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Purpose: Lower extremity lymphedema (LEL), which causes ankle, leg, and feet swelling, poses a significant challenge for endometrial cancer survivors, impacting physical functioning and psychological well-being. Inconsistent LEL diagnostic methods result in wide-ranging LEL incidence estimates. Methods: We calculated the cumulative incidence of LEL based on survivor-reported Gynecologic Cancer Lymphedema Questionnaire (GCLQ) responses in addition to survivor- and nurse-reported leg circumference measurements among a pilot sample of 50 endometrial cancer survivors (27 White, 23 Black) enrolled in the ongoing population-based Carolina Endometrial Cancer Study. Results: Self-leg circumference measurements were perceived to be difficult and were completed by only 17 survivors. Diagnostic accuracy testing measures (sensitivity, specificity, positive and negative predictive value) compared the standard nurse-measured ≥ 10% difference in leg circumference measurements to GCLQ responses. At a mean of ~11 months post-diagnosis, 54% of survivors met established criteria for LEL based on ≥ 4 GCLQ cutpoint while 24% had LEL based on nurse-measurement. Percent agreement, sensitivity, and specificity approximated 60% at a threshold of ≥ 5 GCLQ symptoms. However, Cohen's kappa, a measure of reliability that corrects for agreement by chance, was highest at ≥ 4 GCLQ symptoms (κ = 0.27). Conclusion: Our findings emphasize the need for high quality measurements of LEL that are feasible for epidemiologic study designs among endometrial cancer survivors. Future studies should use patient-reported survey measures to assess lymphedema burden and quality of life outcomes among endometrial cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Cancer survivors have increased risk of endocrine complications, but there is a lack of information on the occurrence of specific endocrinopathies at the population-level. Methods: We used data from the California Cancer Registry (2006–2018) linked to statewide hospitalisation, emergency department, and ambulatory surgery databases. We estimated the cumulative incidence of and factors associated with endocrinopathies among adolescents and young adults (AYA, 15–39 years) who survived ≥2 years after diagnosis. Results: Among 59,343 AYAs, 10-year cumulative incidence was highest for diabetes (4.7%), hypothyroidism (4.6%), other thyroid (2.2%) and parathyroid disorders (1.6%). Hypothyroidism was most common in Hodgkin lymphoma, leukaemia, breast, and cervical cancer survivors, while diabetes was highest among survivors of leukaemias, non-Hodgkin lymphoma, colorectal, cervical, and breast cancer. In multivariable models, factors associated with increased hazard of endocrinopathies were treatment, advanced stage, public insurance, residence in low/middle socioeconomic neighbourhoods, older age, and non-Hispanic Black or Hispanic race/ethnicity. Haematopoietic cell transplant was associated with most endocrinopathies, while chemotherapy was associated with a higher hazard of ovarian dysfunction and hypothyroidism. Conclusions: We observed a high burden of endocrinopathies among AYA cancer survivors, which varied by treatment and social factors. Evidence-based survivorship guidelines are needed for surveillance of these diseases. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. Methods: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. Results: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED βQ4vsQ1: − 0.17, 95% CI − 0.27, − 0.08; DASH βQ4vsQ1: − 0.18, 95% CI − 0.28, − 0.08; aHEI βQ4vsQ1: − 0.20, 95% CI − 0.30, − 0.10; HEI-2015 βQ4vsQ1: − 0.19, 95% CI − 0.29, − 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. Conclusion: Healthy dietary patterns were associated with lower levels of oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Breast cancer chemotherapy utilization not only may differ by race and age, but also varies by genomic risk, tumor characteristics, and patient characteristics. Studies in demographically diverse populations with both clinical and genomic data are necessary to understand potential disparities by race and age. Methods: In the Carolina Breast Cancer Study Phase 3 (2008–2013), chemotherapy receipt (yes/no) and regimen type were assessed in association with age and race among hormone receptor (HR) positive and HER2-negative tumors (n = 1862). Odds ratios were estimated for the association between demographic factors and chemotherapy receipt. Results: Monotonic decreases in frequency of adjuvant chemotherapy receipt were observed over time during the study period, while neoadjuvant chemotherapy was stable. Younger age was associated with chemotherapy receipt (OR [95% CI]: 2.9 [2.4, 3.6]) and with anthracycline-based regimens (OR [95% CI]: 1.7 [1.3, 2.4]). Participants who had Medicaid (OR [95% CI]: 1.8 [1.3, 2.5]), lived in rural settings (OR [95% CI]: 1.4 [1.0, 2.0]), or were Black (OR [95% CI]: 1.5 [1.2, 1.8]) had slightly higher odds of chemotherapy, but these associations were non-significant with adjustment for stage and grade. Associations between younger age and chemotherapy receipt were strongest among women who did not receive genomic testing. Conclusions: While race was not strongly associated with chemotherapy receipt, younger age remains a strong predictor of chemotherapy receipt, even with adjustment for clinical factors and among women who receive genomic testing. [ABSTRACT FROM AUTHOR]

