How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis.

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 associated with an increased risk of breast cancer (odds ratio [OR] = 1.25; 95% CI = 1.07-1.48), when comparing the highest versus the lowest categories of weight gain. Menopausal status was a source of heterogeneity, with weight gain after age 18 associated with an increased risk of breast cancer in postmenopausal women (OR = 1.53; 95% CI = 1.40-1.68), but not in premenopausal women (OR = 1.01; 95% CI = 0.92-1.12). Additionally, a 5 kg increase in weight was positively associated with postmenopausal breast cancer risk (OR = 1.12; 95%CI = 1.05-1.21) in case-control studies. Findings from cohort studies were identical, with a positive association between weight gain after age 18 and breast cancer incidence in postmenopausal women (relative risk [RR] = 1.30; 95% CI = 1.09-1.36), but not in premenopausal women (RR = 1.06; 95% CI = 0.92-1.22). Weight gain after age 18 is a risk factor for postmenopausal breast cancer, highlighting the importance of weight control from early adulthood to reduce the incidence of postmenopausal breast cancer.

Design of filtering cable with defected conductor layer.

Electrical cables, often referred to as 'blood vessels' and 'nerves' of the industry, play a vital role in the connection of electrical devices. However, traditional cables that lack distributed filtering functions are usually the primary coupling path for electromagnetic compatibility (EMC) problems. An innovative design for a filtering cable, which incorporates insulated electrical wires coated with a specific defected conductor layer (DCL), enables it to achieve distributed filtering advantages along its axis. Microwave network analysis is employed to build the two-port network model of filtering cable, which efficiently analyzes the cascading characteristics of periodic or aperiodic filtering cables. To validate, the flexible printed circuit board (FPCB) with sawtooth dumbbell-shaped DCL and mounted by capacitors is wrapped around the stripped section of the coaxial cable to manufacture a multi-stopband filtering cable. Simulated and measured results demonstrate that the proposed filtering cable can be effectively suppressed in the stopband, which can be adjusted by changing the values of capacitors.

Breast Cancer Incidence Among US Women Aged 20 to 49 Years by Race, Stage, and Hormone Receptor Status.

Importance: Breast 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. Objective: To 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 Participants: This 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 Measures: Age-standardized incidence rates (ASIR), incidence rate ratios (IRR), and average annual percent changes (AAPC) stratified by race and ethnicity, hormone receptor status, tumor stage, and age at diagnosis. Results: Out of 217 815 eligible women (1485 American Indian or Alaska Native [0.7%], 25 210 Asian or Pacific Islander [11.6%], 27 112 non-Hispanic Black [12.4%], 37 048 Hispanic [17.0%], 126 960 non-Hispanic White [58.3%]), the majority were diagnosed with an ER+/PR+ tumor (134 024 [61.5%]) and were diagnosed with a stage I tumor (81 793 [37.6%]). Overall, invasive breast cancer incidence increased (AAPC, 0.79; 95% CI, 0.42 to 1.15), with increasing trends across almost all racial and ethnic groups. ASIR increased for ER+/PR+ (AAPC, 2.72; 95% CI, 2.34 to 3.12) and ER+/PR- tumors (AAPC, 1.43; 95% CI, 1.00 to 1.87), and decreased for ER-/PR+ (AAPC, -3.25; 95% CI, -4.41 to -2.07) and ER-/PR- tumors (AAPC, -0.55; 95% CI, -1.68 to 0.60). For women aged 20 to 29 and 30 to 39 years, ASIRs were highest among non-Hispanic Black women (age 20-29 years: IRR, 1.53; 95% CI, 1.43 to 1.65; age 30-39 years: IRR, 1.15; 95% CI, 1.12 to 1.18). For women aged 40 to 49 years, ASIR was lower for non-Hispanic Black women (IRR, 0.96; 95% CI, 0.94 to 0.97) compared with non-Hispanic White women. Incidence rates increased for stages I and IV tumors but decreased for stage II and III tumors. Age-period-cohort analysis demonstrated both cohort and period effects on breast cancer incidence (P < .001). Conclusions and Relevance: In this population-based cross-sectional analysis, an increase in breast cancer incidence rates among young US women and age-related crossover between non-Hispanic White and Black women were observed. Prevention efforts in young women need to adopt a targeted approach to address racial disparities in incidence rates observed at different age phases.

