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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: The dominant invasive breast cancer histologic subtype, ductal carcinoma, shows intrinsic subtype diversity. However, lobular breast cancers are predominantly Luminal A. Both histologic subtypes show distinct relationships with patient and tumor characteristics, but it is unclear if these associations remain after accounting for intrinsic subtype.Methods: Generalized linear models were used to estimate relative frequency differences (RFDs) and 95% confidence intervals (95% CIs) for the associations between age, race, tumor characteristics, immunohistochemistry (IHC) and RNA-based intrinsic subtype, TP53 status, and histologic subtype in the Carolina Breast Cancer Study (CBCS, n = 3,182) and The Cancer Genome Atlas (TCGA, n = 808).Results: Relative to ductal tumors, lobular tumors were significantly more likely to be Luminal A [CBCS RNA RFD: 44.9%, 95% CI (39.6, 50.1); TCGA: RFD: 50.5%, 95% CI (43.9, 57.1)], were less frequent among young (≤ 50 years) and black women, were larger in size, low grade, less frequently had TP53 pathway defects, and were diagnosed at later stages. These associations persisted among Luminal A tumors (n = 242).Conclusions: While histology is strongly associated with molecular characteristics, histologic associations with age, race, size, grade, and stage persisted after restricting to Luminal A subtype. Histology may continue to be clinically relevant among Luminal A breast cancers. [ABSTRACT FROM AUTHOR]

Purpose: Annually, > 45,000 US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics.Methods: We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15-39 during 2000-2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression.Results: Among 17,564 AYA cancer survivors, 1989 had ≥ 1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007-2012, compared to 9.4% during 2000-2005 (HR = 1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006.Conclusions: Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15 years.Implications For Cancer Survivors: Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: A cancer diagnosis in adolescence and young adulthood (AYA, ages 15–39) may affect future pregnancy outcomes. Previous studies have reported an increased risk of preterm delivery (< 37 weeks of gestation) after maternal cancer treatment. In this analysis, we evaluated whether non-cancer characteristics modify the association between an AYA cancer history and preterm birth.Methods: North Carolina Central Cancer Registry records (2000–2013) were linked to state birth certificate files (2000–2014) to identify births to AYA cancer survivors (n = 1,980). A comparison cohort of births to women without a cancer diagnosis was selected from birth certificate files (n = 11,860). Log-binomial regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. Effect modification by early prenatal care (1st trimester; yes/no), race/ethnicity (white/black/other), previous live births (0/1+), maternal age (< 25/25–29/30–34/35+), smoking during pregnancy (any/none), and education (high school or less/some college/Bachelor’s degree or higher) was evaluated using likelihood ratio tests (LRT).Results: Overall, preterm births were more common among AYA survivors than the comparison group (RR = 1.24, CI 1.07–1.43). The association was stronger among those who did not receive early prenatal care (RR = 1.73, CI 1.26–2.37) than among those who did (RR = 1.15, CI 0.98–1.35; LRT p = 0.03). Maternal age < 25 was also associated with a greater increase in preterm birth (< 25: RR = 1.80, CI 1.27–2.54; LRT p = 0.07). Associations did not vary strongly by other factors evaluated.Conclusions: An AYA cancer diagnosis may be associated with an increased risk of preterm birth, particularly among women who are younger and receive late or no prenatal care. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype.Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+).Results: In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype.Conclusions: Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: Women may have incomplete understanding of a breast cancer diagnosis, leading to inaccurate reporting in epidemiological studies. However, it is not feasible to obtain consent for medical records from all women participating in a study. Therefore, it is important to determine how well self-reported breast cancer characteristics correspond with what is found in medical records, but few studies have evaluated agreement of self-reported breast cancer characteristics with abstracted medical records.Methods: We calculated the positive predictive value (PPV) of self-reports compared to medical records and explored whether participant characteristics may have influenced reporting accuracy. We analyzed data from 2518 reported breast cancer cases from the Sister Study, a large nationwide cohort of women with a family history of breast cancer.Results: Medical records or pathology reports were obtained for 2066 of 2518 (82%) women who reported incident breast cancer. Breast cancer was confirmed for over 99% (n = 2054) of women with medical records. Confirmation rates were high for invasive, ductal, hormone receptor positive, and HER2 negative breast cancers, with little variation by race/ethnicity or age. Self-reported in situ breast cancer had a lower PPV (64.2%), with medical records showing invasive breast cancer instead, especially for older and Hispanic women. Hormone receptor (ER and PR) negative and HER2 positive self-reports had lower PPVs (83.0%, 71.6%, and 66.1% respectively). Hispanic women and women ages 65 or older at diagnosis were less able to accurately report breast cancer stage, excluding stage I.Conclusions: Accuracy of reporting overall breast cancer and common subtypes is high. Despite having a family history of breast cancer and voluntarily enrolling in a study evaluating breast cancer risk factors, participants may have greater difficulty distinguishing between in situ and invasive breast cancer and may less accurately report other less common subtypes. Discrepancies may reflect women's poor understanding of information conveyed by health care providers or lack of consistent terminology used to describe subtypes. [ABSTRACT FROM AUTHOR]

