Pathologic complete response of ductal carcinoma in situ to neoadjuvant systemic therapy in HER2-positive invasive breast cancer patients: a nationwide analysis

Abstract Purpose Ductal carcinoma in situ (DCIS) is present in more than half of HER2-positive invasive breast cancer (IBC). Recent studies show that DCIS accompanying HER2-positive IBC can be completely eradicated by neoadjuvant systemic therapy (NST). Our aim was to determine the percentage of pathologic complete response of the DCIS component in a nationwide cohort and to assess associated clinicopathologic variables. Furthermore, the impact on surgical treatment after NST was investigated. Methods Women diagnosed with HER2-positive IBC, treated with NST and surgery, between 2010-2020, were selected from the Netherlands Cancer Registry. Pre-NST biopsy and postoperative specimen pathology reports were obtained from the Dutch Nationwide Pathology Databank, and assessed for presence of DCIS. Clinicopathologic factors associated with DCIS response were assessed using logistic regression analyses. Results A DCIS component was present in the pre-NST biopsy in 1443 of the 5834 included patients (24.7%). Pathologic complete response of the DCIS component was achieved in 743 (51.5%) of these patients. Complete response of DCIS occurred more frequently in case of complete response of IBC (63.4% versus 33.8%, p<0.001). ER-negative IBC (OR 1.79; 95%CI 1.33-2.42) and treatment with HER2-targeted therapy (OR 5.97; 95%CI 1.82-19.55) were associated with complete response of DCIS. Mastectomy rates were higher in IBC+DCIS compared to IBC (53.6% versus 41.0%, p<0.001). Conclusion Pathologic complete response of DCIS occurred in 51.5% of HER2-positive IBC patients and was associated with ER-negative IBC and complete response of IBC. Future studies should investigate imaging evaluation of DCIS response to improve surgical decision making.