Background: Adolescent and young adult (AYA) cancer survivors are at an elevated risk of financial hardship. However, financial hardship among LGBTQ+ AYAs has not been widely explored. Thus, we used qualitative and quantitative survey data from the Horizon Study cohort to assess financial hardship of AYAs by LGBTQ+ status. Methods: Multivariable logit models, predicted probabilities, average marginal effects or differences in predicted probabilities (AME) and 95% confidence intervals (CI) were used to assess the association of LGBTQ+ status and two components of financial hardship: material and psychological. Qualitative content analysis of an open-ended survey question about financial sacrifices was used to describe the third component of financial hardship, behavioral. Results: Among 1,635 participants, 4.3% self-identified as LGBTQ+. Multivariable logit models controlling for demographic factors revealed that LGBTQ+ AYAs had an 18-percentage point higher probability of experiencing material financial hardship (95%CI 6–30%) and a 14-percentage point higher probability of experiencing psychological financial hardship (95%CI 2–26%) than non-LGBTQ+ AYAs. Controlling for economic factors attenuated the association of LGBTQ+ status with psychological financial hardship (AME = 11%; 95%CI – 1–23%), while the material financial hardship association remained statistically significant (AME = 14%; 95%CI 3–25%). In the qualitative analysis, LGBTQ+ AYAs frequently reported educational changes and costs (e.g., quitting school), unpaid bills and debt (e.g., medical debt, taking on credit card debt), as well as changes in housing and poor housing conditions (e.g., moving into less expensive house). Conclusions: LGBTQ + targeted and tailored interventions are needed to move toward equity for LGBTQ+ AYAs—an overlooked minority population. [ABSTRACT FROM AUTHOR]

Purpose: Women face multiple barriers to fertility preservation after cancer diagnosis, but few studies have examined disparities in use of these services. Methods: Women aged 15–39 years diagnosed with cancer during 2004–2015 were identified from the North Carolina Central Cancer Registry and linked to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Women who cryopreserved oocytes or embryos for fertility preservation (n = 96) were compared to women who received gonadotoxic treatment but did not use fertility preservation (n = 7964). Conditional logistic and log-binomial regression were used to estimate odds ratios (ORs) or prevalence ratios (PRs) and 95% confidence intervals (CIs). Results: Few adolescent and young adult women with cancer in our study (1.2%) used fertility preservation. In multivariable regression, women less likely to use fertility preservation were older at diagnosis (ages 25–29 vs. 35–39: OR = 6.27, 95% CI: 3.35, 11.73); non-Hispanic Black (vs. non-Hispanic White: PR = 0.44, 95% CI: 0.24, 0.79); and parous at diagnosis (vs. nulliparous: PR = 0.24, 95% CI: 0.13, 0.45); or lived in census tracts that were non-urban (vs. urban: PR = 0.12, 95% CI: 0.04, 0.37) or of lower socioeconomic status (quintiles 1–3 vs. quintiles 4 and 5: PR = 0.39, 95% CI: 0.25, 0.61). Conclusions: Women with cancer who were older, non-Hispanic Black, parous, or living in areas that were non-urban or of lower socioeconomic position were less likely to use fertility preservation. Implications for Cancer Survivors: Clinical and policy interventions are needed to ensure equitable access to fertility services among women facing cancer treatment–related infertility. [ABSTRACT FROM AUTHOR]

