Association of Imaging-Based Body Fat Distribution and Mammographic Density in the Multiethnic Cohort Adiposity Phenotype Study

Maskarinec, Gertraud; Ciba, Michelle; Ju, Dan; Shepherd, John; Ernst, Thomas; Wu, Anna H.; Monroe, Kristine R.; Lim, Unhee; Wilkens, Lynne R.; Marchand, Loı̈c Le

doi:10.1158/1055-9965.epi-19-1060

Cited by 3 publications

(1 citation statement)

References 42 publications

(58 reference statements)

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“…Recent large-scale studies of breast cancer patients found prognostic value in the presence of clinically non-evident muscle wasting detected with routine CT scans for staging, even in nonmetastatic patients and in a setting of changes of subcutaneous adipose tissue [18,19]. Other studies have investigated the prognostic value of body composition in association with metabolic risk factor profiles or adipokine levels, and found it added value to clinical decision making and showed a prognostic impact [20][21][22]. Thus, imaging appears to be able to contribute predictive information that might not otherwise be accessible.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients

Thaiss

Gatidis

Sartorius

et al. 2020

Cancer Immunol Immunother

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Background As cancer cachexia (CC) is associated with cancer progression, early identification would be beneficial. The aim of this study was to establish a workflow for automated MRI-based segmentation of visceral (VAT) and subcutaneous adipose tissue (SCAT) and lean tissue water (LTW) in a B16 melanoma animal model, monitor diseases progression and transfer the protocol to human melanoma patients for therapy assessment. Methods For in vivo monitoring of CC B16 melanoma-bearing and healthy mice underwent longitudinal three-point DIXON MRI (days 3, 12, 17 after subcutaneous tumor inoculation). In a prospective clinical study, 18 metastatic melanoma patients underwent MRI before, 2 and 12 weeks after onset of checkpoint inhibitor therapy (CIT; n = 16). We employed an in-house MATLAB script for automated whole-body segmentation for detection of VAT, SCAT and LTW. Results B16 mice exhibited a CC phenotype and developed a reduced VAT volume compared to baseline (B16 − 249.8 µl, − 25%; controls + 85.3 µl, + 10%, p = 0.003) and to healthy controls. LTW was increased in controls compared to melanoma mice. Five melanoma patients responded to CIT, 7 progressed, and 6 displayed a mixed response. Responding patients exhibited a very limited variability in VAT and SCAT in contrast to others. Interestingly, the LTW was decreased in CIT responding patients (− 3.02% ± 2.67%; p = 0.0034) but increased in patients with progressive disease (+ 1.97% ± 2.19%) and mixed response (+ 4.59% ± 3.71%). Conclusion MRI-based segmentation of fat and water contents adds essential additional information for monitoring the development of CC in mice and metastatic melanoma patients during CIT or other treatment approaches.

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Section: Introductionmentioning

confidence: 99%

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients

Thaiss

Gatidis

Sartorius

et al. 2020

Cancer Immunol Immunother

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Body Mass Index and Mammographic Density in a Multiracial and Multiethnic Population-Based Study

Barnard

Martheswaran

Meter

et al. 2022

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Mammographic density (MD) is strongly associated with breast cancer risk. We examined whether BMI partially explains racial and ethnic variation in MD. Methods: We used multivariable Poisson regression to estimate associations between BMI and binary MD (BI-RADS A&B versus BI-RADS C&D) among 160,804 women in the Utah mammography cohort. We estimated associations overall and within racial and ethnic subgroups and calculated population attributable risk percents (PAR%s). Results: We observed the lowest BMI and highest MD among Asian women, the highest BMI among Native Hawaiian and Pacific Islander women, and the lowest MD among American Indian and Alaska Native (AIAN) and Black women. BMI was inversely associated with MD (RRBMI>=30 v<25=0.43, 95% CI=0.42-0.44) in the full cohort, and estimates in all racial and ethnic subgroups were consistent with this strong inverse association. For women <45, although there was statistical evidence of heterogeneity in associations between BMI and MD by race and ethnicity (p=0.009), magnitudes of association were similar across groups. PAR%s for BMI and MD among women <45 were considerably higher in White women (PAR% 29.2, 95% CI=28.4-29.9) compared to all other groups with estimates ranging from PAR%Asain=17.2%, 95%CI=8.5-25.8 to PAR%Hispanic=21.5%, 95%CI=19.4-23.6. For women >=55, PAR%s for BMI and MD were highest among AIAN women (PAR% 37.5, 95% CI=28.1-46.9). Conclusions: While we observed substantial differences in the distributions of BMI and MD by race and ethnicity, associations between BMI and MD were generally similar across groups. Impact: Distributions of BMI and MD may be important contributors to breast cancer disparities.

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Body fatness and breast cancer risk in relation to phosphorylated mTOR expression in a sample of predominately Black women

et al. 2021

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Background The mechanistic target of rapamycin (mTOR) pathway promoted by positive energy imbalance and insulin-like growth factors can be a mechanism by which obesity influences breast cancer risk. We evaluated the associations of body fatness with the risk of breast cancer varied with phosphorylated (p)-mTOR protein expression, an indication of the pathway activation. Methods Women with newly diagnosed breast cancer (n = 715; 574 [80%] Black and 141 [20%] White) and non-cancer controls (n = 1983; 1280 [64%] Black and 713 [36%] White) were selected from the Women’s Circle of Health Study. Surgical tumor samples among the cases were immunostained for p-mTOR (Ser2448) and classified as p-mTOR-overexpressed, if the expression level ≥ 75th percentile, or p-mTOR-negative/low otherwise. Anthropometrics were measured by trained staff, and body composition was determined by bioelectrical impedance analysis. Odds ratios (ORs) of p-mTOR-overexpressed tumors and p-mTOR-negative/low tumors compared to controls were estimated using polytomous logistic regression. The differences in the associations by the p-mTOR expression status were assessed by tests for heterogeneity. Results Cases with p-mTOR-overexpressed tumors, but not cases with p-mTOR-negative/low tumors, compared to controls were more likely to have higher body mass index (BMI), percent body fat, and fat mass index (P-heterogeneity < 0.05), although the OR estimates were not significant. For the measurement of central adiposity, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 2.52, 95% CI = 1.46 to 4.34) and Q4 (OR = 1.99, 95% CI = 1.12 to 3.50) of waist circumference (WC) compared to controls. Similarly, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 1.82, 95% CI = 1.11 to 2.98) and Q4 (OR = 1.81, 95% CI = 1.11 to 2.98) of WHR compared to controls. These associations of WC and waist-to-hip ratio (WHR) did not differ by tumor p-mTOR status (P-heterogeneity = 0.27 and 0.48, respectively). Conclusions Our findings suggest that in this population composed of predominately Black women, body fatness is associated with breast cancer differently for p-mTOR overexpression and p-mTOR negative/low expression. Whether mTOR plays a role in the obesity and breast cancer association warrants confirmation by prospective studies.

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Association of Imaging-Based Body Fat Distribution and Mammographic Density in the Multiethnic Cohort Adiposity Phenotype Study

Cited by 3 publications

References 42 publications

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients

Body Mass Index and Mammographic Density in a Multiracial and Multiethnic Population-Based Study

Body fatness and breast cancer risk in relation to phosphorylated mTOR expression in a sample of predominately Black women

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