The impact of marital status on tumor aggressiveness, treatment, and screening among black and white men diagnosed with prostate cancer.

PURPOSE: To examine the association of marital status with prostate cancer outcomes in a racially-diverse cohort. METHODS: The 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 with prostate cancer. RESULTS: Black men were less likely to be married than White men (68.1% vs. 83.6%). Not being married (vs. married) was associated with increased odds of high-aggressive tumors in the overall study population (adjusted Odds Ratio (aOR): 1.56; 95% Confidence Interval (CI): 1.20-2.02) and both Black and White men in race-stratified analyses. Unmarried men were less likely to receive definitive treatment in the overall study population (aOR: 0.68; 95% CI: 0.54-0.85). In race-stratified analyses, unmarried Black men were less likely to receive definitive treatment. Both unmarried Black and White men were less likely to have a history of prostate cancer screening than married men. CONCLUSION: Lower rates of marriage among Black men might signal decreased support for treatment decision-making, symptom management, and caregiver support which could potentially contribute to prostate cancer disparities.

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD. With major advances in molecular technology, including the emergence of gene-editing techniques, along with deep whole-genome sequencing and high-throughput array-based genotyping, scientists now have the opportunity to not only discover genomic mechanisms underlying CVD but use this knowledge for the life-course prevention and treatment of these conditions. The current review focuses on innovations in the field of genomics and their applications to monogenic and polygenic CVD prevention and treatment. With respect to monogenic CVD, we discuss how the emergence of whole-genome sequencing technology has accelerated the discovery of disease-causing variants, allowing comprehensive screening and early, aggressive CVD mitigation strategies in patients and their families. We further describe advances in gene editing technology, which might soon make possible cures for CVD conditions once thought untreatable. In relation to polygenic CVD, we focus on recent innovations that leverage findings of genome-wide association studies to identify druggable gene targets and develop predictive genomic models of disease, which are already facilitating breakthroughs in the life-course treatment and prevention of CVD. Gaps in current research and future directions of genomics studies are also discussed. In aggregate, we hope to underline the value of leveraging genomics and broader multiomics information for characterizing CVD conditions, work which promises to expand precision approaches for the life-course prevention and treatment of CVD.

The Role of BMI in Allostatic Load and Risk of Cancer Death.

INTRODUCTION: Obesity 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. METHODS: A 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). RESULTS: In 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 risk of cancer death (adjusted subdistribution hazard ratio=1.03; 95% CI=0.78, 1.34) among underweight/healthy weight adults, a 31% increased risk of cancer death (adjusted subdistribution hazard ratio=1.31; 95% CI=1.02, 1.67) among overweight adults, and a 39% increased risk of death (adjusted subdistribution hazard ratio=1.39; 95% CI=1.04, 1.88) among obese adults, when compared to those with low allostatic load. CONCLUSIONS: The risk of cancer death is highest among those with high allostatic load and obese BMI, but this effect was attenuated among those with high allostatic load and underweight/healthy or overweight BMI.

Exploring the intersectionality of race/ethnicity with rurality on breast cancer outcomes: SEER analysis, 2000-2016.

PURPOSE: Disparities 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. METHODS: We 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. RESULTS: Compared with non-Hispanic white-urban (NH-white-U) women, NH-black-U, NH-black-rural (R), Hispanic-U, and Hispanic-R women, respectively, were at increased odds of no receipt of surgical treatment (NH-black-U, AOR = 1.98, 95% CI 1.91-2.05; NH-black-R, AOR = 1.72, 95% CI 1.52-1.94; Hispanic-U, AOR = 1.58, 95% CI 1.52-1.65; and Hispanic-R, AOR = 1.40, 95% CI 1.18-1.67), late-stage diagnosis (NH-black-U, AOR = 1.32, 95% CI 1.29-1.34; NH-black-R, AOR = 1.29, 95% CI 1.22-1.36; Hispanic-U, AOR = 1.25, 95% CI 1.23-1.27; and Hispanic-R, AOR = 1.17, 95% CI 1.08-1.27), and increased risks for breast cancer death (NH-black-U, AHR = 1.46, 95% CI 1.43-1.50; NH-black-R, AHR = 1.42, 95% CI 1.32-1.53; and Hispanic-U, AHR = 1.10, 95% CI 1.07-1.13). CONCLUSION: Regardless of rurality, NH-black and Hispanic women had significantly increased odds of late-stage diagnosis, no receipt of treatment, and risk of breast cancer death.