Expanding research capacity of large research networks within health care delivery systems requires strategically training both embedded and external investigators in necessary skills for this purpose. Researchers new to these settings frequently lack the skills and specialized knowledge conducive to multi-site and multi-disciplinary research set in delivery systems. This report describes the goals and components of the Cancer Research Network (CRN) Scholars Program, a 26-month training program developed to increase the capacity for cancer research conducted within the network's participating sites, its progression from training embedded investigators to a mix of internal and external investigators, and the content evolution of the training program. The CRN Scholars program was launched in 2007 to assist junior investigators from member sites develop independent and sustainable research programs within the CRN. Resulting from CRN's increased emphasis on promoting external collaborations, the 2013 Scholars program began recruiting junior investigators from external institutions committed to conducting delivery system science. Based on involvement of this broader population and feedback from prior Scholar cohorts, the program has honed its focus on specific opportunities and issues encountered in conducting cancer research within health care delivery systems. Efficiency and effectiveness of working within networks is accelerated by strategic and mentored navigation of these networks. Investing in training programs specific to these settings provides the opportunity to improve multi-disciplinary and multi-institutional collaboration, particularly for early-stage investigators. Aspects of the CRN Scholars Program may help inform others considering developing similar programs to expand delivery system research or within large, multi-disciplinary research networks. [ABSTRACT FROM AUTHOR]

Among women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC. Using data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004–2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors. Adjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals. Findings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT. [ABSTRACT FROM AUTHOR]

Background: Parity and time since last birth influence breast cancer risk and vary by intrinsic tumor subtype, but the independent effects of these factors on prognosis have received limited attention. Methods: Study participants were 1,140 invasive breast cancer patients from phases I and II of the population-based Carolina Breast Cancer Study, with tissue blocks available for subtyping using immunohistochemical markers. Breast cancer risk factors, including pregnancy history, were collected via in-person interviews administered shortly after diagnosis. Vital status was determined using the National Death Index. The association of parity and birth recency with breast cancer-specific and overall survival was assessed using Cox proportional hazards models. Results: During follow-up (median =13.5 years), 450 patients died, 61% due to breast cancer (n = 276). High parity (3þ births) and recent birth (<5 years before diagnosis) were positively associated with breast cancer-specific mortality, independent of age, race, and selected socioeconomic factors [parity, reference = nulliparous, adjusted HR = 1.76; 95% confidence interval (CI) = 1.13-2.73; birth recency, reference = 10þ years, adjusted HR = 1.29; 95% CI, 0.79-2.11]. The associations were stronger among patients with luminal tumors and those surviving longer than 5 years. Conclusions: Parity and recent birth are associated with worse survival among breast cancer patients, particularly among luminal breast cancers and long-term survivors. Impact: The biologic effects of parity and birth recency may extend from etiology to tumor promotion and progression. [ABSTRACT FROM AUTHOR]

[Display omitted] Light at night (LAN) may alter estrogen regulation through circadian disruption. High levels of outdoor LAN may increase breast cancer risk, but studies have largely not considered possible residual confounding from correlated environmental exposures. We evaluated the association between indoor and outdoor LAN and incident breast cancer. In 47,145 participants in the prospective Sister Study cohort living in the contiguous U.S., exposure to outdoor LAN was determined using satellite-measured residential data and indoor LAN was self-reported (light/TV on, light from outside the room, nightlight, no light). We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between outdoor and indoor LAN and breast cancer risk. Models were adjusted for age, race/ethnicity, educational attainment, annual household income, neighborhood disadvantage, latitude, and population density as a proxy for urbanicity. To evaluate the potential for residual confounding of the outdoor LAN and breast cancer relationship by factors associated with urbanicity, we considered further adjustment for exposures correlated with outdoor LAN including NO 2 [Spearman correlation coefficient, rho (ρ) = 0.78], PM 2.5 (ρ = 0.36), green space (ρ = − 0.41), and noise (ρ = 0.81). During 11 years of follow-up, 3,734 breast cancer cases were identified. Outdoor LAN was modestly, but non-monotonically, associated with a higher risk of breast cancer (Quintile 4 vs 1: HR = 1.10, 95% CI: 0.99–1.22; Quintile 5 vs 1: HR = 1.04, 95% CI: 0.93–1.16); however, no association was evident after adjustment for correlated ambient exposures (Quintile 4 vs 1: HR = 0.99, 95% CI: 0.86–1.14; Quintile 5 vs 1: HR = 0.89, 95% CI: 0.74–1.06). Compared to those with no indoor LAN exposure, sleeping with a light or TV on was associated with a HR = 1.09 (95% CI: 0.97–1.23) in the adjusted model. Outdoor LAN does not appear to increase the risk of breast cancer after adjustment for correlated environmental exposures. [ABSTRACT FROM AUTHOR]