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Background: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. Methods: With the use of a multistate, registry‐linkage cohort study, BDNCO–embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. Results: The risk of embryonal tumors among those with BDNCOs was 0.09% (co‐occurring n = 105) compared to 0.03% (95% CI, 0.03%–0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5–5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3–22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3–4.2) and nephroblastoma (2.9; 95% CI, 1.9–4.4) were elevated. There was no notable HRM by the aforementioned factors. Conclusions: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions. Associations between nonchromosomal birth defects of neural crest cell developmental origins and pediatric embryonal tumors were investigated based on potential shared developmental pathways. With the use of data from a multistate, registry‐linkage cohort study, children born with these birth defects were found to be more likely (hazard ratio, 4.2; 95% CI, 3.5–5.1) to be diagnosed with the selected embryonal tumors than children without a birth defect, especially hepatoblastoma (hazard ratio, 16.1; 95% CI, 11.3–22.9). [ABSTRACT FROM AUTHOR]

Background: Fertility preservation (FP) may be underused after cancer diagnosis because of uncertainty around delays to cancer treatment and subsequent reproductive success. Methods: Women aged 15 to 39 years diagnosed with cancer between 2004 and 2015 were identified from the North Carolina Central Cancer Registry. Use of assisted reproductive technology (ART) after cancer diagnosis between 2004 and 2018 (including FP) was assessed through linkage to the Society for Assisted Reproductive Technology. Linear regression was used to examine time to cancer treatment among women who did (n = 95) or did not (n = 469) use FP. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% CIs for pregnancy and birth based on timing of ART initiation relative to cancer treatment (n = 18 initiated before treatment for FP vs n = 26 initiated after treatment without FP). Results: The median time to cancer treatment was 9 to 33 days longer among women who used FP compared with women who did not, matched on clinical factors. Women who initiated ART before cancer treatment may be more likely to have a live birth given pregnancy compared with women who initiated ART after cancer treatment (age‐adjusted RR, 1.47; 95% CI, 0.98‐2.23), though this may be affected by the more frequent use of gestational carriers in the former group (47% vs 20% of transfer cycles, respectively). Conclusions: FP delayed gonadotoxic cancer treatment by up to 4.5 weeks, a delay that would not be expected to alter prognosis for many women. Further study of the use of gestational carriers in cancer populations is warranted to better understand its effect on reproductive outcomes. In this statewide retrospective cohort, adolescent and young adult women with cancer who used fertility preservation experienced up to a 4.5‐week delay in receipt of first gonadotoxic cancer treatment, but may have an increased likelihood of live birth after achieving pregnancy compared to women with cancer who used assisted reproduction without prior fertility preservation. [ABSTRACT FROM AUTHOR]

