Her2 and Ki67 Biomarkers Predict Recurrence of Ductal Carcinoma in Situ

A subset of patients with ductal carcinoma in situ (DCIS) experience recurrence or progression to invasive cancer. Current clinical practice is not reliably guided by DCIS recurrence prediction, although recurrence risk for invasive breast cancer can now be assessed. We analyzed a panel of biomarkers (estrogen receptor, Her2, Ki67, p53, cyclin D1, COX-2, caveolin-1, survivin, and PPAR-γ) and DCIS histologic and clinical features to determine associations with DCIS recurrence.

Seventy DCIS cases diagnosed between 1995 and 2010 were divided into 2 groups: 52 had DCIS without known recurrence after excision and 18 had DCIS with subsequent recurrence after excision as DCIS or invasive carcinoma in the ipsilateral or contralateral breast. Tissue microarrays were prepared, immunohistochemistry performed, and expression of the biomarkers scored semiquantitatively. Variables analyzed included age, tumor size, margin status, DCIS grade, necrosis, histologic type, and immunohistochemistry scores. Differences between groups were evaluated using t tests for continuous variables and Fisher exact tests for categorical variables.

Intraductal necrosis was associated with increased recurrence risk: 46% of nonrecurrent cases showed necrosis compared with 83% of those who recurred (P=0.007). Her2 (human epidermal growth factor receptor 2) and Ki67 expression distributions were significantly different between nonrecurrent and recurrent cases. Her2 was overexpressed in 14% of nonrecurrent cases compared with 50% in the recurrent cases (P=0.03). A total of 87% of nonrecurrent cases had low Ki67 staining (0% to 10%) compared with 50% among the recurrent cases (P=0.002).

Our results suggest that Her2 and Ki67 immunohistochemistry and the presence of intraductal necrosis aid in DCIS risk stratification.