Racial and Ethnic Differences in Rural-Urban Trends in 5-Year Survival of Patients With Lung, Prostate, Breast, and Colorectal Cancers: 1975-2011 Surveillance, Epidemiology, and End Results (SEER).

Importance: Considering 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. Objective: To 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 Participants: This 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 Measures: The 5-year cancer-specific survival probability of urban and rural patients for each cancer type was estimated by fitting Cox proportional hazard regression models accounting for race, ethnicity, tumor characteristics, and other sociodemographic characteristics. A generalized linear regression model was used to estimate the mean estimated probability of survival for each stratum. Joinpoint regression analysis estimated periods of significant change in survival. Results: In this study, data from 3 659 417 patients with cancer (median [IQR] age, 67 [58-76]; 1 918 609 [52.4%] male; 237 815 [6.5%] Hispanic patients; 396 790 [10.8%] Black patients; 2 825 037 [77.2%] White patients) were analyzed, including 888 338 patients with lung cancer (24.3%), 750 704 patients with colorectal cancer (20.5%), 987 826 patients with breast cancer (27.0%) breast, and 1 023 549 patients with prostate cancer (28.0%). There were 430 353 rural patients (11.8%). Overall, there was an equal representation of rural and urban men. Rural patients were likely to be non-Hispanic White individuals, have more cases of distant tumors, and be older. Rural and non-Hispanic Black patients for all cancer types often had shorter survival. From 1975 to 2016, the 5-year lung cancer survival rate was shorter for non-Hispanic Black rural patients in 1975 at 48%, while increasing to 57% for both non-Hispanic Black urban and rural patients in 2011, but still the shortest among all cancer types. In 1975, the longest survival rate was observed in urban Asian and Pacific Islander patients with breast cancer at 86%, and in 2011, the longest survival rate was observed in urban non-Hispanic White patients with XX cancer at 92%. Conclusions and Relevance: Even after accounting for sociodemographic and tumor characteristics, these findings suggest that non-Hispanic Black patients with cancer are particularly vulnerable to cancer burden, and resources are urgently needed to reverse decades-old survival trends.

Changes in adiposity over the life course and gene expression in postmenopausal women.

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 kg/m2 increase in early life BMI at age 10 was associated with a 17.2% decrease in RANKL gene expression (95% confidence interval [CI] = -30.8, -0.9) but was not associated with changes in other markers. BMI changes from ages 10, 18 to age at mammogram were associated with an increase in BMP2 and decreases in RANK, RANKL, and TNFRSF13B gene expression but were not associated with gene expression of other markers. A 10 kg/m2 increase in early life BMI from age 10 to current age was associated with a 7.8% increase in BMP2 (95% CI = -1.4, 17.8), an 8.5% decrease in RANK (95% CI = -13.9, -2.8), a 10.4% decrease in RANKL (95% CI = -16.9, -3.3), and an 8.5% decrease in TNFRSF13B gene expression (95% CI = -13.8, -2.8). CONCLUSION: The results provide new insights into the biological mechanisms underlying the associations of adiposity changes from early life to adulthood and early life adiposity with mammographic breast density in postmenopausal women.

Family History of Breast Cancer and Mammographic Breast Density in Premenopausal Women.

