Biological behavior of DCIS with or without microinvasion. Same and different.

Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer, detected mostly due to associated calcifications. Although non-invasive and primarily treated with surgical excision, recurrence as in situ or invasive form occurs in a substantial subset of DCIS patients. Microinvasion, defined as less than or equal to 1mm invasive focus poses a diagnostic, biological and therapeutic dilemma, as the exact biological behavior of DCIS with or without microinvasion is controversially understood. In this retrospective study based on standardized pathology reports from a single center, we addressed the question if DCIS with or without microinvasive foci represents biologically one disease or two distinct entities. We identified 148 patients with surgically treated DCIS and complete clinico-pathological data and follow-up information, 126 of 148 (85.1%) pure form, 22 of 148 (14.9%) with microinvasive foci. Events in follow-up (in-situ, invasive recurrent disease, breast cancer related death) were correlated with the presence of microinvasive foci and with pathological parameters (DCIS size, nuclear grade, the presence of necrosis, margin status, biomarkers, hormone receptors and Ki67 index) and clinical information (therapy modalities). Overall time-to-event-probability (TTE) was assessed with Kaplan Meier curves. There was a total of 28 events (18.9% of cohort). 12 of 148 (8.1%) patients had recurrent DCIS, 16 of 148 (10.8%) developed invasive breast cancer, 5 of 148 (3.4%) patients died related to breast cancer in follow-up. DCIS with/without microinvasion did not differ significantly in TTE. There was a non-significant trend for worse 5-year breast cancer related death in DCIS with microinvasion. DCIS with microinvasion developed significantly more often in-situ or invasive recurrences in extensive disease (≥5cm) (p=0.040), with nuclear high grade (p=0.045), with necrosis present (p=0.045), with narrow resection margins (>1mm) (p =0.006), with younger age (≤50 years) in follow-up (p= 0.025) and in the absence of adjuvant radio- and / or endocrine therapy (p=0.009, p= 0.034). No further factors such as calcification, positive margins, hormone receptor status had an impact on TTE on DCIS with or without microinvasive foci. Our data shows that biological behavior of DCIS with microinvasive foci per se does not differ from pure DCIS in TTE. However, in-situ or invasive recurrences (total or ipsilateral) occur more often in microinvasive DCIS with extensive disease, with nuclear high grade, present necrosis, with narrow resection margins and in younger age in follow-up. These data warrant for further studies to understand the biology of DCIS with microinvasion and to evaluate specific therapy options different from pure DCIS potentially involving adjuvant modalities.