Evaluating the Risk of Upstaging HER2-Positive DCIS to Invasive Breast Cancer

Background: Overexpression of human epidermal growth factor 2 (HER2) in invasive breast cancer (IBC) is an independent poor prognostic factor. However, the significance of HER2 overexpression in ductal carcinoma in situ (DCIS) is not well defined. The current study assessed the correlation of HER2⁺ DCIS with the rate of upstaging to IBC on the final pathology. Methods: The study retrospectively analyzed patients with the diagnosis of DCIS on core needle biopsy (CNB) at the authors’ institution from 2009 to 2016. Data were analyzed using two-sample t tests. Multivariate analysis was performed using logistic regression. Results: The study found that HER2⁺ DCIS had significantly higher rates of upstaging to IBC than HER2⁻ DCIS (odds ratio [OR] 1.89; p = 0.012). In addition, triple-positive disease was more than two times more likely to be upstaged (OR 2.5; p = 0.01), whereas patients with estrogen (ER)-positive, progesterone (PR)-positive, and HER2⁻ diseases were half as likely to be upstaged (OR 0.5; p = 0.04). Upstaging did not differ for patients with triple-negative disease (OR 0.89; p = 0.8). Additionally, patients with HER2⁺ DCIS were significantly younger regardless of ER/PR status (p = 0.03). The overexpression of HER2 in patients with an initial diagnosis of DCIS on CNB were twice as likely to have IBC on the final pathology as those who did not. Conclusion: The results suggest that overexpression of HER2 may serve as a biomarker for risk stratification of patients with DCIS and may help to guide treatment strategies in the future. For institutions in which HER2 testing may be performed on DCIS, patients should be counseled appropriately about the risk of upgrade to IBC.