Purpose: Women with preeclampsia are more likely to deliver preterm. Reports of inverse associations between preeclampsia and breast cancer risk, and positive associations between preterm birth and breast cancer risk are difficult to reconcile. We investigated the co-occurrence of preeclampsia/gestational hypertension with preterm birth and breast cancer risk using data from the Premenopausal Breast Cancer Collaborative Group. Methods: Across 6 cohorts, 3096 premenopausal breast cancers were diagnosed among 184,866 parous women. We estimated multivariable hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal breast cancer risk using Cox proportional hazards regression. Results: Overall, preterm birth was not associated (HR 1.02, 95% CI 0.92, 1.14), and preeclampsia was inversely associated (HR 0.86, 95% CI 0.76, 0.99), with premenopausal breast cancer risk. In stratified analyses using data from 3 cohorts, preterm birth associations with breast cancer risk were modified by hypertensive conditions in first pregnancies (P-interaction = 0.09). Preterm birth was positively associated with premenopausal breast cancer in strata of women with preeclampsia or gestational hypertension (HR 1.52, 95% CI: 1.06, 2.18), but not among women with normotensive pregnancy (HR = 1.09, 95% CI: 0.93, 1.28). When stratified by preterm birth, the inverse association with preeclampsia was more apparent, but not statistically different (P-interaction = 0.2), among women who did not deliver preterm (HR = 0.82, 95% CI 0.68, 1.00) than those who did (HR = 1.07, 95% CI 0.73, 1.56). Conclusion: Findings support an overall inverse association of preeclampsia history with premenopausal breast cancer risk. Estimates for preterm birth and breast cancer may vary according to other conditions of pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Radiation therapy (RT) has been associated with decreased health-related quality of life (HRQOL) in clinical trials of early-stage endometrial cancer (EC), but few studies have examined the association in real-world settings. We assessed HRQOL associated with adjuvant RT for older women with early-stage EC within a large U.S. population-based registry resource. Methods: The Surveillance Epidemiology and End Results and the Medicare Health Outcomes Survey linkage (1998–2017) was used to identify women with early-stage EC aged ≥ 65 years at survey who received surgery and were diagnosed ≥ 1-year prior (n = 1,140). HRQOL was evaluated with the 36-item Short-Form Health Survey (SF-36) until 2006 and the Veterans RAND 12-Item Health Survey (VR-12) post 2006. Ordinary least squares regression was used to estimate mean difference (MD) in T scores and 95% confidence intervals (CIs) comparing treatment groups (surgery alone, adjuvant external beam radiation therapy [EBRT], or adjuvant vaginal brachytherapy [VBT]) after accounting for confounders using propensity score weighting. Results: Overall, RT was not associated with physical health (MD = 0.97; 95% CI = − 1.13, 3.07) or mental health (MD = − 0.78; 95% CI = − 2.60, 1.05) relative to surgery alone. In analyses by RT type, adjuvant VBT was associated with better general health on the SF-36/VR-12 subscale (MD = 3.59; 95% CI = 0.56, 6.62) relative to surgery alone. No statistically significant associations were observed for adjuvant VBT and physical or mental health, or for adjuvant EBRT and any HRQOL domain. Conclusion: Older women with early-stage EC treated with adjuvant RT did not report worse physical and mental HRQOL scores compared to those treated with surgery alone, though relevant symptoms should be evaluated further to fully understand the disease and treatment specific aspects of the HRQOL. [ABSTRACT FROM AUTHOR]

