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Vascular density of histologically benign breast tissue from women with breast cancer: associations with tissue composition and tumor characteristics.

ABSTRACT: In breast tumors, it is well established that intratumoral angiogenesis is crucial for malignant progression, but little is known about the vascular characteristics of extratumoral, cancer-adjacent breast. Genome-wide transcriptional data suggest that extratumoral microenvironments may influence breast cancer phenotypes; thus, histologic features of cancer-adjacent tissue may also have clinical implications. To this end, we developed a digital algorithm to quantitate vascular density in approximately 300 histologically benign tissue specimens from breast cancer patients enrolled in the UNC Normal Breast Study (NBS). Specimens were stained for CD31, and vascular content was compared to demographic variables, tissue composition metrics, and tumor molecular features. We observed that the vascular density of cancer-adjacent breast was significantly higher in older and obese women, and was strongly associated with breast adipose tissue content. Consistent with observations that older and heavier women experience higher frequencies of ER+ disease, higher extratumoral vessel density was also significantly associated with positive prognostic tumor features such as lower stage, negative nodal status, and smaller size (<2 cm). These results reveal biological relationships between extratumoral vascular content and body size, breast tissue composition, and tumor characteristics, and suggest biological plausibility for the relationship between weight gain (and corresponding breast tissue changes) and breast cancer progression.

SUBMITTER: Fuller AM

PROVIDER: S-EPMC7029625 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Vascular density of histologically benign breast tissue from women with breast cancer: associations with tissue composition and tumor characteristics.

Fuller Ashley M AM Olsson Linnea T LT Midkiff Bentley R BR Kirk Erin L EL McNaughton Kirk K KK Calhoun Benjamin C BC Troester Melissa A MA

Human pathology 20190702

In breast tumors, it is well established that intratumoral angiogenesis is crucial for malignant progression, but little is known about the vascular characteristics of extratumoral, cancer-adjacent breast. Genome-wide transcriptional data suggest that extratumoral microenvironments may influence breast cancer phenotypes; thus, histologic features of cancer-adjacent tissue may also have clinical implications. To this end, we developed a digital algorithm to quantitate vascular density in approxim ...[more]

PMID: 31271812

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Project description:BackgroundWe investigated the associations of alcohol with percentage of epithelium, stroma, fibroglandular tissue (epithelium + stroma), and fat in benign breast biopsy samples.MethodsWe included 857 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII cohorts. Percentage of each tissue was measured on whole slide images using a deep-learning algorithm and then log-transformed. Alcohol consumption (recent and cumulative average) was assessed with semi-quantitative food frequency questionnaires. Regression estimates were adjusted for known breast cancer risk factors. All tests were 2-sided.ResultsAlcohol was inversely associated with % of stroma and fibroglandular tissue (recent ≥ 22 g/day vs. none: stroma: β = - 0.08, 95% Confidence Interval [CI] - 0.13; - 0.03; fibroglandular: β = - 0.08, 95% CI - 0.13; - 0.04; cumulative ≥ 22 g/day vs. none: stroma: β = - 0.08, 95% CI - 0.13; - 0.02; fibroglandular: β = - 0.09, 95% CI - 0.14; - 0.04) and positively associated with fat % (recent ≥ 22 g/day vs. none: β = 0.30, 95% CI 0.03; 0.57; cumulative ≥ 22 g/day vs. none: β = 0.32, 95% CI 0.04; 0.61). In stratified analysis, alcohol consumption was not associated with tissue measures in premenopausal women. In postmenopausal women, cumulative alcohol use was inversely associated with % of stroma and fibroglandular tissue and positively associated with fat % (≥ 22 g/day vs. none: stroma: β = - 0.16, 95% CI - 0.28; - 0.07; fibroglandular: β = - 0.18, 95% CI - 0.28; - 0.07; fat: β = 0.61, 95% CI 0.01; 1.22), with similar results for recent alcohol use.ConclusionOur findings suggest that alcohol consumption is associated with smaller % of stroma and fibroglandular tissue and a greater % of fat in postmenopausal women. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.

Project description:BackgroundWe investigated the associations of reproductive factors with the percentage of epithelium, stroma, and fat tissue in benign breast biopsy samples.MethodsThis 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.ResultsAs 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, the number of children was inversely associated with the percentage of stroma (β 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 (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.ConclusionsOur 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.

Dataset Information

Vascular density of histologically benign breast tissue from women with breast cancer: associations with tissue composition and tumor characteristics.

Publications

Vascular density of histologically benign breast tissue from women with breast cancer: associations with tissue composition and tumor characteristics.

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