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 (β) 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 [β (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 Ptrend < 0.04). BMI at age 18 was also inversely associated with epithelial tissue (Ptrend = 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

1. Abstract /Summary: Discrepancies exist in the literature about the association of age and survival of patients with colorectal peritoneal metastases (CPM) who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We retrospectively analysed data from 811 patients with CPM aged 16 – 83 years, who were treated with CRS and HIPEC at the Peritoneal Malignancy Institute (PMI), UK, between 2000 and 2024. We ran repeated Cox proportional hazard (PH) and Kaplan-Meier survival analyses with preclinical covariates and peritoneal cancer index (PCI) covariates, to determine if associations of age with mortality hazard would be modified when the form of “age” was changed. More than 20 sets of analyses were run, each using a different form of age (continuous age, and age bins/groups e.g., <50 vs. ≥50 years). We found that within our population of pre-selected colorectal cancer patients, age at the time of CRS-HIPEC was not associated with mortality in any adjusted analyses. Early onset or late onset ages did not significantly affect survival once PCI score was included as a covariate. Discrepancies in age/survival associations reported in different studies may be due to lack of adjustment for important confounders. Our study suggests patients of any age with CPM, may benefit from CRS-HIPEC treatment.

Background We investigated the associations of reproductive factors with 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. 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 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 (β= -0.26, 95% confidence interval [CI] -0.41, -0.11) and fat (β= -0.34, 95% CI -0.54, -0.13) and a greater percentage of stroma (β = 0.04, 95% CI 0.01, 0.08). Among parous women, number of children was inversely associated with percentage of stroma (β per child= -0.01 (-0.02, -0.00). Duration of breastfeeding of ≥ 24 months was associated with a reduced proportion of fat (β= -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 reproductive factors with a protective effect on breast cancer risk may be associated with a greater proportion of epithelium and a smaller proportion of stroma, potentially suggesting importance of epithelial-stromal interactions. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.