Importance: Family 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. Objectives: To investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements. Design, Setting, and Participants: This 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. Exposures: Family history of breast cancer (FHBC). Main Outcomes and Measures: The primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set). Multivariable regressions were performed using a log-transformed normal distribution for the discovery set and a logistic distribution for the validation set. Results: Of 14 415 premenopausal women included in the study, the discovery set and validation set had similar characteristics (discovery set with FHBC: mean [SD] age, 47.1 [5.6] years; 15 [17.2%] were Black or African American women and 64 [73.6%] were non-Hispanic White women; discovery set with no FHBC: mean [SD] age, 47.7 [4.5] years; 87 [31.6%] were Black or African American women and 178 [64.7%] were non-Hispanic White women; validation set with FHBC: mean [SD] age, 46.8 [7.3] years; 720 [33.4%] were Black or African American women and 1378 [64.0%] were non-Hispanic White women]; validation set with no FHBC: mean [SD] age, 47.5 [6.1] years; 4572 [38.5%] were Black or African American women and 6632 [55.8%] were non-Hispanic White women]). In the discovery set, participants who had FHBC were more likely to have a higher mean volumetric percent density compared with participants with no FHBC (11.1% vs 9.0%). In the multivariable-adjusted model, volumetric percent density was 25% higher (odds ratio [OR], 1.25 ;95% CI, 1.12-1.41) in women with FHBC compared with women without FHBC; and 24% higher (OR, 1.24; 95% CI, 1.10-1.40) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.40; 95% CI, 0.95-2.07) compared with women with no relatives affected. In the validation set, women with a positive FHBC were more likely to have dense breasts (BI-RADS 3-4) compared with women with no FHBC (BI-RADS 3: 41.1% vs 38.8%; BI-RADS 4: 10.5% vs 7.7%). In the multivariable-adjusted model, the odds of having dense breasts (BI-RADS 3-4) were 30% higher (OR, 1.30; 95% CI, 1.17-1.45) in women with FHBC compared with women without FHBC; and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.38; 95% CI, 0.85-2.23) compared with women with no relatives affected. Conclusions and Relevance: In this cohort study, having an FHBC was positively associated with mammographic breast density in premenopausal women. Our findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer.

Gastric Organoids: Progress and Remaining Challenges.

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 limitations of these models and look to the future to present potential ways gastric organoids will advance treatment options for patients with GC.

Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?

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-Hochberg false discovery (FDR) adjusted p-value was applied to correct for multiple testing. In multivariable analyses, only PGR rs657516 had a direct effect on VPD (averaged direct effect estimate = - 0.20, 95%CI = - 0.38 ~ - 0.04, p-value = 0.02) but this was not statistically significant after FDR correction and the effect was not mediated by circulating progesterone (mediation effect averaged across the two genotypes = 0.01, 95%CI = - 0.02 ~ 0.03, p-value = 0.70). Five SNPs (PGR rs11571241, rs11571239, rs1824128, rs11571150, PGRMC1 rs41294894) were associated with circulating progesterone but these were not statistically significant after FDR correction. SNPs in PGR-related genes were not associated with VPD, NDV and circulating progesterone did not mediate the associations, suggesting that the effects, if any, of these SNPs on MD are independent of circulating progesterone. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-021-00438-1.

Medication use and mammographic breast density.

PURPOSE: A 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. METHODS: We 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. RESULTS: The mean age of study participants was 52.9 years. Statin use in the prior 12 months was not associated with volumetric percent density or dense volume, but was positively associated with non-dense volume. The mean volumetric percent density was 8.6% among statin non-users, 7.2% among women who used statins 1-3 days/week, and 7.3% among women who used statins ≥ 4 days/week (p trend = 0.07). The non-dense volume was 1297.1 cm3 among statin non-users, 1368.7 cm3 among women who used statins 1-3 days/week, and 1408.4 cm3 among those who used statins ≥ 4 days/week (p trend = 0.02). We did not observe statistically significant differences in mammographic breast density by aspirin or ibuprofen use. CONCLUSION: Statin, aspirin, and ibuprofen use was not associated with volumetric percent density and dense volume, but statin use was positively associated with non-dense volume. Any potential associations of these medications with breast cancer risk are unlikely to be mediated through an effect on volumetric percent density.

Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women With Triple-Negative Breast Cancer.

IMPORTANCE: To 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. OBJECTIVE: To 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 PARTICIPANTS: This 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, Epidemiology, and End Results data set. The study was conducted from July 2019 to November 2020. The analyses were performed from July 2019 to June 2020. EXPOSURES: Race and ethnicity, including non-Hispanic African American and non-Hispanic White race. MAIN OUTCOMES AND MEASURES: Using logistic regression analysis and competing risk regression analysis, we estimated odds ratios (ORs) of receipt of treatment and hazard ratios (HRs) of breast cancer mortality in African American patients compared with White patients. RESULTS: Of 23 213 participants, 5881 (25.3%) were African American women and 17 332 (74.7%) were White women. Compared with White patients, African American patients had lower odds of receiving surgery (OR, 0.69; 95% CI, 0.60-0.79) and chemotherapy (OR, 0.89; 95% CI, 0.81-0.99) after adjustment for sociodemographic, clinicopathologic, and county-level factors. During a 43-month follow-up, 3276 patients (14.2%) died of breast cancer. The HR of breast cancer mortality was 1.28 (95% CI, 1.18-1.38) for African American individuals after adjustment for sociodemographic and county-level factors. Further adjustment for clinicopathological and treatment factors reduced the HR to 1.16 (95% CI, 1.06-1.25). This association was observed in patients living in socioeconomically less deprived counties (HR, 1.26; 95% CI, 1.14-1.39), urban patients (HR, 1.21; 95% CI, 1.11-1.32), patients having stage II (HR, 1.19; 95% CI, 1.02-1.39) or III (HR, 1.15; 95% CI, 1.01-1.31) tumors that were treated with chemotherapy, and patients younger than 65 years (HR, 1.24; 95% CI, 1.12-1.37). CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, African American women with nonmetastatic TNBC had a significantly higher risk of breast cancer mortality compared with their White counterparts, which was partially explained by their disparities in receipt of surgery and chemotherapy.

Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance.

Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species.

Breast Cancer Mortality Hot Spots Among Black Women With de Novo Metastatic Breast Cancer.

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% confidence intervals (CIs) for mortality between hot spot and non-hot spot counties. Results: Among 7292 patients, 393 (5.4%) resided in breast cancer mortality hot spots. Women residing in hot spots had similar risks of breast cancer-specific mortality (aHR = 0.99, 95% CI = 0.85 to 1.15) and all-cause mortality (aHR = 0.97, 95% CI = 0.84 to 1.11) as women in non-hot spots after adjusting for individual and tumor-level factors and treatments. Additional adjustment for county-level characteristics did not impact mortality. Conclusion: Living in a breast cancer mortality hot spot was not associated with de novo metastatic breast cancer mortality among Black women. Future research should begin to examine variation in both individual and population-level determinants, as well as in molecular and genetic determinants that underlie the aggressive nature of de novo metastatic breast cancer.

Racial and ethnic disparities in 21-gene recurrence scores, chemotherapy, and survival among women with hormone receptor-positive, node-negative breast cancer.

PURPOSE: Cutoffs of the 21-gene recurrence score (RS), a commonly used genomic assay for hormone receptor-positive breast cancer, have been updated. Little is known about racial/ethnic differences in RS results, RS-guided chemotherapy use, and outcomes on updated cutoff (RS ≥ 31 defined as high-risk) in the real-world setting. METHODS: A total of 81,937 women [75.0% whites, 7.7% blacks, 8.3% Asian American/Pacific Islanders (AAPIs), and 9.0% Hispanics] diagnosed with hormone receptor-positive breast cancer between 2004 and 2015, who received the 21-gene assay, were identified from the Surveillance, Epidemiology, and End Results. Logistic regressions estimated the race-associated odds ratios (ORs) of RS and chemotherapy use. Cox regressions estimated the race-associated hazard ratios (HRs) of breast cancer-specific and all-cause mortality. RESULTS: Compared with white women, black women were more likely to have RS-defined high-risk tumors (adjusted OR [aOR] 1.29; 95% CI 1.16-1.42). In high RS, blacks had lower odds of chemotherapy use (aOR 0.76; 95% CI 0.62-0.94) than whites, particularly among women ≥ 65 years (aOR 0.51; 95% CI 0.35-0.76), while AAPI and Hispanic women had no variation in chemotherapy use compared with whites in high RS. Black women had a higher risk of breast cancer-specific mortality (HR 1.37; 95% CI 1.12-1.67) and all-cause mortality compared with white women after adjusting for demographic and pathological factors, county-level socioeconomic deprivation, treatments and RS; AAPIs had lower mortality and Hispanics had similar mortality. CONCLUSIONS: Black women were more likely to have a high-risk RS tumor and less likely to receive chemotherapy in the group of high RS, especially those ≥ 65 years. Further studies are needed to identify barriers to chemotherapy in black patients with high RS scores.

A Comparative Analysis of Online Medical Record Utilization and Perception by Cancer Survivorship.

