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.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Stallings-Mann ML,Heinzen EP,Vierkant RA,Winham SJ,Hoskin TL,Denison LA,Nassar A,Hartmann LC,Visscher DW,Frost MH,Sherman ME,Degnim AC,Radisky DCdoi
10.1007/s10549-017-4413-3subject
Has Abstractpub_date
2017-11-01 00:00:00pages
133-143issue
1eissn
0167-6806issn
1573-7217pii
10.1007/s10549-017-4413-3journal_volume
166pub_type
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pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:Breast cancer research and treatment
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pub_type: 临床试验,杂志文章
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