Etários , Idoso , Anticarcinógenos/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Medicina Baseada em Evidências , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/epidemiologia , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Fatores de Proteção , Medição de Risco , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS: A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committee's review of the literature. RESULTS: Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole. RECOMMENDATIONS: In women at increased risk of BC age ≥ 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) -positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC ≥ 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent.