A call for standardized reporting of early-onset colorectal peritoneal metastases.

BACKGROUND: The incidence of colorectal cancer (CRC) in patients under 50 years of age, i.e., early-onset CRC, has increased in the past two decades. Colorectal peritoneal metastases (CPM) will develop in 10-30% of CRC patients. CPM traditionally had a dismal prognosis, but surgery and novel systemic treatments appear to increase survival. Determining potential age-associated risk and prognostic factors is optimized when analyses use standardized age groupings. METHODS: We performed a review of early-onset CPM studies and compared variables used, e.g., age stratification and definitions of synchronous and metachronous CPM. We included studies published in PubMed up to November 2022 if results were stratified by age. RESULTS: Of 114 screened publications in English, only 10 retrospective studies met inclusion criteria. Incidence of CPM was higher in younger CRC patients (e.g. 23% vs. 2% for <25 vs. ≥25 years, P < 0.0001; and 57% vs. 39% vs. 4% for <20 vs. 20-25 vs. >25 years, P < 0.001); two studies reported higher proportion of younger African American CPM patients (e.g. 16% vs. 6% for <50 vs. ≥50 years). Studies used seven different age-stratification methods, presenting comparison challenges. CONCLUSION: Studies showed a higher proportion of CPM in younger patients, but directly comparing results was not possible due to inconsistent reporting. To better address this issue, CRC and CPM studies stratified by standard age groups (e.g. <50 vs. ≥50) are needed.

Electronic Nicotine Delivery Systems (ENDS) use Among Members of a Community Engagement Program.

Electronic nicotine delivery systems (ENDS) are relatively new and ENDS use data from community engagement programs may help us understand usage patterns and facilitate targeted longitudinal studies. Community members in Florida, USA, were asked about ENDS use, tobacco use, and health history/concerns by Community Health Workers. Among 7253 members recruited during 2014 to 2021 into our HealthStreet program, 1177 had ever used ENDS; the proportion increased from 12 to 27% from 2014 to 2021 (adjusted odds ratio (aOR) 2.5; 95% CI 1.7-3.5; Ever versus never used ENDS). Ever tobacco use was strongly associated with ENDS use; 69% of ever users were current tobacco users. Demographic determinants (sex, age, race) and food insecurity were strongest predictors of ENDS use. Most who had ever used ENDS were aged 18-25 (aOR 5.9; 95% CI 4.6-7.6; vs. aged 60 + years), White (aOR 3.7; 95% CI 3.2-4.3; vs. Black/African American), male (aOR 1.5; 95% CI 1.3-1.7; vs. female), and recently food insecure (aOR 1.8; 95% CI 1.5-2.0; vs. not recently food insecure). Those with respiratory issues were more likely to have used ENDS compared to those without (aOR 2.0; 95% CI 1.6-2.6; aOR 1.3; 95% CI 1.1-1.5). Members concerned about hypertension were less likely to have used ENDS (aOR 0.7; 95% CI 0.5-0.9). In this relatively rural, micropolitan sample, tobacco use, socio-economic determinants, and certain health history/concerns were strongly associated with ENDS use. Community outreach approaches are needed to further understand these factors and implement interventions.

Associations of established breast cancer risk factors with urinary estrogens in postmenopausal women.

PURPOSE: Circulating estrogens are an established risk factor for postmenopausal breast cancer (BCa). We describe the distribution of urinary estrogens, their metabolites, and relevant metabolic pathway ratios among healthy postmenopausal women and examine associations of several known BCa factors with these estrogen measures. METHODS: Eligible postmenopausal women (n = 167) had no history of hormone use (previous 6 months) and cancer/metabolic disorders and had a body mass index (BMI) ≤ 35 kg/m2. Estrogens were quantified in spot urine samples with liquid chromatography-high-resolution mass spectrometry and corrected for creatinine. We assessed overall distributions of estrogens and associations of age, BMI, race/ethnicity, parity/age at first birth, age at menarche, alcohol, and smoking with log-transformed estrogen measures using multivariate regression. RESULTS: BMI was positively associated with estrone (ß per unit = 0.04, 95% Confidence Interval [CI] 0.00; 0.07), combined parent estrogens (ß = 0.04, 95% CI 0.01; 0.07), and E2:total estrogens (ß = 0.04, 95% CI 0.02; 0.06), and inversely associated with 4-MeOE1 (ß = - 0.17, 95% CI - 0.33; - 0.02), E3:parent estrogens (ß = - 0.04, 95% CI - 0.07; - 0.00), and 16-pathway:parent (ß = - 0.04, 95% CI - 0.07; - 0.01). Being African American vs. white was associated with higher levels of 4-MeOE1 (ß = 3.41, 95% CI 0.74; 6.08), 17-epiE3 (ß = 1.19, 95% CI 0.07; 2.31), 2-pathway:parent (ß = 0.54, 95% CI 0.04; 1.04), and lower levels of E2:total estrogens (ß = - 0.48, 95% CI - 0.83; - 0.13). Having < 7 alcohol drinks/week vs. none was associated with higher levels of 16-ketoE2 (ß = 1.32, 95% CI 0.36; 2.27), 16-epiE3 (ß = 1.02, 95% CI 0.24; 1.79), and 17-epiE3 (ß = 0.55, 95% CI 0.02; 1.08). Smoking was positively associated with E3:parent (ß = 0.29, 95% CI 0.01; 0.57), 16-pathway:parent (ß = 0.25, 95% CI 0.01; 0.49), and inversely associated with estradiol (ß = - 0.52, 95% CI - 0.93; - 0.10). As compared to nulliparous, parous women with age at first birth ≥ 25 years had lower levels of estrone, combined parent estrogens, 2-OHE1, and 2-OHE2. CONCLUSION: Our findings suggest that BMI, race/ethnicity, and some reproductive and lifestyle factors may contribute to postmenopausal BCa through their effects on circulating estrogens.

Associations of reproductive breast cancer risk factors with breast tissue composition.

BACKGROUND: We investigated the associations of reproductive factors with the percentage of epithelium, stroma, and fat tissue in benign breast biopsy samples. METHODS: This study included 983 cancer-free women with biopsy-confirmed benign breast disease (BBD) within the Nurses' Health Study and Nurses' Health Study II cohorts. The percentage of each tissue type (epithelium, stroma, and fat) was measured on whole-section images with a deep-learning technique. All tissue measures were log-transformed in all the analyses to improve normality. The data on reproductive variables and other breast cancer risk factors were obtained from biennial questionnaires. Generalized linear regression was used to examine the associations of reproductive factors with the percentage of tissue types, while adjusting for known breast cancer risk factors. RESULTS: As compared to parous women, nulliparous women had a smaller percentage of epithelium (ß = - 0.26, 95% confidence interval [CI] - 0.41, - 0.11) and fat (ß = - 0.34, 95% CI - 0.54, - 0.13) and a greater percentage of stroma (ß = 0.04, 95% CI 0.01, 0.08). Among parous women, the number of children was inversely associated with the percentage of stroma (ß per child = - 0.01, 95% CI - 0.02, - 0.00). The duration of breastfeeding of ≥ 24 months was associated with a reduced proportion of fat (ß = - 0.30, 95% CI - 0.54, - 0.06; p-trend = 0.04). In a separate analysis restricted to premenopausal women, older age at first birth was associated with a greater proportion of epithelium and a smaller proportion of stroma. CONCLUSIONS: Our findings suggest that being nulliparous as well as having a fewer number of children (both positively associated with breast cancer risk) is associated with a smaller proportion of epithelium and a greater proportion of stroma, potentially suggesting the importance of epithelial-stromal interactions. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.

Early-Life and Adult Adiposity, Adult Height, and Benign Breast Tissue Composition.

BACKGROUND: Early-life and adult anthropometrics are associated with breast density and breast cancer risk. However, little is known about whether these factors also influence breast tissue composition beyond what is captured by breast density among women with benign breast disease (BBD). METHODS: This analysis included 788 controls from a nested case-control study of breast cancer within the Nurses' Health Study BBD subcohorts. Body fatness at ages 5 and 10 years was recalled using a 9-level pictogram. Weight at age 18, current weight, and height were reported via questionnaires. A deep-learning image analysis was used to quantify the percentages of epithelial, fibrous stromal, and adipose tissue areas within BBD slides. We performed linear mixed models to estimate beta coefficients (ß) and 95% confidence intervals (CI) for the relationships between anthropometrics and the log-transformed percentages of individual tissue type, adjusting for confounders. RESULTS: Childhood body fatness (level ≥ 4.5 vs. 1), BMI at age 18 (≥23 vs. <19 kg/m2), and current adult BMI (≥30 vs. <21 kg/m2) were associated with higher proportions of adipose tissue [ß (95% CI) = 0.34 (0.03, 0.65), 0.19 (-0.04-0.42), 0.40 (0.12, 0.68), respectively] and lower proportions of fibrous stromal tissue [-0.05 (-0.10, 0.002), -0.03 (-0.07, 0.003), -0.12 (-0.16, -0.07), respectively] during adulthood (all P trend < 0.04). BMI at age 18 was also inversely associated with epithelial tissue (P trend = 0.03). Adult height was not associated with any of the individual tissue types. CONCLUSIONS: Our data suggest that body fatness has long-term impacts on breast tissue composition. IMPACT: This study contributes to our understanding of the link between body fatness and breast cancer risk.See related commentary by Oskar et al., p. 590.