Purpose: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied. Methods: To describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18–45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use—including oocyte/embryo cryopreservation or embryo transfer—after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART use. Results: Among 36,468 women with invasive breast cancer, 206 (0.56%) used ART. Women significantly less likely to use ART were age 36–45 years at diagnosis (vs. 18–35 years: PR = 0.17, 95% CI 0.13–0.22); non-Hispanic Black or Hispanic (vs. non-Hispanic White: PR = 0.31, 95% CI 0.21–0.46); had at least one child (vs. no children: adjusted PR [aPR] = 0.39, 95% CI 0.25–0.60); or lived in non-urban areas (vs. urban: aPR = 0.28, 95% CI 0.10–0.75), whereas women more likely to use ART lived in high-SES areas (vs. low-/middle-SES areas: aPR = 2.93, 95% CI 2.04–4.20) or had private insurance (vs. public/other insurance: aPR = 2.95, 95% CI 1.59–5.49). Conclusion: Women with breast cancer who are socially or economically disadvantaged, or who already had a child, are substantially less likely to use ART after diagnosis. The implementation of policies or programs targeting more equitable access to fertility services for women with cancer is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation. Methods: From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35–74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of β-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were also measured. Since the biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF2α to prostaglandin F2α ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations. Results: Total plasma carotenoids were inversely associated with 8-iso-PGF2α-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and β-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF2α; Phighest vs. lowest quartile = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF2α, suggesting an additional anti-inflammatory effect. Supplemental β-carotene was inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF2α. Dietary carotenoids were not associated with either biomarker. Conclusion: Plasma carotenoids and supplemental β-carotene were associated with lower concentrations of 8-iso-PGF2α metabolite. Plasma carotenoids associations may reflect antioxidant effects. [ABSTRACT FROM AUTHOR]

Purpose: Functional status deficits are important quality of life concerns for older cancer survivors. We examined the prevalence of falls, walking/balance problems, and limitations in activities of daily living (ADLs) among older women with a history of endometrial cancer. Methods: Cancer registry records from the Surveillance, Epidemiology, and End Results (SEER) program linked with Medicare Health Outcomes Survey (MHOS) data were used to identify endometrial cancer survivors aged ≥ 65 years who completed a survey ≥ 1 year after their cancer diagnosis (N = 3766), as well as an age- and race-matched group of women without a cancer history (N = 3766). We estimated prevalence ratios (PRs) to compare the prevalence of falls, walking or balance problems, and limitations in ADLs (bathing, dressing, eating, getting in/out of chairs, walking, using the toilet) between groups. Results: Difficulty with walking or balance was more common among survivors than the noncancer group (43% vs 36%; PR = 1.19; 95% CI: 1.10–1.27). Fall prevalence was similar between groups (endometrial cancer: 25%; noncancer: 26%; PR = 0.98; 95% CI: 0.89–1.08). Nearly half of endometrial cancer survivors (47%) reported at least one ADL limitation, with several activities (getting in/out of a chair, walking, bathing, using the toilet) more often limited among survivors than among women without cancer. Conclusion: Functional impairments, especially problems with walking and/or balance, are common among older endometrial cancer survivors. Our results highlight the importance of addressing functional problems during the ongoing survivorship care of women with a history of endometrial cancer, with referral to rehabilitation or other relevant services when indicated. [ABSTRACT FROM AUTHOR]

Purpose: This study examines polypharmacy and prescription drug use patterns in cancer survivors, a growing population at risk for cancer sequelae and side effects from treatment, which can arise months or even years following diagnosis. Survivors may experience greater medication burden than the general population, increasing concerns for polypharmacy and subsequent risks of drug interactions and non-adherence. Methods: Using the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2014, we examined the association between a cancer history and presence of polypharmacy (5+ medications). We estimated prevalence ratios and prevalence differences for polypharmacy comparing those with and without a cancer history using binomial regression models and propensity score (PS) weighting to account for baseline differences between groups. Results: We identified 32,238 adults aged 20 years or older; 1899 had cancer (excluding non-melanoma skin) at least 1 year before the survey. Overall, polypharmacy prevalence was 13% and 35% in those with and without a cancer history, respectively. After PS weighting, the polypharmacy prevalence was 1.26 times higher among those with versus without a cancer history (weighted prevalence ratio, 1.26; 95% CI, 1.18, 1.35). In sub-group analyses, the weighted prevalence ratio was largest for those 20–39 years old at survey (2.78; 95% CI, 1.71, 4.53), and the weighted prevalence difference was largest for those 40–64 years old at survey (9.35%; 95% CI, 5.70%, 13.01%). Conclusions/Implications for Cancer Survivors: Cancer survivors of all ages take more medications than those without cancer history and may benefit from discussions with providers about age-tailored medication use management. [ABSTRACT FROM AUTHOR]

