HER2 overexpression in ductal carcinoma in situ is associated with ipsilateral breast cancer recurrence after conservative surgery

BACKGROUND: A few patients with ductal carcinoma in situ (DCIS) after breast conservative surgery would develop ipsilateral breast cancer recurrence (IBTR), either invasive or non-invasive. Study of accurate predictive biomarkers for IBTR risk are warranted. We analyzed the association of human epidermal growth factor receptor 2 (HER2) status with IBTR after conservative surgery. METHODS: We chose 213 cases of DCIS diagnosed between 2005 and 2010. Immunohistochemistry was performed for ER, PR, and HER2. The primary endpoint was IBTR. Kaplan-Meier plot was used for univariate survival analysis with log-rank test. Cox proportional hazards model was used for multivariate analysis. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: With a median follow-up 80 months, there were 29 IBTR events. In univariate analysis, patients with high grade, ER-negative, and HER2-positive breast cancers tended to have an increased risk of IBTR. In multivariate analysis, grade III and HER2-positivity were independent predictive factors for IBTR. HER2-positive DCIS had a 2.6-time risk of recurrence compared with those with HER2-negative tumors (HR=2.60; 95% CI, 1.02–6.98; P=0.044). For HER2-equivocal cases, the HR was 1.59 (95% CI, 0.40–6.34; P=0.50) compared with HER2-negative cases. Moreover, annual recurrence pattern according to HER2 status showed that HER2-positive DCIS had a recurrence peak at 3–5 years (0.3% per annum) while the annual recurrence rate of HER2-negative DCIS was very low (less than 0.1% per annum). CONCLUSIONS: This study suggests that of HER2-overexpression might contribute to IBTR in DCIS after breast conservation.