Background: Young adult cancer survivors experience frailty and decreased muscle mass at rates equivalent to much older noncancer populations, which indicate accelerated aging. Although frailty and low muscle mass can be identified in survivors, their implications for health‐related quality of life are not well understood. Methods: Through a cross‐sectional analysis of young adult cancer survivors, frailty was assessed with the Fried frailty phenotype and skeletal muscle mass in relation to functional and quality of life outcomes measured by the Medical Outcomes Survey Short‐Form 36 (SF‐36). z tests compared survivors with US population means, and multivariable linear regression models estimated mean SF‐36 scores by frailty and muscle mass with adjustments made for comorbidities, sex, and time from treatment. Results: Sixty survivors (median age, 21 years; range, 18‐29) participated in the study. Twenty‐five (42%) had low muscle mass, and 25 were either frail or prefrail. Compared with US population means, survivors reported worse health and functional impairments across SF‐36 domains that were more common among survivors with (pre)frailty or low muscle mass. In multivariable linear modeling, (pre)frail survivors (vs nonfrail) exhibited lower mean scores for general health (−9.1; P =.05), physical function (−14.9; P <.01), and overall physical health (−5.6; P =.02) independent of comorbid conditions. Conclusions: Measures of frailty and skeletal muscle mass identify subgroups of young adult cancer survivors with significantly impaired health, functional status, and quality of life independent of medical comorbidities. Identifying survivors with frailty or low muscle mass may provide opportunities for interventions to prevent functional and health declines or to reverse this process. Lay Summary: Young adult cancer survivors age more quickly than peers without cancer, which is evidenced by a syndrome of decreased resilience known as frailty.The relationship between frailty (and one of its common components, decreased muscle mass) and quality of life among young adult cancer survivors was examined.Measuring decreased muscle mass and frailty identifies young survivors with poor quality of life, including worse general health, fatigue, physical function, and overall physical health, compared with nonfrail survivors.Interventions to address components of frailty (low muscle mass and weakness) may improve function and quality of life among young adult cancer survivors. Measuring decreased muscle mass and frailty identifies young adult cancer survivors with poor quality of life, including worse general health, fatigue, physical function, and overall physical health, compared with nonfrail survivors. Interventions to address components of frailty (low muscle mass and weakness) may improve function and quality of life among young adult cancer survivors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Improvements in cancer survival mean that an increasing number of survivors may live long enough beyond their initial cancer to be diagnosed with additional independent primary cancers. The proportion of newly diagnosed cancers that are second‐ or higher‐order primaries and how this proportion has changed over the past several decades were examined. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify incident malignant primaries diagnosed between 1975 and 2017. Using the SEER sequence number, the authors tabulated the proportion of all cancers in each calendar year that were second‐ or higher‐order primaries. The average annual percent change (AAPC) was then calculated to assess how this proportion has changed over time. RESULTS: Analyses included nearly 4.9 million incident cancers diagnosed during 1975‐2017. The proportion of all cancers that were second‐ or higher‐order increased steadily from 9.77% during 1975‐1984 to 21.03% during 2015‐2017, reflecting an AAPC of 2.41% (95% CI, 2.16%‐2.65%). In 2015‐2017, second‐ or higher‐order cancers were most prevalent among cancers of the bladder (28.79%), followed by lung and bronchus (28.07%), melanoma (27.88%), and leukemia (26.10%). The highest AAPCs over the study period were observed for melanoma (4.05%), leukemia (3.51%), and lung and bronchus (3.36%). CONCLUSIONS: The proportion of newly diagnosed cancers that are second‐ or higher‐order has grown rapidly over the past several decades and currently exceeds 20%. Continued monitoring of second and later primaries will be critical for anticipating the future impact on cancer treatment and survivorship care. In the United States, the proportion of newly diagnosed cancers that are second‐ or higher‐order has grown rapidly over the past several decades and currently exceeds 20%. Because the challenges associated with 2 or more primary cancer diagnoses may be substantial and unique, continued monitoring of second‐ or higher‐order cancers will be critical for anticipating the future impact on cancer treatment and survivorship care. [ABSTRACT FROM AUTHOR]

Background: Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health‐related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated. Methods: The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient‐Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all‐cause mortality. Results: HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow‐up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05‐1.11; HR for mental T scores, 1.03; 95% CI, 1.01‐1.06). Conclusions: Prognostic and cancer treatment–related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well‐being and mortality risk. Lay Summary: Findings from a study suggest that prognostic and cancer treatment–related factors affect health‐related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk.The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care. Data from a nationwide sample of US breast cancer survivors are used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health‐related quality of life (HRQOL). The findings suggest that prognostic and cancer treatment–related factors affect HRQOL in breast cancer survivors and that poor HRQOL may increase mortality risk. [ABSTRACT FROM AUTHOR]

