Yunan Han

ImportanceBreast cancer in young women has a less favorable prognosis compared with older women. Yet, comprehensive data on recent trends and how period and cohort effects may affect these trends among young women are not well-known.ObjectiveTo evaluate breast cancer incidence among young women in the US over a 20-year period by race and ethnicity, hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]), tumor stage, and age at diagnosis, as well as how period and cohort effects may affect these trends.Design, Setting, and ParticipantsThis cross-sectional study used data from Surveillance, Epidemiology, and End Results 17 registries (2000-2019). Women aged 20 to 49 years with a primary invasive breast cancer were included. Data were analyzed between February and June 2023.Main Outcomes and MeasuresAge-standardized incidence rates (ASIR), incidence …

Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and all were of moderate to high quality with NOS scores ranging from 5 to 8. We included 17 studies (11 case-control, 6 cohort) in final analysis. In case-control studies, weight gain after age 18 was …

PurposeTo examine the association of marital status with prostate cancer outcomes in a racially-diverse cohort.MethodsThe study population consisted of men (1010 Black; 1070 White) with incident prostate cancer from the baseline North Carolina-Louisiana Prostate Cancer (PCaP) cohort. Marital status at time of diagnosis and screening history were determined by self-report. The binary measure of marital status was defined as married (including living as married) vs. not married (never married, divorced/separated, or widowed). High-aggressive tumors were defined using a composite measure of PSA, Gleason Score, and stage. Definitive treatment was defined as receipt of radical prostatectomy or radiation. Multivariable logistic regression was used to examine the association of marital status with (1) high-aggressive tumors, (2) receipt of definitive treatment, and (3) screening history among Black and White men …

IntroductionObesity and proinflammatory conditions are associated with increased risks of cancer. The associations of baseline allostatic load with cancer mortality and whether this association is modified by body mass index (BMI) were examined.MethodsA retrospective analysis was performed in March–September 2022 using National Health and Nutrition Examination Survey years 1988 through 2010 linked with the National Death Index through December 31, 2019. Fine and Gray Cox proportional hazard models were stratified by BMI status to estimate subdistribution hazard ratios of cancer death between high and low allostatic load status (adjusted for age, sociodemographics, and health factors).ResultsIn fully adjusted models, high allostatic load was associated with a 23% increased risk of cancer death (adjusted subdistribution hazard ratio=1.23; 95% CI=1.06, 1.43) among all participants, a 3% increased …

PurposeDisparities in breast cancer survival have been observed within marginalized racial/ethnic groups and within the rural–urban continuum for decades. We examined whether there were differences among the intersectionality of race/ethnicity and rural residence on breast cancer outcomes.MethodsWe performed a retrospective analysis among 739,448 breast cancer patients using Surveillance Epidemiology and End Results (SEER) 18 registries years 2000 through 2016. We conducted multilevel logistic-regression and Cox proportional hazards models to estimate adjusted odds ratios (AORs) and hazard ratios (AHRs), respectively, for breast cancer outcomes including surgical treatment, radiation therapy, chemotherapy, late-stage disease, and risk of breast cancer death. Rural was defined as 2013 Rural–Urban Continuum Codes (RUCC) of 4 or greater.ResultsCompared with non-Hispanic white–urban …

Introduction: Current cancer research recognizes that early life factors are important risk factors for breast cancer. Studies suggest that weight gain after age 18 plays a role in the development of breast cancer; however, the research related to their association is inconsistent. Thus, we performed a meta-analysis to evaluate the associations between weight gain after age 18 and risk of breast cancer and to clarify whether there is heterogeneity stratified by menopausal status. Methods: We performed a comprehensive literature search of all relevant studies published prior to February 19, 2021, according to the established inclusion criteria, utilizing Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov. Two reviewers independently reviewed the articles for final inclusion. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies. Summary risk estimates (REs) with the …

The stomach is a complex and physiologically necessary organ, yet large differences in physiology between mouse and human stomachs have impeded translation of physiological discoveries and drug screens performed using murine gastric tissues. Gastric cancer (GC) is a global health threat, with a high mortality rate and limited treatment options. The heterogeneous nature of GC makes it poorly suited for current “one size fits all” standard treatments. In this review, we discuss the rapidly evolving field of gastric organoids, with a focus on studies expanding cultures from primary human tissues and describing the benefits of mouse organoid models. We introduce the differing methods for culturing healthy gastric tissue from adult tissues or pluripotent stem cells, discuss the promise these systems have for preclinical drug screens, and highlight applications of organoids for precision medicine. Finally, we discuss the …

