Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk

Height, adiposity and body fat distribution and breast density in young women

INTRODUCTION: Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. METHOD: Associations of height, adiposity and body fat distribution with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25-29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy x-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging (MRI). Associations were evaluated using linear mixed effects models. All tests of statistical significance are 2-sided. RESULTS: Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percent fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) each was associated significantly with a 44.4% - 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. However, after adjustment for childhood BMI only the DXA measures percent fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8% - 19.6% decrease in ADBV . In mutually adjusted analysis, percent fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in A:G ratio was associated with a 18.5% decrease in ADBV. CONCLUSIONS: Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations

Pubertal timing and breast density in young women: a prospective cohort study

Background Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. Methods From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. Results The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)). Conclusions Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk

Reconstruction tridimensionnelle d'objets. Application a la radiographie industrielle a partir d'un nombre tres limite de projections

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 78554 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

MRI enhancement in stromal tissue surrounding breast tumors: association with recurrence free survival following neoadjuvant chemotherapy.

RATIONALE AND OBJECTIVES: Normal-appearing stromal tissues surrounding breast tumors can harbor abnormalities that lead to increased risk of local recurrence. The objective of this study was to develop a new imaging methodology to characterize the signal patterns of stromal tissue and to investigate their association with recurrence-free survival following neoadjuvant chemotherapy. MATERIALS AND METHODS: Fifty patients with locally-advanced breast cancer were imaged with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before (V1) and after one cycle (V2) of adriamycin-cytoxan therapy. Contrast enhancement in normal-appearing stroma around the tumor was characterized by the mean percent enhancement (PE) and mean signal enhancement ratio (SER) in distance bands of 5 mm from the tumor edge. Global PE and SER were calculated by averaging all stromal bands 5 to 40 mm from tumor. Proximity-dependent PE and SER were analyzed using a linear mixed effects model and Cox proportional hazards model for recurrence-free survival. RESULTS: The mixed effects model displayed a decreasing radial trend in PE at both V1 and V2. An increasing trend was less pronounced in SER. Survival analysis showed that the hazard ratio estimates for each unit decrease in global SER was statistically significant at V1 [estimated hazard ratio = 0.058, 95% Wald CI (0.003, 1.01), likelihood ratio p = 0.03]; but was not so for V2. CONCLUSIONS: These findings show that stromal tissue outside the tumor can be quantitatively characterized by DCE-MRI, and suggest that stromal enhancement measurements may be further developed for use as a potential predictor of recurrence/disease-free survival following therapy

MRI enhancement in stromal tissue surrounding breast tumors: association with recurrence free survival following neoadjuvant chemotherapy.

Rationale and objectivesNormal-appearing stromal tissues surrounding breast tumors can harbor abnormalities that lead to increased risk of local recurrence. The objective of this study was to develop a new imaging methodology to characterize the signal patterns of stromal tissue and to investigate their association with recurrence-free survival following neoadjuvant chemotherapy.Materials and methodsFifty patients with locally-advanced breast cancer were imaged with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before (V1) and after one cycle (V2) of adriamycin-cytoxan therapy. Contrast enhancement in normal-appearing stroma around the tumor was characterized by the mean percent enhancement (PE) and mean signal enhancement ratio (SER) in distance bands of 5 mm from the tumor edge. Global PE and SER were calculated by averaging all stromal bands 5 to 40 mm from tumor. Proximity-dependent PE and SER were analyzed using a linear mixed effects model and Cox proportional hazards model for recurrence-free survival.ResultsThe mixed effects model displayed a decreasing radial trend in PE at both V1 and V2. An increasing trend was less pronounced in SER. Survival analysis showed that the hazard ratio estimates for each unit decrease in global SER was statistically significant at V1 [estimated hazard ratio = 0.058, 95% Wald CI (0.003, 1.01), likelihood ratio p = 0.03]; but was not so for V2.ConclusionsThese findings show that stromal tissue outside the tumor can be quantitatively characterized by DCE-MRI, and suggest that stromal enhancement measurements may be further developed for use as a potential predictor of recurrence/disease-free survival following therapy

Enhanced vertebra to disk ratio as a new semi-quantitative imaging biomarker for Gaucher disease patients

