Epidemiology of breast cancer among young black women and the rise in young-onset distant disease in the U.S.

Purpose: Rates of distant (stage IV) breast cancer have significantly increased since 1976 among young women 2cm. Conclusions: Among premenopausal black women, young age (<40 years) was associated with more aggressive breast tumor biology. Modifiable risk factors including breastfeeding, adiposity, and oral contraceptive use may be important targets for mitigating harms of young-onset breast cancer. In SEER, the frequency of aggressive disease decreased while imaging use dramatically increased from 1992-2011, suggesting that stage migration rather than shifting tumor biology has contributed to rising incidence of young-onset distant breast cancer.Doctor of Philosoph

Dietary Habits of Children 0-23 months in Rural Kansas: Early Life Diets of Rural Children

Introduction. Children in rural areas face increased rates of obesity compared to their urban counterparts, and diet in early childhood may influence the development of diseases related to food intake. This study sought to determine current diet of children 0-23 months of age in rural Kansas. Methods. Medical students participating in summer rural clinical experiences offered the survey to caregivers of children 0-23 months, born at term as singletons without a specialized diet. Recruitment occurred at appointments over 6 weeks in primary care offices. The survey was in the style of a validated Food Frequency Questionnaire for infants with an image for estimating portion sizes. Diets were compared to guidelines set by the Dietary Guidelines for Americans, 2020-2025. Results. Of 44 participants in the study, there were 21 children aged 0-5 months, 7 aged 6-11 months, and 16 aged 12-23 months. Breastfeeding rates were nearly double reported national averages. All children in the 0 to 5 month age group met guidelines. None of the children 6 to 11 months or 12 to 23 months met guidelines. In the 6 to 11 month group, 4 consumed food in addition to breastmilk or formula (complementary foods). In the 12-23 month group, protein and dairy foods were lower than, and whole grains and vegetables were higher than, reported national averages respectively. Conclusions. Children may fall short of dietary recommendations due to the amounts and types of food complementary to breast milk received in the diet

Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma

Complete age-related regression of mammary epithelium, often termed post-menopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study (NBS). High-resolution digital images of normal breast Hematoxylin & Eosin stained slides were partitioned into epithelium, adipose tissue, and non-fatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models Stromal area decreased (p=0.0002) and adipose tissue area increased (p<0.0001), with an approximate 0.7% change in area for each component, until age 55 when these area measures reached a steady state. While epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period

Temporal Trends in the Inflammatory Cytokine Profile of Human Breastmilk

A longer lifetime duration of breastfeeding may decrease the risk of breast cancer by reducing breast inflammation and mitigating inflammatory cytokine expression during postlactational involution. However, little is known about how the inflammatory cytokine profile in human breastmilk changes over time. To study temporal trends in breastmilk cytokine expression, we measured 80 human cytokines in the whey fraction of breastmilk samples from 15 mothers at 1, 4, 8, and 12 weeks postpartum. We used mixed models to identify temporal changes in cytokine expression and investigated parity status (multiparous vs. primiparous) as a potential confounder. Nine cytokines (monocyte chemoattractant protein-1, epithelial-derived neutrophil-activating protein-78, hepatocyte growth factor, insulin-like growth factor-binding protein-1, interleukin-16, interleukin-8, macrophage colony-stimulating factor, osteoprotegerin, and tissue inhibitor of metallopeptidase-2) had significantly decreased expression with increasing breastfeeding duration; all nine have known roles in breast involution, inflammation, and cancer and may serve as biomarkers of changing breast microenvironment. No cytokine significantly increased in level over the study period. Total protein concentration significantly decreased over time (p<0.0001), which may mediate the association between length of breastfeeding and inflammatory cytokine expression. Parity status did not confound temporal trends, but levels of several cytokines were significantly higher among multiparous versus primiparous women. Our results suggest that inflammatory cytokine expression during lactation is dynamic, and expressed milk may provide a noninvasive window into the extensive biological changes that occur in the postpartum breast

Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case-control study

Abstract Background Young-onset breast cancer (<40 years) is associated with worse prognosis and higher mortality. Breast cancer risk factors may contribute to distinct tumor biology and distinct age at onset, but understanding of these relationships has been hampered by limited representation of young women in epidemiologic studies and may be confounded by menopausal status. Methods We examined tumor characteristics and epidemiologic risk factors associated with premenopausal women’s and young women’s breast cancer in phases I–III of the Carolina Breast Cancer Study (5309 cases, 2022 control subjects). Unconditional logistic regression was used to assess heterogeneity by age (<40 vs. ≥40 years) and menopausal status. Results In both premenopausal and postmenopausal strata, younger women had more aggressive disease, including higher stage, hormone receptor-negative, disease as well as increased frequency of basal-like subtypes, lymph node positivity, and larger tumors. Higher waist-to-hip ratio was associated with reduced breast cancer risk among young women but with elevated risk among older women. Parity was associated with increased risk among young women and reduced risk among older women, while breastfeeding was more strongly protective for young women. Longer time since last birth was protective for older women but not for young women. In comparison, when we stratified by age, menopausal status was not associated with distinct risk factor or tumor characteristic profiles, except for progesterone receptor status, which was more commonly positive among premenopausal women. Conclusions Age is a key predictor of breast cancer biologic and etiologic heterogeneity and may be a stronger determinant of heterogeneity than menopausal status. Young women’s breast cancer appears to be etiologically and biologically distinct from that among older women

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy

Hyper-palatable foods in elementary school lunches: Availability and contributing factors in a national sample of US public schools.

