Temporal Dynamics and Black-White Patient Differences in Contralateral Invasive Breast Cancer Risk Following DCIS and IDC: A Time-Varying Competing-Risks Analysis

Background/Aim: The time-varying effects of risk factors on contralateral invasive breast cancer (CIBC) after primary ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) have not been fully explored. Patients and Methods: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying effects were assessed using a time-varying-coefficient Fine-Gray competing risks model, depicted by cumulative regression coefficient and subdistribution hazard ratio [sHR(t)] curves. Cause-specific hazard ratio [HR(t)] curves served as sensitivity analyses. Mortality HR(t) curves and landmark competing-risk analyses were used to aid result interpretation. Results: A total of 596,103 women with a first primary DCIS or IDC (2000-2020) were included. For DCIS, age 51-60 years and tumor with size >5 cm posed persistent risks; age 61-70, ≥71 years, and micropapillary histology showed an early high risk that attenuated. Endocrine therapy’s protective effect waned. For IDC, age 51-60 years was a persistent risk factor; hormone receptor positivity, N1 lymph node metastasis, and chemotherapy showed persistent inverse associations with CIBC risk. Age 61-70, ≥71 years, lymph nodal metastasis stages 2-3 (N2/N3), and tumor with size >5 cm exhibited early high risk with later attenuation. Notably, as observed in the curves, Black patients appeared to show higher peak risks for a subset of risk factors but shorter high-risk periods versus White patients. Conclusion: Under the competing risk of death, some risk factors for CIBC after DCIS and IDC exhibit significant time-varying effects, with potential differences between Black and White patients. These findings may help develop individualized screening strategies and reduce the use of contralateral prophylactic mastectomy (CPM).