Dataset Information

Postlactational involution biomarkers plasminogen and phospho-STAT3 are linked with active age-related lobular involution.

ABSTRACT:

Purpose

Breast terminal duct lobular units undergo two distinctive physiological processes of involution: age-related lobular involution (LI), which is gradual and associated with decreased breast cancer risk, and postlactational involution, which is relatively precipitous, occurs with weaning, and has been associated with potentiation of tumor aggressiveness in animal models. Here we assessed whether markers of postlactational involution are associated with ongoing LI in a retrospective tissue cohort.

Methods

We selected 57 women from the Mayo Clinic Benign Breast Disease Cohort who underwent multiple biopsies and who were average age 48 at initial biopsy. Women were classified as having progressive or non-progressive LI between initial and subsequent biopsy. Serial tissue sections were immunostained for plasminogen, matrix metalloproteinase 9 (MMP-9), phospho-STAT3 (pSTAT3), tenascin C, Ki67, CD44, cytokeratin 14 (CK14), cytokeratin 19 (CK19), and c-myc. All but Ki67 were digitally quantified. Associations between maximal marker expression per sample and progressive versus non-progressive LI were assessed using logistic regression and adjusted for potential confounders.

Results

While no biomarker showed statistically significant association with LI progression when evaluated individually, lower expression of pSTAT3 (OR 0.35, 95% CI 0.13-0.82, p = 0.01) and higher expression of plasminogen (OR 2.89, 95% CI 1.14-8.81, p = 0.02) were associated with progressive LI in models simultaneously adjusted for all biomarkers. Sensitivity analyses indicated that the strengthening in association for pSTAT3 and plasminogen with progressive LI was due to collinearity between these two markers.

Conclusions

This is the first study to identify biomarkers of active LI. Our findings that plasminogen and pSTAT3 are significantly associated with LI suggest that they may represent signaling nodes or biomarkers of pathways common to the processes of postlactational involution and LI.

SUBMITTER: Stallings-Mann ML

PROVIDER: S-EPMC5645446 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Postlactational involution biomarkers plasminogen and phospho-STAT3 are linked with active age-related lobular involution.

Stallings-Mann Melody L ML Heinzen Ethan P EP Vierkant Robert A RA Winham Stacey J SJ Hoskin Tanya L TL Denison Lori A LA Nassar Aziza A Hartmann Lynn C LC Visscher Daniel W DW Frost Marlene H MH Sherman Mark E ME Degnim Amy C AC Radisky Derek C DC

Breast cancer research and treatment 20170727 1

<h4>Purpose</h4>Breast terminal duct lobular units undergo two distinctive physiological processes of involution: age-related lobular involution (LI), which is gradual and associated with decreased breast cancer risk, and postlactational involution, which is relatively precipitous, occurs with weaning, and has been associated with potentiation of tumor aggressiveness in animal models. Here we assessed whether markers of postlactational involution are associated with ongoing LI in a retrospective ...[more]

PMID: 28752190

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Project description:BackgroundExposure to certain outdoor air pollutants may be associated with a higher risk of breast cancer, though potential underlying mechanisms are poorly understood. We examined whether outdoor air pollution was associated with involution of terminal duct lobular units (TDLUs), the histologic site where most cancers arise and an intermediate marker of breast cancer risk.MethodsPathologist-enumerated TDLUs were assessed in H&E (hematoxylin and eosin)-stained breast tissue sections from 1904 US women ages 18-75 who donated to the Susan G. Komen Tissue Bank (2009-2012). The 2009 annual fine particulate matter < 2.5 μm in diameter (PM2.5) total mass (μg/m3) at each woman's residential address was estimated from the Environmental Protection Agency's Downscaler Model combining Community Multiscale Air Quality (CMAQ) System modeling with air quality monitoring data. We secondarily considered CMAQ-modeled components of PM2.5 and gaseous pollutants. We used K-means clustering to identify groups of individuals with similar levels of PM2.5 components, selecting groups via cluster stability analysis. Relative rates (RRs) and 95% confidence intervals (95% CIs) for the association between air pollutants and TDLU counts were estimated from a zero-inflated negative binomial regression model adjusted for potential confounders.ResultsPM2.5 total mass was associated with higher TDLU counts among all women (interquartile range (IQR) increase, RR = 1.06; 95% CI: 1.01-1.11). This association was evident among both premenopausal and postmenopausal women (premenopausal RR = 1.05, 95% CI: 1.00-1.11; postmenopausal RR = 1.11, 95% CI: 1.00-1.23). We identified 3 groups corresponding to clusters that varied geographically and roughly represented high, medium, and low levels of PM2.5 components relative to population mean levels. Compared to the cluster with low levels, the clusters with both high (RR = 1.74; 95% CI: 1.08-2.80) and medium (RR = 1.82; 95% CI: 1.13-2.93) levels were associated with higher TDLU counts; although not significantly different, the magnitude of the associations was stronger among postmenopausal women.ConclusionsHigher PM2.5 levels were associated with reduced TDLU involution as measured by TDLU counts. Air pollution exposure may influence the histologic characteristics of normal tissue which could in turn affect breast cancer risk.

Dataset Information

Postlactational involution biomarkers plasminogen and phospho-STAT3 are linked with active age-related lobular involution.

Purpose

Methods

Results

Conclusions

Publications

Postlactational involution biomarkers plasminogen and phospho-STAT3 are linked with active age-related lobular involution.

Similar Datasets

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