Purpose: To examine trends in the surgical treatment of breast cancer by age, rurality, and among Black women in a populous, racially diverse, state in the Southeastern United States of America. Methods: We identified women diagnosed with localized or regional breast cancer between 2003 and 2016 in the North Carolina Central Cancer Registry (n = 86,776). Using Joinpoint regression we evaluated the average annual percentage change in proportion of women treated with mastectomy versus breast-conserving surgery overall, by age group, among Black women, and for women residing in rural areas. Results: Overall, the rate of mastectomy usage in the population declined 2.5% per year between 2003 and 2016 (95% CI − 3.2, − 1.7). Over this same time interval, breast-conserving surgery increased by 1.6% per year (95% CI 0.9, 2.2). These temporal trends in surgery were also observed among Black women and rural residing women. Trends in surgery type varied by age group: mastectomy declined over time among women > 50 years, but not among women aged 18–49 at diagnosis. Discussion: In contrast to national studies that reported increasing use of mastectomy, we found declining mastectomy rates in the early 2000s in a Southern US state with a racially and geographically diverse population. These decreasing trends were consistent among key subgroups affected by cancer inequities, including Black and White rural women. [ABSTRACT FROM AUTHOR]

Purpose: To describe breast cancer treatment patterns among premenopausal women by age and time since last pregnancy. Methods: Data were analyzed from 1179 women diagnosed with premenopausal breast cancer in the Carolina Breast Cancer Study. Of these, 160 had a recent pregnancy (within 5 years of cancer diagnosis). Relative frequency differences (RFDs) and 95% confidence intervals (CIs) were used to compare cancer stage, treatment modality received, treatment initiation delay (> 30 days), and prolonged treatment duration (> 2 to > 8 months depending on the treatment received) by age and recency of pregnancy. Results: Recently postpartum women were significantly more likely to have stage III disease [RFD (95% CI) 12.2% (3.6%, 20.8%)] and to receive more aggressive treatment compared to nulliparous women. After adjustment for age, race and standard clinical tumor characteristics, recently postpartum women were significantly less likely to have delayed treatment initiation [RFD (95% CI) − 11.2% (− 21.4%, − 1.0%)] and prolonged treatment duration [RFD (95% CI) − 17.5% (− 28.0%, − 7.1%)] and were more likely to have mastectomy [RFD (95% CI) 14.9% (4.8%, 25.0%)] compared to nulliparous. Similarly, younger women (< 40 years of age) were significantly less likely to experience prolonged treatment duration [RFD (95% CI) − 5.6% (− 11.1%, − 0.0%)] and more likely to undergo mastectomy [RFD (95% CI) 10.6% (5.2%, 16.0%)] compared to the study population as a whole. Conclusion: These results suggest that recently postpartum and younger women often received prompt and aggressive breast cancer treatment. Higher mortality and recurrence among recently pregnant women are unlikely to be related to undertreatment. [ABSTRACT FROM AUTHOR]

Purpose: Black women have a 40% increased risk of breast cancer-related mortality. These outcome disparities may reflect differences in tumor pathways and a lack of targetable therapies for specific subtypes that are more common in Black women. Hepatocyte growth factor (HGF) is a targetable pathway that promotes breast cancer tumorigenesis, is associated with basal-like breast cancer, and is differentially expressed by race. This study assessed whether a 38-gene HGF expression signature is associated with recurrence and survival in Black and non-Black women. Methods: Study participants included 1957 invasive breast cancer cases from the Carolina Breast Cancer Study. The HGF signature was evaluated in association with recurrence (n = 1251, 171 recurrences), overall, and breast cancer-specific mortality (n = 706, 190/328 breast cancer/overall deaths) using Cox proportional hazard models. Results: Women with HGF-positive tumors had higher recurrence rates [HR 1.88, 95% CI (1.19, 2.98)], breast cancer-specific mortality [HR 1.90, 95% CI (1.26, 2.85)], and overall mortality [HR 1.69; 95% CI (1.17, 2.43)]. Among Black women, HGF positivity was significantly associated with higher 5-year rate of recurrence [HR 1.73; 95% CI (1.01, 2.99)], but this association was not significant in non-Black women [HR 1.68; 95% CI (0.72, 3.90)]. Among Black women, HGF-positive tumors had elevated breast cancer-specific mortality [HR 1.80, 95% CI (1.05, 3.09)], which was not significant in non-Black women [HR 1.52; 95% CI (0.78, 2.99)]. Conclusion: This multi-gene HGF signature is a poor-prognosis feature for breast cancer and may identify patients who could benefit from HGF-targeted treatments, an unmet need for Black and triple-negative patients. [ABSTRACT FROM AUTHOR]

