Patient, Family, and Clinician Perspectives on End-of-Life Care Quality Domains and Candidate Indicators for Adolescents and Young Adults With Cancer.

Importance: End-of-life care quality indicators specific to adolescents and young adults (AYAs) aged 12 to 39 years with cancer have not been developed. Objective: To identify priority domains for end-of-life care from the perspectives of AYAs, family caregivers, and clinicians, and to propose candidate quality indicators reflecting priorities. Design, Setting, and Participants: This qualitative study was conducted from December 6, 2018, to January 5, 2021, with no additional follow-up. In-depth interviews were conducted with patients, family caregivers, and clinicians and included a content analysis of resulting transcripts. A multidisciplinary advisory group translated priorities into proposed quality indicators. Interviews were conducted at the Dana-Farber Cancer Institute, Kaiser Permanente Northern California, Kaiser Permanente Southern California, and an AYA cancer support community (lacunaloft.org). Participants included 23 AYAs, 28 caregivers, and 29 clinicians. Exposure: Stage IV or recurrent cancer. Main Outcomes and Measures: Care priorities. Results: Interviews were conducted with 23 patients (mean [SD] age, 29.3 [7.3] years; 12 men [52%]; 18 White participants [78%]), 28 family caregivers (23 women [82%]; 14 White participants [50%]), and 29 clinicians (20 women [69%]; 13 White participants [45%]). Caregivers included 22 parents (79%), 5 spouses or partners (18%), and 1 other family member (4%); the 29 clinicians included 15 physicians (52%), 6 nurses or nurse practitioners (21%), and 8 social workers or psychologists (28%). Interviews identified 7 end-of-life priority domains: attention to physical symptoms, attention to quality of life, psychosocial and spiritual care, communication and decision-making, relationships with clinicians, care and treatment, and independence. Themes were consistent across the AYA age range and participant type. Although some domains were represented in quality indicators developed for adults, unique domains were identified, as well as AYA-specific manifestations of existing domains. For example, quality of life included global quality of life; attainment of life goals, legacy, and meaning; support of personal relationships; and normalcy. Within communication and decision-making, domains included communication early in the disease course, addressing prognosis and what to expect at the end of life, and opportunity for AYAs to hold desired roles in decision-making. Care and treatment domains relevant to cancer therapy, use of life-prolonging measures, and location of death emphasized the need for preference sensitivity rather than a standard path. This finding differs from existing adult indicators that propose that late-life chemotherapy, intensive measures, and hospital death should be rare. Conclusions and Relevance: The findings of this qualitative study suggest that AYAs with cancer have priorities for care at the end of life that are not fully encompassed in existing indicators for adults. Use of new indicators for this young population may better reflect patient- and family-centered experiences of quality care.

Identification of novel common breast cancer risk variants at the 6q25 locus among Latinas.

BACKGROUND: Breast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas. METHODS: We performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach. RESULTS: We identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10- 8 - 6.0 × 10- 9) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r2 > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70-0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78-0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91-0.97; p = 0.0017). CONCLUSION: Our study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

Age of Menarche in a Longitudinal US Cohort.

STUDY OBJECTIVE: Menarche is a critical milestone in a woman's life, and historically has been determined using several approaches. The goals of this study were to: (1) determine age at menarche from multiple reports of parents and adolescent participants in a prospective study; (2) examine factors affecting age at menarche; and (3) determine correlates of menarche and pubertal tempo. DESIGN: Longitudinal observational study. SETTING: Three sites of the Breast Cancer and the Environment Research Program. PARTICIPANTS: Girls enrolled at 6-8 years of age. INTERVENTIONS AND MAIN OUTCOME MEASURES: Parental and participant reported age of menarche, and tempo of puberty. RESULTS: There were 946 girls who were assigned an age of menarche. The correlation between parent and participant reports was high (Spearman R = 0.799, P < .001), and the difference was insignificant. Median age at menarche overall was 12.25 years. Compared with black participants, Hispanic girls were more likely to have menarche earlier, whereas white and Asian girls were more likely to have menarche later. Age of menarche was highly correlated with age of breast development (Spearman R = 0.547; P < .001), and inversely with body mass index (Spearman R = -0.403; P < .001). Tempo (interval of age of breast development to menarche) was slower in those with earlier breast development. CONCLUSION: Parental and adolescent reports of menarche are highly correlated. Earlier breast maturation was associated with slower tempo through puberty. Body mass index had a greater effect on age at menarche than did race and ethnicity.

Preliminary Development and Evaluation of an Algorithm to Identify Breast Cancer Chemotherapy Toxicities Using Electronic Medical Records and Administrative Data.

PURPOSE: Breast cancer chemotherapy toxicity is not well documented outside of randomized trials. We developed and conducted preliminary evaluation of an algorithm to detect grade 3 and 4 toxicities using electronic data from a large integrated managed care organization. METHODS: The algorithm used administrative, pharmacy, and electronic data from outpatient, emergency room, and inpatient records of 99 women diagnosed with breast cancer from 2006 to 2009 who underwent chemotherapy. Data were abstracted for 12 months post-treatment initiation (24 months for trastuzumab recipients). An oncology nurse independently blindly reviewed records; these results were the "gold standard." Sensitivity and specificity were calculated for overall toxicity, categories of toxicities, and toxicity by age or regimen. The algorithm was applied to an independent sample of 1,575 patients with breast cancer diagnosed during the study period to estimate prevalence rates. RESULTS: The overall sensitivity for detecting chemotherapy-related toxicity was 89% (95% CI, 77% to 95%). The highest sensitivity was for identification of hematologic toxicities (97%; 95% CI, 84% to 99%). There were good sensitivities for infectious toxicity, but rates dropped for GI and neurological toxicities. Specificity was high within each category (89% to 99%), but when combined to measure any toxicity, it was lower (70%; 95% CI, 57% to 81%). When applied to an independent chemotherapy sample, the algorithm estimates a 26% rate of hematologic toxicity; rates were higher among patients age ≥ 65 years versus less than 65 years. CONCLUSIONS: If validated in other samples and health care settings, algorithms to capture toxicity could be useful in comparative and cost-effectiveness evaluations of community practice-delivered treatment.