Background: The importance of addressing adverse financial effects of cancer among adolescents and young adults (AYAs) is paramount as survival improves. In the current study, the authors examined whether cancer‐related employment disruption was associated with financial hardship among female AYA cancer survivors in North Carolina and California. Methods: AYA cancer survivors identified through the North Carolina Central Cancer Registry and the Kaiser Permanente Northern/Southern California tumor registries responded to an online survey. Disrupted employment was defined as reducing hours, taking temporary leave, or stopping work completely because of cancer. Financial hardship was defined as material conditions or psychological distress related to cancer. Descriptive statistics and chi‐square tests were used to characterize the invited sample and survey respondents. Marginal structural binomial regression models were used to estimate prevalence differences (PDs) and 95% confidence intervals (95% CIs). Results: Among 1328 women employed at the time of their diagnosis, women were a median age of 34 years at the time of diagnosis and 7 years from diagnosis at the time of the survey and approximately 32% experienced employment disruption. A substantial percentage reported financial hardship related to material conditions (27%) or psychological distress (50%). In adjusted analyses, women with disrupted employment had a 17% higher burden of material conditions (95% CI, 10%‐23%) and an 8% higher burden of psychological distress (95% CI, 1%‐16%) compared with those without disruption. Conclusions: Financial hardship related to employment disruption among female AYA cancer survivors can be substantial. Interventions to promote job maintenance and transition back to the workforce after treatment, as well as improved workplace accommodations and benefits, present an opportunity to improve cancer survivorship. Female adolescent and young adult cancer survivors can be particularly vulnerable to adverse employment and financial outcomes. Those with cancer‐related employment disruption report increased financial hardship related to material conditions and psychological distress. [ABSTRACT FROM AUTHOR]

Background: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability.Methods: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling.Results: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%).Conclusions: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education. [ABSTRACT FROM AUTHOR]

Background: Relative to the general population, cancer patients and survivors may have an elevated risk of mortality from noncancer causes, such as cardiovascular disease and infections, but few studies have examined rates of noncancer mortality among patients diagnosed as adolescents and young adults (AYAs) (ages 15-39 years).Methods: The Surveillance, Epidemiology, and End Results database was used to identify AYA patients who were diagnosed with a first malignant cancer between 1973 and 2015. Rates of mortality from noncancer causes among AYAs with cancer were compared with those in the general US population using standardized mortality ratios (SMRs), adjusted for age, sex, race, and calendar year.Results: Among 235,541 AYAs with cancer, a total of 12,948 deaths from noncancer causes occurred over 3.1 million total person-years of follow-up. Overall, noncancer mortality was significantly increased among AYAs with cancer relative to the general population (SMR, 1.84; 95% CI, 1.80-1.87). SMRs were particularly elevated for infectious diseases (SMR, 5.13; 95% CI, 4.95-5.32), cardiovascular disease (SMR, 1.55; 95% CI, 1.50-1.60), and renal diseases (SMR, 2.40; 95% CI, 2.12-2.71). These associations persisted for more than 20 years after cancer diagnosis. Cancer types associated with the highest SMRs for all noncancer mortality included leukemias (SMR, 5.26), Hodgkin lymphoma (SMR, 3.12), non-Hodgkin lymphoma (SMR, 6.33), central nervous system tumors (SMR, 3.38), head and neck cancers (SMR, 2.09), and cervical/uterine cancers (SMR, 2.03).Conclusions: AYAs with cancer have an elevated burden of mortality from noncancer causes that persists many years after cancer diagnosis, highlighting the importance of comprehensive, long-term follow-up care for noncancer conditions throughout survivorship. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) risk is an important health concern among survivors of breast cancer. However, few studies to date have examined whether trajectories of CVD risk and major risk factors are worse among women with a breast cancer diagnosis compared with those without.Methods: Changes in weight, body mass index, waist circumference, systolic blood pressure, and 10-year CVD risk were compared between women with (813 women) and without (1049 women) an incident breast cancer diagnosis while they were enrolled in the National Institute of Environmental Health Sciences Sister Study cohort. Blood pressure and adiposity measures were collected by trained examiners at an enrollment visit (≥1 year before breast cancer diagnosis) and a second home visit 4 to 11 years later (≥1 year after breast cancer diagnosis). The non-laboratory-based Framingham risk score, a measure of 10-year general CVD risk, was calculated at both the enrollment and second visits. All analyses were stratified by menopausal status at the time of enrollment.Results: Women who were premenopausal at the time of enrollment experienced moderate increases in weight, waist circumference, systolic blood pressure, and CVD risk over the study period. Those who were postmenopausal at the time of enrollment demonstrated little change in weight, but were found to have increases in waist circumference, systolic blood pressure, and CVD risk. In both groups, changes over time did not differ significantly according to breast cancer status. Neither chemotherapy nor endocrine therapy were found to be associated with greater increases in CVD risk or risk factors.Conclusions: In the current study cohort, changes over time in CVD risk, adiposity measures, and blood pressure were similar between women who developed an incident breast cancer and those who did not. [ABSTRACT FROM AUTHOR]

