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Systemic Treatment Strategies for Patients with Hereditary Breast Cancer Syndromes.

ABSTRACT: Hereditary breast cancer syndromes are associated with an increased risk of breast cancer and constitute a unique patient population, making up approximately 5%-10% of breast cancer cases in the United States. By virtue of the germline mutations that define these syndromes, invasive breast cancers in these patients have unique mechanisms that can be rationally targeted for therapeutic opportunities distinct from standard of care treatments in nongermline mutation associated breast cancers. This review intends to describe existing data on several of the most common hereditary breast cancer syndromes, including BRCA-related breast cancer syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer syndrome, specifically focusing on rational therapeutics utilized in these distinct patient subgroups and completed or ongoing clinical trials evaluating their efficacy. By exploiting the distinct biologic features associated with these syndromes, tailored treatment strategies have the potential for improved efficacy and lower toxicity. Knowledge of the emergence of these targeted cancer therapies is critical for appropriate management in these patients, extending beyond treatment to highlight the need for appropriate genetic screening to allow for early recognition of these patients and therefore appropriate treatment.Molecular testing allows for identification of germline mutations that place individuals at high risk for breast cancer and that are associated with distinct histopathology and molecular characteristics that define the invasive breast cancer cases that these patients develop. These unique characteristics may ultimately provide rational targets for systemic treatments with improvements in both morbidity and efficacy. Identification of patients with these germline mutations is important for not only appropriate screening and prophylaxis, but knowledge of therapies specifically targeting several of the most common hereditary breast cancer syndromes is essential to ensure appropriate treatment of invasive breast cancers in these patients.

SUBMITTER: Parkes A

PROVIDER: S-EPMC5469585 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Systemic Treatment Strategies for Patients with Hereditary Breast Cancer Syndromes.

Parkes Amanda A Arun Banu K BK Litton Jennifer K JK

The oncologist 20170503 6

Hereditary breast cancer syndromes are associated with an increased risk of breast cancer and constitute a unique patient population, making up approximately 5%-10% of breast cancer cases in the United States. By virtue of the germline mutations that define these syndromes, invasive breast cancers in these patients have unique mechanisms that can be rationally targeted for therapeutic opportunities distinct from standard of care treatments in nongermline mutation associated breast cancers. This ...[more]

PMID: 28469042

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Project description:Hereditary cancer syndromes constitute approximately 10% of all cancers. Cascade testing involves testing of at-risk relatives to determine if they carry the familial pathogenic variant. Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. We searched major databases using keywords and subject heading of "cascade testing". Interventions proposed in each study were classified according to the Effective Practice and Organization of Care (EPOC) taxonomy. Quality of intervention description was assessed using the TIDieR checklist, and evaluation of implementation outcomes was performed using Proctor's Implementation Outcomes Framework. Improvements in rates of genetic testing uptake was seen in interventions across the different EPOC taxonomy strategies. The average TIDieR score was 7.3 out of 12. Items least reported include modifications (18.5%), plans to assess fidelity/adherence (7.4%) and actual assessment of fidelity/adherence (7.4%). An average of 2.9 out of 8 aspects of implementation outcomes were examined. The most poorly reported outcomes were cost, fidelity and sustainability, with only 3.7% of studies reporting them. Most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream. Therefore, further adoption of standardized guidelines in reporting of interventions and formal assessment of implementation outcomes may help promote translation of these interventions into routine practice.

Project description:BackgroundBreast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management.ObjectiveCascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives.MethodsCASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages.ResultsDescriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes.ConclusionsRobust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions.Trial registrationClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt).

Dataset Information

Systemic Treatment Strategies for Patients with Hereditary Breast Cancer Syndromes.

Publications

Systemic Treatment Strategies for Patients with Hereditary Breast Cancer Syndromes.

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