Purpose: Surgery is an important part of early stage breast cancer treatment that affects overall survival. Many studies of surgical treatment of breast cancer rely on data sources that condition on continuous insurance coverage or treatment at specified facilities and thus under-sample populations especially affected by cancer care inequities including the uninsured and rural populations. Statewide cancer registries contain data on first course of cancer treatment for all patients diagnosed with cancer but the accuracy of these data are uncertain. Methods: Patients diagnosed with stage I–III breast cancer between 2003 and 2016 were identified using the North Carolina Central Cancer Registry and linked to Medicaid, Medicare, and private insurance claims. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and Kappa statistics for receipt of surgery and type of surgery (breast conserving surgery or mastectomy) using the insurance claims as the presumed gold standard. Analyses were stratified by race, insurance type, and rurality. Results: Of 26,819 patients who met eligibility criteria, 23,125 were identified as having surgery in both the claims and registry for a sensitivity of 97.9% (95% CI 97.8%, 98.1%). There was also strong agreement for surgery type between the cancer registry and the insurance claims (Kappa: 0.91). Registry treatment data validity was lower for Medicaid insured patients than for Medicare and commercially insured patients. Conclusions: Cancer registry treatment data reliably identified receipt and type of breast cancer surgery. Cancer registries are an important source of data for understanding cancer care in underrepresented populations. [ABSTRACT FROM AUTHOR]

Purpose: Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks' gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects. Methods: Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004–2013 (Texas), 2004–2016 (Massachusetts and North Carolina), and 2004–2017 (New York) were classified by ET and FHB. Major birth defects were reported by statewide registries within the first year of life. Logistic regression was used to estimate adjusted odds ratios (AORs) and 95% CIs of the risks of a major nonchromosomal birth defect, small-for-gestational age birthweight (SGA), low birthweight (LBW), and preterm birth (≤36 weeks), by excess ET, and excess ET + excess FHB, by plurality at birth (singletons and twins). Results: In singletons with [2 ET, FHB =1] and [≥3 ET, FHB=1], risks [AOR (95% CI)] were increased, respectively, for major nonchromosomal birth defects [1.13 (1.00–1.27) and 1.18 (1.00–1.38)], SGA [1.10 (1.03–1.17) and 1.15 (1.05–1.26)], LBW [1.09 (1.02–1.13) and 1.17 (1.07–1.27)], and preterm birth [1.06 (1.00–1.12) and 1.14 (1.06–1.23)]. With excess ET + excess FHB, risks of all adverse outcomes except major nonchromosomal birth defects increased further for both singletons and twins. Conclusion: Excess embryos transferred are associated with increased risks for nonchromosomal birth defects, reduced birthweight, and prematurity in IVF-conceived births. [ABSTRACT FROM AUTHOR]

Purpose: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women. Methods: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression. Results: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89–0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85–0.90 for breast cancer overall and after menopause (p ≤ 0.02). Conclusions: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies. [ABSTRACT FROM AUTHOR]

Purpose: In the United States, hysterectomies and oophorectomies are frequently performed before menopause for benign conditions. The procedures are associated with reduced breast cancer-specific mortality among White women. The relationship between premenopausal gynecologic surgery and mortality in Black women with breast cancer is unknown.Methods: This investigation used incident invasive cases of breast cancer from Phases 1 and 2 of the Carolina Breast Cancer Study a population-based study that recruited Black and White women in North Carolina between 1993 and 2001. Premenopausal gynecologic surgery was operationalized in three categories: no surgery; hysterectomy with bilateral oophorectomy; hysterectomy with conservation of ≥ 1 ovary. Mortality was ascertained using the National Death Index, last updated in 2016. Multivariable-adjusted Cox Proportional Hazard Models were used to estimate the effect of premenopausal surgery on breast cancer-specific and all-cause mortality RESULTS: Hysterectomy with bilateral oophorectomy was associated with reduced breast cancer-specific mortality (HR 0.68; 95% CI 0.49, 0.96). White and Black women had a similar reduction in breast cancer-specific mortality. (HR among white: 0.66; 95% CI 0.43, 1.02), (HR among Black: 0.67; 95% CI 0.37, 1.21).Conclusions: There was a similar reduction in breast cancer-specific mortality following premenopausal, pre-diagnosis hysterectomy with bilateral oophorectomy across both Black and White women. [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]