12062Background: Pain symptoms are common in cancer survivors. The life expectancy of US cancer survivors continues to raise. To date, the comprehensive pattern of pain symptoms in US cancer survivors by cancer history remains unknown. Methods: Data on pain symptoms and correlates were derived from a nationally representative sample of cancer survivors (n = 55,716, weighted population = 17,352,886) in the 1997-2018 National Health Interview Survey. Individuals who answered “yes” to the questions “During the past three months, did you have headache/facial/neck/low back pain/low back pain radiating to the leg” were considered as having pain symptoms at respective anatomical regions. The US national prevalence of pain overall and by anatomical regions were estimated. Correlates of pain symptoms were examined using multivariable logistic regression. Results: The prevalence of overall pain …

ImportanceConsidering reported rural-urban cancer incidence and mortality trends, rural-urban cancer survival trends are important for providing a comprehensive description of cancer burden. Furthermore, little is known about rural-urban differences in survival trends by racial and ethnic groups.ObjectiveTo examine national rural-urban trends in 5-year cancer-specific survival probabilities for lung, prostate, breast, and colorectal cancers in a diverse sample of racial and ethnic groups.Design, Setting, and ParticipantsThis cross-sectional study used an epidemiologic assessment with 1975 to 2016 Surveillance, Epidemiology, and End Results (SEER) data to analyze patients diagnosed no later than 2011. Patients were classified as living in rural and urban counties based on the 2013 Rural-Urban Continuum Codes.Main Outcomes and MeasuresThe 5-year cancer-specific survival probability of urban and rural …

ImportanceFamily history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood.ObjectivesTo investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements.Design, Setting, and ParticipantsThis single-center cohort study examined 2 retrospective cohorts: a discovery set of 375 premenopausal women and a validation set of 14 040 premenopausal women. Data from women in the discovery set was collected between December 2015 and October 2016, whereas data from women in the validation set was collected between June 2010 and December 2015. Data analysis was performed between June 2018 and June 2020.ExposuresFamily history of breast cancer …

Background: Racial disparities persist in colorectal cancer (CRC) incidence and survival despite advances in screening and therapeutic options. While the liver and lung are often described as common sites for CRC metastasis, the effect of race and ethnicity on the presentation of metastases remains largely unexplored. In this study, we investigate the racial differences in metastatic patterns of de novo stage IV CRC and associate these patterns with racial differences in CRC mortality. Methods: This retrospective cohort study used 18 Surveillance, Epidemiology and End Results (SEER) registries with data from 2010-2017 to identify 49,654 patients diagnosed with de novo metastatic, stage IV CRC. We evaluated the pattern of bone, lung, liver and brain metastases by race and ethnicity. Using multi-variate logistic regression, we obtained adjusted odds ratios (aOR) to estimate the association between metastatic …

Background Early life adiposity and changes in adiposity over the life course are associated with mammographic breast density among postmenopausal women. However, the underlying mechanisms are unknown; therefore, we comprehensively examined the associations of early life body mass index (BMI) and changes in BMI from ages 10, 18 to age at mammogram with growth factor, RANK pathway, and sex hormone gene expression in 372 postmenopausal women. Methods We estimated early life BMI at age 10 using the validated 9‐level Stunkard pictogram. We calculated BMI at other ages (18, 30, and current age at mammogram) by dividing weight in kilograms at these ages with height in meters squared. Sequencing for gene expression was performed using the NanoString nCounter system. After adjusting for confounders, we estimated associations using multivariable linear regressions. Results A 10 …

Introduction: Racial/ethnic differences exist in early-stage breast cancer, but less is known about whether there are racial differences in metastatic sites of breast cancer. Thus, we examined racial/ethnic differences in metastatic behavior of de novo metastatic breast cancer (MBC). Methods: We identified 28,072 adult women (63.9% non-Hispanic White [NHW], 16.6% non-Hispanic Black [NHB], 7.7% non-Hispanic Asian or Pacific Islander [API], 11.8% Hispanic) diagnosed with de novo MBC in the Surveillance, Epidemiology and End Results between 2010 and 2018. Sites of distant metastasis included bone, lung, liver, and brain. Age-standardized incidence rates and incidence rate ratios (IRRs) were calculated. Logistic regressions were used to estimate the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: NHBs had the highest incidence of MBC (13.2 per 100,000). Bone is the …

