Unraveling Time-Varying Effects of Risk Factors for Contralateral Invasive Breast Cancer Following Ductal Carcinoma In Situ.

INTRODUCTION: Current studies have not reached a consensus on the factors influencing contralateral invasive breast cancer (CIBC) after ductal carcinoma in situ (DCIS), nor have they examined how these effects vary over time. METHODS: A total of 121,529 women with a first DCIS diagnosis between 2000 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Time-dependent Cox model and landmark analysis with competing risks models assessed factors influencing CIBC and their time-varying effects, illustrated by annual incidence rates. RESULTS: During the 22-year follow-up period, Black patients had a significantly higher risk of developing CIBC than White patients, with this difference predominantly observed during the mid-term follow-up. Compared with younger patients, older patients had a significantly higher early risk of CIBC, but the risk showed a decreasing trend in later years due to competing events such as mortality. Landmark analysis using competing risk models showed that the micropapillary subtype was associated with a higher early-phase risk compared with other nonspecial ductal subtypes. Subgroup analysis of endocrine therapy demonstrated that endocrine therapy significantly reduced the risk of CIBC, but this protective effect diminished over time and disappeared after approximately 10.6 years. CONCLUSIONS: This study is the first to demonstrate that factors such as race, age at diagnosis, and endocrine therapy exert significant and time-varying effects on the development of CIBC following DCIS, which may contribute to reducing overtreatment in DCIS patients.