Background: Many studies have examined long-term outcomes after childhood cancer, but few address outcomes for adolescent and young adult (AYA; those aged 15-39 years) cancer survivors. Conditional survival reflects changing mortality risk with time since cancer diagnosis and is a useful measure for planning long-term follow-up care.Methods: Using the Surveillance, Epidemiology, and End Results registry 9 database, the authors identified a cohort of AYA patients diagnosed with a first malignant cancer between 1973 and 2009 and followed through 2014. They estimated 5-year relative survival at the time of diagnosis and at each additional year survived up to 25 years after diagnosis, conditional on the individual being alive at the beginning of that year.Results: A total of 205,954 AYA patients with cancer were identified. Thyroid cancer, melanoma, testicular cancer, breast cancer, lymphoma, leukemia, and central nervous system (CNS) tumors comprised 67% of all cancers. For all cancers combined, 5-year relative survival was 84.5% (95% confidence interval, 84.3%-84.7%) at 1 year after diagnosis and 94.0% (95% CI, 93.9%-94.2%) at 5 years. The relative survival first exceeded 95%, reflecting minimal excess mortality compared with the general population, at 7 years. Patients with thyroid cancer, testicular cancer, melanoma, and breast cancer reached a relative survival of >95% at the time of diagnosis and at 1, 3, and 18 years after diagnosis, respectively. Estimates for those with Hodgkin lymphoma and leukemia were >95% at 6 and 13 years, respectively, but declined to <95% at 20 years. AYA individuals with CNS tumors did not reach 95% by 25 years after diagnosis.Conclusions: For AYA survivors of breast cancer, CNS tumors, and hematologic malignancies, long-term excess mortality should be considered when planning follow-up care. Cancer 2018;124:3037-43. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Greater body mass index (BMI), a measure of overall adiposity, is associated with a higher risk of postmenopausal breast cancer. The role of central adiposity, often measured by waist circumference, is less well understood, especially among premenopausal women. The objective of the current study was to examine multiple measures of adiposity in relation to breast cancer in a prospective cohort study.Methods: A total of 50,884 Sister Study cohort participants aged 35 to 74 years were enrolled from 2003 through 2009. Inclusion criteria for the cohort included having a sister previously diagnosed with breast cancer. Trained study personnel measured height, weight, and waist and hip circumference during a home visit and study participants completed a detailed questionnaire. Using Cox regression analysis, we estimated multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with adiposity measurements, considering tumor subtype and menopausal status.Results: In total, 2009 breast cancers were diagnosed during follow-up (mean = 5.4 years). Weight, BMI, waist circumference, and waist-to-hip ratio were found to be positively associated with overall breast cancer risk and HRs were greater among postmenopausal women, those with hormonally responsive tumors, and women who were not currently using postmenopausal hormones. In models that adjusted for BMI, waist circumference associations persisted among both postmenopausal women (81-88 cm vs ≤80 cm: HR = 1.16 [95% CI 1.01-1.35] and >88 cm vs ≤80 cm: HR = 1.30 [95% CI 1.10-1.54]) and premenopausal women (81-88 cm vs ≤80 cm: HR = 1.56 [95% CI 1.19-2.04] and >88 cm vs ≤80 cm: HR = 1.30 [95% CI 0.91-1.87]).Conclusions: Findings from this large, prospective study with examiner-measured body size indicate that waist circumference is independently and positively associated with both premenopausal and postmenopausal breast cancer risk. [ABSTRACT FROM AUTHOR]