Introduction: Changes in body mass index (BMI) over the life course are associated with both mammographic breast density and breast cancer risk in postmenopausal women. The underlying biological mechanisms driving these associations are, however, yet to be elucidated. Understanding these mechanisms could provide important insights into breast cancer prevention early in life. To provide insight into the biological mechanisms underlying the associations of BMI change over the life course and breast cancer risk in postmenopausal women, we comprehensively investigated the associations of BMI change from ages 10 and 18 to current age with gene expression of biomarkers that have previously been associated with breast cancer risk: growth factors (IGF1, IGFBP3, FGF1, FGF12, TGFB1), sex hormones (PRL, PGR, ESR1, STAT1, STAT5), and receptor activator of nuclear factor-κB (RANK) pathway (RANK …

An increasingly recognized mechanism of prostate cancer resistance is the transdifferentiation from adenocarcinoma to treatment-emergent neuroendocrine prostate cancer (t-NEPC), an extremely aggressive malignancy. The incidence of t-NEPC has been increasing in recent years, in part due to novel treatments that target the androgen receptor pathway. While clinicians historically had very few options for t-NEPC detection and treatment, recent research has uncovered key diagnostic tools and therapeutic targets that can be translated into improved patient care. In this article, we will outline the clinical features of t-NEPC and its molecular pathogenesis. Importantly, we will also discuss recently uncovered molecularly based strategies aimed at improving the diagnosis and treatment of t-NEPC. Finally, we will propose a unified algorithm that integrates clinical and molecular information for the clinical management …

Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through circulating progesterone are not clearly defined. We, therefore, investigated these associations in 364 premenopausal women with a median age of 44 years. We sequenced 179 progesterone receptor (PGR)-related single nucleotide polymorphisms (SNPs). We measured volumetric percent density (VPD) and non-dense volume (NDV) using Volpara. Linear regression models were fit on circulating progesterone or VPD/NDV separately. We performed mediation analysis to evaluate whether the effect of a SNP on VPD/NDV is mediated through circulating progesterone. All analyses were adjusted for confounders, phase of menstrual cycle and the Benjamini …

Background Black women living in southern states have the highest breast cancer mortality rate in the United States. The prognosis of de novo metastatic breast cancer is poor. Given these mortality rates, we are the first to link nationally representative data on breast cancer mortality hot spots (counties with high breast cancer mortality rates) with cancer mortality data in the United States and investigate the association of geographic breast cancer mortality hot spots with de novo metastatic breast cancer mortality among Black women. Methods We identified 7292 Black women diagnosed with de novo metastatic breast cancer in Surveillance, Epidemiology, and End Results (SEER). The county-level characteristics were obtained from 2014 County Health Rankings and linked to SEER. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) and 95 …

PurposeA dense breast on mammogram is a strong risk factor for breast cancer. Identifying factors that reduce mammographic breast density could thus provide insight into breast cancer prevention. Due to the limited number of studies and conflicting findings, we investigated the associations of medication use (specifically statins, aspirin, and ibuprofen) with mammographic breast density.MethodsWe evaluated these associations in 775 women who were recruited during an annual screening mammogram at Washington University School of Medicine, St. Louis. We measured mammographic breast density using Volpara. We used multivariable-adjusted linear regressions to determine the associations of medication use (statins, aspirin, and ibuprofen) with mammographic breast density. Least squared means were generated and back-transformed for easier interpretation.ResultsThe mean age of study participants …

ImportanceTo our knowledge, there is no consensus regarding differences in treatment and mortality between non-Hispanic African American and non-Hispanic White women with triple-negative breast cancer (TNBC). Little is known about whether racial disparities vary by sociodemographic, clinical, and neighborhood factors.ObjectiveTo examine the differences in clinical treatment and outcomes between African American and White women in a nationally representative cohort of patients with TNBC and further examine the contributions of sociodemographic, clinical, and neighborhood factors to TNBC outcome disparities.Design, Setting, and ParticipantsThis population-based, retrospective cohort study included 23 123 women who received a diagnosis of nonmetastatic TNBC between January 1, 2010, and December 31, 2015, followed up through December 31, 2016, and identified from the Surveillance …

572Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality …