Ductal carcinoma in situ is regarded as a non-obligate pre-invasive precursor of invasive ductal carcinoma. Up to one in four patients will recur locally after breast-conserving surgery alone, and approximately half of these recurrences will be invasive. Recurrence prediction is still not satisfactorily accurate and could be improved by identifying additional prognostic markers.
As the role of the tumour microenvironment in cancer progression is increasingly acknowledged, this PhD research project aimed to explore the prognostic potential of stromal features in ductal carcinoma in situ. The presence of periductal myxoid stroma was identified as an adverse prognostic factor for both overall and invasive recurrence risk. This myxoid stromal architecture correlated with reduced stromal decorin expression and increased periductal versican expression. The cytokines bFGF and TGF-β1 were identified as potent modulators of stromal protein expression. We hypothesise that certain preinvasive ductal carcinoma in situ lesions modulate the composition of their surrounding stroma through cytokine release. This invasion-permissive and tumour-promoting microenvironment is mirrored in the presence of a myxoid stromal architecture. Further studies are required to validate the value of stromal changes as prognostic markers for recurrence in ductal carcinoma in situ.