BACKGROUND: Cancer survivors face many challenges including coordinating care across multiple providers and maintaining medical records from multiple institutions. Access and utilization of online medical records could help cancer survivors manage this complexity. Here, we examined how cancer survivors differ from those without a history of cancer with regards to utilization and perception of medical records. METHODS: We conducted a cross-sectional study of 3491 respondents, from the Health Information National Trends survey 5, cycle 2. The association of medical record utilization and perceptions with cancer survivorship was assessed using survey-weighted logistic regression. RESULTS: Cancer survivors (n=593) were more likely to report that a provider maintains a computerized medical record [adjusted odds ratio (AOR)=2.05; 95% confidence (CI), 1.24-3.41] and were more likely to report confidence in medical record safeguards (AOR=1.44; 95% CI, 1.03-2.03). However, cancer survivors were no more likely to access online medical records than those without a history of cancer (AOR=1.13; 95% CI, 0.69-1.86). Cancer survivors were no more likely to report privacy concerns as a reason for not accessing online medical records, however, survivors were more likely to report a preference for speaking directly with a provider as a reason for not accessing online medical records (AOR=2.24; 95% CI, 0.99-5.05). CONCLUSIONS: Although cancer survivors are more likely to trust medical record safe guards and do not express increased concerns about online medical record privacy, a preference to speak directly with provider is a barrier of use.

Determinants of Mammographic Breast Density by Race Among a Large Screening Population.

BACKGROUND: Because of the mixed reports from smaller studies, we examined associations of race with mammographic breast density and evaluated racial differences in the determinants of breast density. METHODS: Participants included 37 839 women (23 166 non-Hispanic white and 14 673 African American) receiving screening mammograms at the Joanne Knight Breast Health Center at Washington University School of Medicine from June 2010 to December 2015. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System (5th edition). To determine the association of race and participant characteristics with mammographic breast density, we used multivariable polytomous logistic regression models (reference group: almost entirely fatty). RESULTS: African American women had increased odds of extremely dense (adjusted odds ratio = 1.31, 95% confidence interval = 1.13 to 1.52) and reduced odds of heterogeneously dense breasts (adjusted odds ratio = 0.91, 95% confidence interval = 0.84 to 0.99) compared with non-Hispanic white women. Altogether, race, parity and age at first birth, current age, current body mass index (BMI), BMI at age 18 years, menarche, family history of breast cancer, oral contraceptive use, alcohol use, and menopausal status explained 33% of the variation in mammographic breast density. Among African American and non-Hispanic white women, these factors explained nearly 28.6% and 33.6% of the variation in mammographic density, respectively. Current BMI provided the greatest explanation of breast density (26.2% overall, 22.2% in African American, and 26.2% in non-Hispanic white women). CONCLUSIONS: The determinants of mammographic breast density were generally similar between African American women and non-Hispanic white women. After adjustments for confounders, African Americans had higher likelihood of extremely dense breasts but lower likelihood of heterogeneously dense breasts. The greatest explanation of breast density was provided by BMI, regardless of race.

Regular Coffee Consumption Is Associated with Lower Regional Adiposity Measured by DXA among US Women.

BACKGROUND: Coffee is among the most popular daily beverages in the United States. Importantly, coffee consumption has been associated with a lower risk of multiple health outcomes including a reduction in adiposity. DXA is a means to assess body fat and distribution. OBJECTIVES: The aim of this study was to examine the relation between coffee consumption and DXA-assessed adiposity and adiposity distribution. METHODS: Cross-sectional data from the NHANES were used. Participants were adults aged 20-69 y from the 2003-2004 and 2005-2006 waves. Information on coffee consumption was assessed through the FFQ (categorized as no coffee, 0 to <0.25 cup/d, 0.25 to <1 cup/d, 1 cup/d, 2-3 cups/d, or ≥4 cups/d). Both caffeinated and decaffeinated coffee consumption were included. Trunk fat and total fat percentage were measured via whole-body DXA scans. The association between coffee consumption and body fat was investigated using age-adjusted and multivariable-adjusted linear regression models which accounted for sample weights. RESULTS: Higher coffee consumption was associated with significantly lower total body fat percentage and trunk body fat percentage in a dose-response manner (all P values < 0.05) among women. Although this dose-response relation was nonsignificant among men, men aged 20-44 y who drank 2-3 cups/d had 1.3% (95% CI: -2.7%, 0.1%) less total fat and 1.8% (95% CI: -3.3%, -0.4%) less trunk fat than those who did not consume coffee. Furthermore, the association between coffee consumption and body fat percentage exhibited for both caffeinated and decaffeinated coffee among women (all P for trend < 0.001) but not among men (all P for trend > 0.05). CONCLUSIONS: The present study found a significant association between higher coffee consumption and lower DXA-measured adiposity. Moreover, a gender difference in this association in the general US adult population was also observed.