Time-varying effect and long-term survival analysis in XXXX @entity1 treated with neoadjuvant chemotherapy.

@entity5 @entity1 @entity0
BACKGROUND: Recent studies have indicated the prognostic value of @entity5 subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. METHODS: Prognostic factors from 956 consecutive @entity0 @entity1 treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. RESULTS: The prognostic value of @entity5 histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: @entity5 size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological @entity5 grade. The 'prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after @entity5 diagnosis, the hazard ratio of distant recurrences in @entity1 with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological @entity5 grade followed a similar trend. The hazard ratio of grade III @entity1 compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR @entity1 was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade @entity5 presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. CONCLUSION: From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within @entity1 who receive NAC are influenced by achieving pCR and @entity0 subtype. @entity5 with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR @entity1 remain at risk for distant recurrence for many years.