BackgroundSchool cafeterias are a major point of influence for child nutrition. United States federal legislation requires the presence of important nutrients in school meals. However, legislation overlooks the potential presence of hyper-palatable foods in school lunches, a hypothesized factor that may influence children's eating behavior and obesity risk. The study sought to 1) quantify the prevalence of hyper-palatable foods (HPF) served in US elementary school lunches; and 2) determine whether food hyper-palatability varied based on school geographic region (East/Central/West), urbanicity (urban/micropolitan/rural), or meal item (entrée/side/fruit or vegetable).MethodsLunch menu data (N = 18 menus; N = 1160 total foods) were collected from a sample of six states that represented geographic regions of the United States (Eastern/Central/Western; Northern/Southern) and that had variability in urbanicity (urban, micropolitan, and rural) within each state. A standardized definition from Fazzino et al (2019) was used to identify HPF in lunch menus.ResultsHPF comprised almost half of foods in school lunches (M = 47%; SD = 5%). Compared to fruit/vegetable items, entrées were >23 times more likely to be hyper-palatable and side dishes were >13 times more likely to be hyper-palatable (p values .05). The majority of entrée and side items contained meat/meat alternatives and/or grains and likely aligned with the US federal reimbursable meal components of meat/meat alternatives and/or grains.Conclusions and implicationsHPF comprised almost half of foods offered in elementary school lunches. Entrées and side items were most likely to be hyper-palatable. US school lunches may be a key point of regular exposure to HPF among young children, a risk factor that may elevate child obesity risk. Public policy regulating HPF in school meals may be needed to protect children's health

Temporal Trends in the Inflammatory Cytokine Profile of Human Breastmilk

A longer lifetime duration of breastfeeding may decrease the risk of breast cancer by reducing breast inflammation and mitigating inflammatory cytokine expression during postlactational involution. However, little is known about how the inflammatory cytokine profile in human breastmilk changes over time. To study temporal trends in breastmilk cytokine expression, we measured 80 human cytokines in the whey fraction of breastmilk samples from 15 mothers at 1, 4, 8, and 12 weeks postpartum. We used mixed models to identify temporal changes in cytokine expression and investigated parity status (multiparous vs. primiparous) as a potential confounder. Nine cytokines (monocyte chemoattractant protein-1, epithelial-derived neutrophil-activating protein-78, hepatocyte growth factor, insulin-like growth factor-binding protein-1, interleukin-16, interleukin-8, macrophage colony-stimulating factor, osteoprotegerin, and tissue inhibitor of metallopeptidase-2) had significantly decreased expression with increasing breastfeeding duration; all nine have known roles in breast involution, inflammation, and cancer and may serve as biomarkers of changing breast microenvironment. No cytokine significantly increased in level over the study period. Total protein concentration significantly decreased over time (p<0.0001), which may mediate the association between length of breastfeeding and inflammatory cytokine expression. Parity status did not confound temporal trends, but levels of several cytokines were significantly higher among multiparous versus primiparous women. Our results suggest that inflammatory cytokine expression during lactation is dynamic, and expressed milk may provide a noninvasive window into the extensive biological changes that occur in the postpartum breast

Rotala mexicana Cham. et Schltdl.

原著和名: ミヅマツバ科名: ミソハギ科 = Lythraceae採集地: 群馬県 館林市 多々良沼付近 (上野 館林市 多々良沼付近)採集日: 1986/10/10採集者: 萩庭丈壽整理番号: JH024411国立科学博物館整理番号: TNS-VS-97441

Interactive multidisciplinary pilot workshop to improve medical student perception of and interest in breast surgical oncology

Background: Exposure to breast surgical oncology (BSO) and the multidisciplinary management of patients with breast cancer is limited in medical school. The purpose of this study was to assess changes in student perceptions of BSO as a career following an interactive multidisciplinary workshop. Methods: Pre-clinical medical students participated in a multidisciplinary, hands-on workshop, composed of breast radiology (BR), breast surgical oncology (BSO) and breast plastic reconstructive surgery (B-PRS). BR presented students screening and diagnostic breast imaging followed by hands-on ultrasound-guided biopsy on phantom simulators. BSO demonstrated lumpectomy, mastectomy, sentinel lymph node biopsy, and axillary lymph node dissections while B-PRS demonstrated oncoplastic techniques and autologous flap reconstruction with cadavers. Pre-and post-workshop surveys assessed student opinions on surgery and BSO. Results were compared using Wilcoxon Signed Rank, Wilcoxon Rank Sum, and Fisher's Exact. Results: The workshop was attended by twenty-four students. There was a statistically significant increase in interest in BSO from 52% to 86% after the workshop (p = 0.003). The event improved understanding of the work and lifestyle in BSO for 79% (19/24). All students (100%) expressed interest to further explore BSO. The most common attractors to a career in BSO were impacts on patients’ lives (N = 23), intellectual stimulation (N = 22), and earnings (N = 20). The most reported deterrents were lack of personal time (N = 18) and stress (N = 15). Conclusion: An interactive, anatomically based exposure to multidisciplinary breast cancer surgery improves medical student perception and interest in BSO. Medical schools should consider incorporating similar events to foster interest in BSO and other surgical subspecialties