Application of landmark analysis and piecewise Cox regression to identify features associated with prognosis: A national retrospective cohort study of New Zealand women

Abstract

Background Breast cancer prognosis changes over time in complex ways depending on individual risk factors. This study aimed to analyze how breast cancer outcomes in New Zealand women change over time and identify features associated with breast cancer specific survival and locoregional recurrence across different receptor subtypes.

Methods A retrospective cohort study was conducted using data from Te Rēhita Mate Ūtaetae (Breast Cancer Foundation National Register) on 21,574 women diagnosed with invasive breast cancer between 2000–2019. We applied k-medians survival clustering, landmark analysis, and piecewise Cox regression to identify time-specific risk patterns and prognostic features.

Results Survival improved significantly for women diagnosed more recently. Triple-negative breast cancer had the poorest 5-year breast cancer specific survival but demonstrated better outcomes for women surviving beyond this period. In contrast, ER+/HER2- tumors, associated with favorable short-term outcomes, showed the highest risk of late recurrence and breast cancer mortality beyond 10 years. Younger age at diagnosis (≤44 years) was associated with increased recurrence risks, especially for ER-/HER2+ tumors. Radiation therapy reduced early LRR across subtypes. Tumor grade was inversely associated with late recurrence, while stage 2 disease in ER+ tumors markedly elevated late recurrence odds compared to stage 1.

Conclusions This study demonstrates the dynamic nature of breast cancer prognosis, with key findings emphasizing the time-dependent shifts in risk across receptor subtypes. These findings underscore the importance of personalized, receptor-specific follow-up strategies, including extended monitoring for subgroups at heightened long-term risk.