Dietary flavonol intake is associated with age of puberty in a longitudinal cohort of girls.

Lignans and flavonols are dietary phytoestrogens found at high concentrations in the Western Diet. They have potential to influence the timing of puberty. We hypothesized that greater consumption of these 2 phytoestrogens would be related to later age at pubertal onset among girls. Pubertal assessment and 24-hour diet recall data were available for 1178 girls, ages 6 to 8 years (mean 7.3 years) in the Breast Cancer and Environment Research Project Puberty Study. Lignan and flavonol intakes were mainly derived from fruit and vegetable consumption. Average consumption was 6.5 mg/d for flavonols and 0.6 mg/d for lignans. Highest flavonol consumption (>5 mg/d) was associated with later breast development (adjusted hazards ratio [HR]: 0.74, 95% CI: [0.61-0.91]) compared to 2 to 5 mg/d (adjusted HR: 0.84, 95% CI: [0.70-1.0]) and <2 mg/d (referent group; P-trend = .006). Flavonol intake was not associated with pubic hair development. Lignan intake was not associated with either breast or pubic hair development. Dietary intake was only weakly correlated with urinary enterolactone, a biomarker for lignans (RS = 0.13). Consistent with biologic properties of phytoestrogens that indicate hormonal activity, their consumption may be associated with reproductive end points, even in childhood.

Adherence to the AICR cancer prevention recommendations and subsequent morbidity and mortality in the Iowa Women's Health Study cohort.

In 1997, the American Institute for Cancer Research (AICR) published 14 recommendations related to diet for individuals to reduce cancer incidence on a global basis; smoking was also discouraged. We operationalized these into nine recommendations that are particularly relevant to western populations in a cohort of 29,564 women ages 55 to 69 years at baseline in 1986 who had no history of cancer or heart disease. The cohort was followed through 1998 for cancer incidence (n = 4,379), cancer mortality (n = 1,434), cardiovascular disease (CVD) mortality (n = 1,124), and total mortality (n = 3,398). The median number (range) of recommendations followed was 4 (0-8), and 33% of the cohort had ever smoked. Women who followed no or one recommendation compared with six to nine recommendations were at an increased risk of cancer incidence [relative risk (RR) 1.35, 95% confidence interval (CI) 1.15-1.58] and cancer mortality (RR 1.43, 95% CI 1.11-1.85), but there was no association with CVD mortality (RR 1.06, 95% CI 0.78-1.43). We calculated the population attributable risk (PAR) to estimate the proportion of cancer incidence, cancer mortality, and CVD mortality that theoretically would have been avoidable if the entire cohort had never smoked, had followed six to nine recommendations, or had done both. The PARs for smoking were 11% (95% CI 10-13) for cancer incidence, 21% (95% CI 17-24) for cancer mortality, and 20% (95% CI 16-23) for CVD mortality. The PARs for not following six to nine recommendations were 22% (95% CI 12-30) for cancer incidence, 11% (95% CI -5 to 24) for cancer mortality, and 4% (95% CI -20 to 19) for CVD mortality. When smoking and the operationalized AICR recommendations were combined together, the PARs were 31% (95% CI 19-37) for cancer incidence, 30% (95% CI 15-40) for cancer mortality, and 22% (95% CI 4-36) for CVD mortality. These data suggest that the adherence to the AICR recommendations, independently and in conjunction with not smoking, is likely to have a substantial public health impact on reducing cancer incidence and, to a lesser degree, cancer mortality at the population level.

Interaction of adolescent anthropometric characteristics and family history on breast cancer risk in a Historical Cohort Study of 426 families (USA).

OBJECTIVE: To determine whether the association of adolescent anthropometric characteristics with breast cancer is modified by a family history of the disease. METHODS: These interactions were evaluated in a historical cohort of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the University of Minnesota. The occurrence of breast cancer and the measurement of risk factors in sisters, daughters, granddaughters, nieces and marry-ins was determined through telephone interviews and mailed questionnaires conducted from 1991-1996. Cox proportional hazards regression, accounting for age, birth cohort, adult body mass index (BMI), and clustering within families, was used to estimate relative risks (RR) and 95% confidence intervals (CIs) of breast cancer. RESULTS: Among 4632 women from 426 families available for analysis, there were 175 breast cancers. There was a strong interaction between degree of relationship to proband and relative weight at age 12 on breast cancer risk ( p < 0.001). Among sisters and daughters of the probands, risk of breast cancer was slightly increased in those with below average weight at age 12 (RR = 1.55; 95% CI = 0.66-3.64), and strongly increased in those with above average weight (RR = 4.25; 95% CI = 1.71-10.5), compared to those with average weight. In contrast, among marry-ins, there was a weak positive association for those with below average weight at age 12 (RR = 1.61; 95% CI = 0.91-2.83), while there was an inverse association for above average weight (RR = 0.75; 95% CI = 0.26-2.16), compared to those with average weight. There were no significant interactions between degree of relationship to proband and height ( p = 0.55), weight at age 18 ( p = 0.22) and BMI at age 18 ( p = 0.63) on breast cancer risk. CONCLUSIONS: Family history appears to modify the effect of obesity in early adolescence on subsequent breast cancer risk, and may identify differing etiologic pathways.