Purpose: An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life.Methods: Sister study participants (n = 50,884) aged 35-74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk.Results: During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00-1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01-1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR = 1.44, 95% CI 1.02-2.02; 1940-1949, HR = 1.28, 95% CI 1.01-1.62).Conclusion: In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort. [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]

Purpose: Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers.Methods: Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort. Tumor characteristics and endocrine therapy use were collected from medical and prescription records. We calculated multivariable prevalence ratios (PR) and 95 % confidence intervals (CI) for the association of endocrine therapy (versus no endocrine therapy) and urinary incontinence, overall and by therapy type (tamoxifen or aromatase inhibitors). PROMIS Sexual Function and Satisfaction domain scores were compared across endocrine therapy groups.Results: Among the 548 women with a breast cancer diagnosis, 49 % received endocrine therapy. Overall, 18 % of women reported urinary incontinence symptoms. We observed no association between urinary incontinence and endocrine therapy use overall (PR = 0.97; 95 % CI 0.67, 1.43), tamoxifen (PR = 1.20; 95 % CI 0.74, 1.96), or aromatase inhibitors (PR = 0.89; 95 % CI 0.55, 1.42), compared to no use. Approximately 55 % of women were sexually active. Sexual function scores did not vary according to endocrine therapy use, although urinary incontinence was associated with lower satisfaction scores (p = 0.05).Conclusions: Our findings demonstrate a high prevalence of urinary incontinence after breast cancer diagnosis similar to the overall prevalence in older U.S. women, and this did not vary strongly according to use of endocrine therapy. [ABSTRACT FROM AUTHOR]

Purpose: Adiposity has been linked with increased breast cancer risk and mortality. It is established that etiologic associations for adiposity vary by tumor subtype, but the influence of adiposity on subtype-specific survival is unknown. Methods: Study participants were 1,109 invasive breast cancer participants in the population-based Carolina Breast Cancer Study, diagnosed between 1993 and 2001, and with tissue blocks available for immunohistochemical subtyping. General and central adiposities were assessed by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, based on in-person measurements after diagnosis. Vital status as of 2011 was determined using the National Death Index (median follow-up = 13.5 years). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer (BC)-specific and all-cause mortalities. Results: Among all patients, high WHR (≥0.84), but not BMI, was associated with all-cause mortality (adjusted HR 1.50, 95% CI 1.11-2.05, <0.77 as reference). No significant association between adiposity and BC-specific mortality was detected, although there was a suggestion of increased mortality risk among high-BMI (≥30 kg/m(2)) patients with basal-like tumors (adjusted HR 2.44, 95% CI 0.97-6.12, <25 kg/m(2) as reference). Quantitative differences in all-cause mortality were observed by subtype, with BMI associated with basal-like mortality and WHR associated with luminal mortality. The associations were attenuated by tumor characteristics. Conclusions: Our study confirms the association of adiposity and unfavorable overall survival in breast cancer patients and suggests that this association may vary by intrinsic subtype and adiposity measure. [ABSTRACT FROM AUTHOR]

Background: We evaluated students' perception of cancer causation among sixth-grade girls living in Wisconsin. Method: We asked female students to list up to 3 causes of cancer in a cross-sectional health survey. Results: A total of 141 answers were given by 53 students. The most frequently listed causes of cancer were cigarette smoking (91%), drugs (32%), an unhealthy diet (25%), and heredity (25%). Less than 10% of students listed other potentially modifiable risk factors such as exercise, sun exposure, or alcohol consumption. Conclusion: Students in this study appeared to link a range of high-risk behaviors with health consequences, although the specific health risks may not be understood. [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]