Purpose: Gaucher disease (GD) is an inherited lysosomal storage disorder. The Vertebral Disk Ratio (VDR) is a semi-quantitative imaging biomarker designed to diagnose and monitor GD. Computed from standard T1 MRI images, the VDR is derived from 2D segmentations. This study aimed to evaluate the 3D version of VDR, namely eVDR, and analyze the performances of two eVDR–derived response criteria for GD patients. Methods: Three datasets were used: 8 longitudinal GD patients, 13 non-GD patients, and 2 longitudinal GD patients with known Bone Marrow Burden (BMB) scores. Two eVDR-derived response criteria were tested: 1) a parametric version (PeVDR) averaging all eVDR measures recorded for the 5 lumbar vertebrae; and 2) a non-parametric version (NPeVDR), considering all eVDR measures as independent and evaluating therapeutic response in a paired fashion. Analyses included assessment of reader variability in eVDR (3D) versus VDR (2D) and comparison with BMB response criteria. Results: The repeatability of eVDR (3D) versus VDR (2D) demonstrated no difference in mean values but a lower variance (p < 0.004). The PeVDR intra-reader variability had a standard deviation < 0.1 with a coefficient of variation < 5%; the inter-reader variability featured a Limit of Agreement < 5% and a Bias < 3%. Observational comparison of eVDR and BMB scoring and sensitivity indicated a correlation between PeVDR and BMB, with an improved sensitivity with the NPeVDR version. Conclusions: Based on a standard MRI sequence, the eVDR imaging biomarker and its derived response criteria improved GD assessments and could help assessing other bone marrow diseases

Discrepancies of assessments in a RECIST 1.1 phase II clinical trial – association between adjudication rate and variability in images and tumors selection

Abstract Background In imaging-based clinical trials, it is common practice to perform double reads for each image, discrepant interpretations can result from these two different evaluations. In this study we analyzed discrepancies that occurred between local investigators (LI) and blinded independent central review (BICR) by comparing reader-selected imaging scans and lesions. Our goal was to identify the causes of discrepant declarations of progressive disease (PD) between LI and BICR in a clinical trial. Methods We retrospectively analyzed imaging data from a RECIST 1.1-based, multi-sites, phase II clinical trial of 179 patients with adult small cell lung cancer, treated with Cabazitaxel compared to Topotecan. Any discrepancies in the determination of PD between LI and BICR readers were reviewed by a third-party adjudicator. For each imaging time point and reader, we recorded the selected target lesions, non-target lesions, and new lesions. Odds ratios were calculated to measure the association between discrepant declarations of PD and the differences in reviewed imaging scans (e.g. same imaging modality but with different reconstruction parameters) and selected lesions. Reasons for discrepancies were analyzed. Results The average number of target lesions found by LI and BICR was respectively 2.9 and 3.4 per patient (p < 0.05), 18.4% of these target lesions were actually non-measurable. LI and BICR performed their evaluations based on different baseline imaging scans for 59% of the patients, they selected at least one different target lesion in 85% of patients. A total of 36.7% of patients required adjudication. Reasons of adjudication included differences in 1) reporting new lesions (53.7%), 2) the measured change of the tumor burden (18.5%), and 3) the progression of non-target lesions (11.2%). The rate of discrepancy was not associated with the selection of non-measurable target lesions or with the readers’ assessment of different images. Paradoxically, more discrepancies occurred when LI and BICR selected exactly the same target lesions at baseline compared to when readers selected not exactly the same lesions. Conclusions For a large proportion of evaluations, LI and BICR did not select the same imaging scans and target lesions but with a limited impact on the rate of discrepancy. The majority of discrepancies were explained by the difference in detecting new lesions. Trial Registration ARD12166 (https://clinicaltrials.gov/ct2/show/NCT01500720)

Intake of dietary carbohydrates in early adulthood and adolescence and breast density among young women

PurposeCarbohydrate&nbsp;intake increases postprandial insulin secretion and may affect breast density, a strong risk factor for breast cancer, early in life. We examined associations of adolescent and early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars with breast density among 182 young women.MethodsDiet was assessed using three 24-h recalls at each of five Dietary Intervention Study in Children (DISC) clinic visits when participants were age 10-19&nbsp;years and at the DISC06 Follow-Up Study clinic visit when participants were age 25-29&nbsp;years. Associations between energy-adjusted carbohydrates and MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at 25-29&nbsp;years were quantified using multivariable-adjusted mixed-effects linear models.ResultsAdolescent sucrose intakes and premenarcheal total carbohydrates intakes were modestly associated with higher %DBV (mean %DBVQ1 vs Q4, 16.6 vs 23.5% for sucrose; and 17.2 vs 22.3% for premenarcheal total carbohydrates, all Ptrend ≤ 0.02), but not with ADBV. However, adolescent intakes of fiber and fructose were not associated with %DBV and ADBV. Early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars were not associated with %DBV and ADBV.ConclusionsInsulinemic carbohydrate diet during puberty may be associated with adulthood breast density, but our findings need replication in larger studies. Clinical Trials Registration ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999