Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk.

OBJECTIVE: To evaluate the risks, benefits, and utility of testing for adult-onset hereditary breast and ovarian cancer (HBOC) in adolescents and young adults. STUDY DESIGN: We evaluated interest in genetic testing of adolescents for adult-onset HBOC genes through semistructured interviews with mothers and adolescents who had previously participated in breast cancer research or had pursued (mothers) clinical testing for HBOC. RESULTS: The majority of mothers (73%) and daughters (75%) were interested in the daughter having genetic testing and were motivated by the future medical utility and current social utility of relieving anxiety and allowing them to prepare. Mothers and daughters both reported that approximately 3 years in the future was the best time to test the daughter regardless of the current age of the daughter. Overall, both mothers and daughters expressed the importance of the involvement of the mother to provide educational and emotional support but ultimately it was the daughter's decision to test. Balancing the independence and maturity of the daughter while reinforcing communication and support within the dyad was a prominent theme throughout the interviews. CONCLUSIONS: There is interest among some high-risk adolescents and young adults to engage in genetic counseling and undergo testing. Providing pretest and posttest genetic counseling, assessing preferences for parent involvement, and offering psychosocial support may be important if genetic testing for HBOC is offered to adolescents and young adults before age 25 years.

Mothers' Diet and Family Income Predict Daughters' Healthy Eating.

INTRODUCTION: Understanding the degree to which parents may influence healthy behaviors may provide opportunities to intervene among populations at increased risk of diseases, such as breast cancer. In this study, we examined the association between daughters' healthy eating habits and family lifestyle behaviors among girls and their families by using baseline data from the LEGACY (Lessons in Epidemiology and Genetics of Adult Cancer from Youth) Girls Study. Our objective was to examine the relationship between daughters' healthy eating and family lifestyle behaviors and to compare these associations between families with and without a history of breast cancer. METHODS: We examined demographic and lifestyle data from a cohort of 1,040 girls aged 6 to 13 years from year 1 (2011) of the LEGACY study. Half had a family history of breast cancer (BCFH). We used mixed-effects linear regression to assess the influence of the mother and father's physical activity, family relationship scores, the mother's diet, the family's income, and the daughter's sports participation, age, body mass index (BMI), and race/ethnicity on the daughter's Healthy Eating Index (HEI) score. RESULTS: Daughters' healthy eating was significantly correlated with the mother's diet (r[668] = 0.25, P = .003) and physical activity (r[970] = 0.12, P = .002), the father's physical activity (r[970] = 0.08, P = .01), and the family income (r[854] = 0.13, P = .006). Additionally, the mother's diet (ß coefficient = 0.71, 95% CI, 0.46-0.88, P = .005) and family income (ß coefficient = 3.28, 95% CI, 0.79-5.78, P = .002) significantly predicted a daughter's healthy eating. Analyses separated by family history status revealed differences in these associations. In families without a history of breast cancer, only the mother's diet (ß coefficient = 0.62; 95% CI, 0.29-0.95; P = .001) significantly predicted the daughter's healthy eating. In families with a history of breast cancer, the mother's diet (ß coefficient = 0.73, 95% CI, 0.42-1.03, P = .006) and family income (ß coefficient = 6.24; 95% CI, 2.68-9.80; P = .004) significantly predicted a daughter's healthy eating. CONCLUSION: A mother's diet and family income are related to the daughter's healthy eating habits, although differences exist among families by family history of breast cancer.

Comparison of methods to assess onset of breast development in the LEGACY Girls Study: methodological considerations for studies of breast cancer.

BACKGROUND: Younger age at onset of breast development, which has been declining in recent decades, is associated with increased breast cancer risk independent of age at menarche. Given the need to study the drivers of these trends, it is essential to validate methods to assess breast onset that can be used in large-scale studies when direct clinical assessment of breast onset is not feasible. METHODS: Breast development is usually measured by Tanner stages (TSs), assessed either by physical examination or by mother's report using a picture-based Sexual Maturation Scale (SMS). As an alternative, a mother-reported Pubertal Development Scale (PDS) without pictures has been used in some studies. We compared agreement of SMS and PDS with each other (n = 1022) and the accuracy of PDS with clinical TS as a gold standard for the subset of girls with this measure (n = 282) using the LEGACY cohort. We further compared prediction of breast onset using ROC curves and tested whether adding urinary estrone 1-glucuronide (E1G) improved the AUC. RESULTS: The agreement of PDS with SMS was high (kappa = 0.80). The sensitivity of PDS vs clinical TS was 86.6%. The AUCs for PDS alone and SMS alone were 0.88 and 0.79, respectively. Including E1G concentrations improved the AUC for both methods (0.91 and 0.86 for PDS and SMS, respectively). CONCLUSIONS: The PDS without pictures is a highly accurate, sensitive, and specific method for assessing breast onset, especially in settings where clinical TS is not feasible. In addition, it is comparable to SMS methods with pictures and thus easier to implement in large-scale studies, particularly phone-based interviews where pictures may not be available. Urinary E1G can improve accuracy over than PDS or SMS alone.

Body mass index rebound and pubertal timing in girls with and without a family history of breast cancer: the LEGACY girls study.

BACKGROUND: Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty. METHODS: In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models. RESULTS: The median age at BMI rebound was 5.3 years (interquartile range: 3.6-6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83-0.97) and menarche (HR = 0.86; 95% CI = 0.79-0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development. CONCLUSIONS: Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk.

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

Comparison of Clinical, Maternal, and Self Pubertal Assessments: Implications for Health Studies.

BACKGROUND: Most epidemiologic studies of puberty have only 1 source of pubertal development information (maternal, self or clinical). Interpretation of results across studies requires data on reliability and validity across sources. METHODS: The LEGACY Girls Study, a 5-site prospective study of girls aged 6 to 13 years (n = 1040) collected information on breast and pubic hair development from mothers (for all daughters) and daughters (if ≥10 years) according to Tanner stage (T1-5) drawings. At 2 LEGACY sites, girls (n = 282) were also examined in the clinic by trained professionals. We assessed agreement (κ) and validity (sensitivity and specificity) with the clinical assessment (gold standard) for both the mothers' and daughters' assessment in the subcohort of 282. In the entire cohort, we examined the agreement between mothers and daughters. RESULTS: Compared with clinical assessment, sensitivity of maternal assessment for breast development was 77.2 and specificity was 94.3. In girls aged ≥11 years, self-assessment had higher sensitivity and specificity than maternal report. Specificity for both mothers and self, but not sensitivity, was significantly lower for overweight girls. In the overall cohort, maternal and daughter agreement for breast development and pubic hair development (T2+ vs T1) were similar (0.66, [95% confidence interval 0.58-0.75] and 0.69 [95% confidence interval 0.61-0.77], respectively), but declined with age. Mothers were more likely to report a lower Tanner stage for both breast and pubic hair compared with self-assessments. CONCLUSIONS: These differences in validity should be considered in studies measuring pubertal changes longitudinally when they do not have access to clinical assessments.