Background:
Collagen fibers surrounding breast ducts may influence
breast cancer progression.
Syndecan-1 interacts with constituents in the extracellular matrix, including
collagen fibers, and may contribute to
cancer cell migration. Thus, the orientation of
collagen fibers surrounding
ductal carcinoma in situ (
DCIS) lesions and stromal
syndecan-1 expression may predict recurrence.Methods: We evaluated
collagen fiber alignment and
syndecan-1 expression in 227 women diagnosed with
DCIS in 1995 to 2006 followed through 2014 (median, 14.5 years; range, 0.7-17.6). Stromal
collagen alignment was evaluated from diagnostic tissue slides using second harmonic generation microscopy and fiber analysis software. Univariate analysis was conducted using χ2 tests and ANOVA. The association between
collagen alignment z-scores,
syndecan-1 staining intensity, and time to recurrence was evaluated using HRs and 95% confidence intervals (CIs).Results: Greater fiber angles surrounding
DCIS lesions, but not
syndecan-1 staining intensity, were related to positive HER2 (P = 0.002) status, comedo
necrosis (P = 0.03), and negative
estrogen receptor (P = 0.002) and
progesterone receptor (P = 0.02) status. Fiber angle distributions surrounding lesions included more angles closer to 90 degrees than normal ducts (P = 0.06).
Collagen alignment z-scores for
DCIS lesions were positively related to recurrence (HR = 1.25; 95% CI, 0.84-1.87 for an interquartile range increase in average fiber angles).Conclusions: Although
collagen alignment and stromal
syndecan-1 expression did not predict recurrence,
collagen fibers perpendicular to the duct perimeter were more frequent in
DCIS lesions with features typical of poor prognosis.Impact: Follow-up studies are warranted to examine whether additional features of the
collagen matrix may more strongly predict patient outcomes.
Cancer Epidemiol
Biomarkers Prev; 27(2); 138-45. ©2017 AACR.