Hereditary breast and ovarian cancer due to mutations in the BRCA1 and BRCA2 genes is the most common cause of hereditary forms of both breast and ovarian cancer. The overall prevalence of BRCA1/2 ...mutations is estimated to be from 1 in 400 to 1 in 800 with a higher prevalence in the Ashkenazi Jewish population (1 in 40). Estimates of penetrance (cancer risk) vary considerably depending on the context in which they were derived and have been shown to vary within families with the same BRCA1/2 mutation. This suggests there is no exact risk estimate that can be applied to all individuals with a BRCA1/2 mutation. The likelihood of harboring a BRCA1 or BRCA2 mutation is dependent on one's personal and/or family history of cancer and can be estimated using various mutation probability models. For those individuals who have a BRCA1 or BRCA2 mutation, several screening and primary prevention options have been suggested, including prophylactic surgery and chemoprevention. Once a BRCA1 or BRCA2 mutation has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial mutation and thus need increased surveillance and early intervention when a cancer is diagnosed.
IMPORTANCE: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. OBJECTIVES: To estimate age-specific risks of breast, ovarian, and ...contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. EXPOSURES: BRCA1/2 mutations, family cancer history, and mutation location. MAIN OUTCOMES AND MEASURES: Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. RESULTS: Among 3886 women (median age, 38 years; interquartile range IQR, 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio HR for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). CONCLUSIONS AND RELEVANCE: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
Purpose
Cancer survivors’ needs around sexual concerns are often unmet. The primary objective of this systematic review was to examine the prevalence of and factors associated with patient-provider ...communication about sexual concerns in cancer.
Methods
Using PRISMA guidelines, we searched PubMed/MEDLINE, PsychInfo, and CINAHL databases for peer-reviewed quantitative research papers (2000–2015) in cancer samples. Search terms across three linked categories were used (sexuality, communication, and cancer). The National Comprehensive Cancer Network (NCCN) Sexual Function Guidelines were used as a framework to categorize communication reported in each study.
Results
Twenty-nine studies from 10 countries (29 % in USA) were included. Studies assessed patients only (21), providers only (4), and both (4). Communication measures differed across studies and many lacked validity data. When reported by patients or providers, the average prevalence of discussing potential treatment effects on sexual function was 50 (60 % for men and 28 % for women) and 88 %, respectively. As reported by patients or providers, respectively, assessing patients’ sexual concerns (10 and 21 %) and offering treatments (22 and 17 %) were measured in fewer studies and were reported less frequently. Both patients and providers (28 and 32 %, respectively) reported a low prevalence of other non-specific communication. Greater prevalence of communication was associated with male patient gender and more years of provider experience.
Conclusions
Sexual issues go unaddressed for many cancer survivors, particularly women. Both patient and provider interventions are needed.
Implications for Cancer Survivors
Enhancing patient-provider communication about sexual concerns through evidence-based interventions could improve patient sexual function and quality of life.
The Risk Assessment Program (RAP) at Fox Chase Cancer Center (Philadelphia, PA) is a multi-generational prospective cohort, enhanced for personal and family history of cancer, consisting of over ...10,000 individuals for whom data on personal and family history of cancer, risk factors, genetic and genomic data, health behaviors, and biospecimens are available. The RAP has a broad research agenda including the characterization of genes with known or potential relevance to cancer, gene-gene and gene-environment interactions, and their contribution to clinically useful risk assessment and risk reduction strategies. Increasingly, this body of research is identifying genetic changes which may have clinical significance for RAP research participants, leading us to confront the issue of whether to return genetic results emerging from research laboratories. This review will describe some of the important fundamental points that must be debated as we develop a paradigm for return of research results. The key issues to address as the scientific community moves toward adopting a policy of return of research results include the best criteria for determining which results to offer, the consent document components necessary to ensure that the participant makes a truly informed decision about receiving their results, and associated logistical and cost challenges.
.
Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that ...incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.
A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).
Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included
and mismatch repair genes, with broader testing, such as
, for clinical trial eligibility.
was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for
carriers, with consideration in
, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.
This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
Genetic testing for cancer susceptibility genes is increasingly being integrated into medical care. Test results help inform risks of the individual being tested as well as family members who could ...benefit from knowing the results. The responsibility for informing relatives of genetic test results falls on the proband, the first family member being tested. However, there are several challenges associated with sharing genetic test results within families including incomplete understanding of test results, emotional distance among family members, and poor communication skills. In this paper we describe the communication process between probands randomized to receive
BRCA1/2
genetic test results in an enhanced versus a standard of care counseling session, and their first degree relatives with whom they shared results. We contacted 561 first degree relatives of probands who had undergone
BRCA1/2
genetic testing to measure their level of understanding of the test results, their difficulty and distress upon hearing the results, the impact of the test results on their risk perception, and their intention to pursue genetic counseling/testing. 82.1 % of relatives correctly reported the test results of their proband. Distress upon hearing the test result was highest for those relatives whose proband received informative test results. Relatives reported a decrease in cancer risk perception after hearing the test results, regardless of the type of result. Intention to pursue counseling/testing was low, even among those relatives whose proband received informative test results. Male relatives were less likely to be informed of test results and more likely to forget hearing them. These results suggest ways to improve the communication process within families.
Despite increasing calls to integrate sexual health into routine cancer care, the majority of women diagnosed with cancer do not receive information regarding how their cancer treatments will affect ...their sexual health. With the significant challenges that exist to clinical discussion of sexual health, efforts on multiple fronts are needed to close the gap in the care of women diagnosed with cancer.
The association between body mass index (BMI) and risk of breast cancer depends on time of life, but it is unknown whether this association depends on a woman's familial risk.
We conducted a ...prospective study of a cohort enriched for familial risk consisting of 16,035 women from 6701 families in the Breast Cancer Family Registry and the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer followed for up to 20 years (mean 10.5 years). There were 896 incident breast cancers (mean age at diagnosis 55.7 years). We used Cox regression to model BMI risk associations as a function of menopausal status, age, and underlying familial risk based on pedigree data using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), all measured at baseline.
The strength and direction of the BMI risk association depended on baseline menopausal status (P < 0.001); after adjusting for menopausal status, the association did not depend on age at baseline (P = 0.6). In terms of absolute risk, the negative association with BMI for premenopausal women has a much smaller influence than the positive association with BMI for postmenopausal women. Women at higher familial risk have a much larger difference in absolute risk depending on their BMI than women at lower familial risk.
The greater a woman's familial risk, the greater the influence of BMI on her absolute postmenopausal breast cancer risk. Given that age-adjusted BMI is correlated across adulthood, maintaining a healthy weight throughout adult life is particularly important for women with a family history of breast cancer.
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