A prognostic model for distant recurrence-free survival in triple-negative breast cancer (TNBC) and the outcomes of initiation of adjuvant chemotherapy in the risk of relapse.

Abstract

530 Background: TNBC is a highly complex, heterogenous disease associated with poor outcomes, high incidence of distant metastases, and limited treatment options. With the purpose of identify patients at different risk of distant recurrence, we developed a prognostic model using clinicopathological characteristics that contribute to the risk of recurrence in TNBC patients and also evaluate its influence in the time of beginning of adjuvant therapy. Methods: We retrospectively analyzed 687 TNBC patients who received adjuvant chemotherapy between January 2000 to December 2014 at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). The database was randomly divided into two groups to create a discovery set (n = 344) and a validation set (n = 343). Univariate and multivariate Cox regression analysis was conducted to identify prognostic factors for distant recurrence-free survival (DRFS). We developed a linear risk score based on clinicopathologic characteristics. Under STEPP methodology we classified patients at high, intermediate or low-risk of distant recurrence and the absolute treatment effects of time to initiation of chemotherapy (TTC, ≤ 30 vs > 30 days) through risk subgroups was estimated. Results: The median of follow-up was 9.90 years. In total, 31.0% (n = 213/687) relapses were registered. Variables associated with DRFS in the multivariate analysis were: age, T-staging, and N-staging. A tumor staging of T3-T4 vs. T1/T2 (HR = 2.92, 95%CI: 1.39 - 6.17), followed by the number of positive lymph nodes (N2-N3 vs N0/N1; HR = 2.78, 95%CI: 1.74 - 4.45) and an older age (≥ 60 years vs. ≤ 40/41-59, HR = 2.66, 95%CI: 1.46 - 4.88) were the clinicopathologic characteristics contributing to a higher risk score according to the 3-variable model. Also, 3 risk groups were identified and corroborated in the validation group. In the discovery set, patients with a TTC > 30 days experienced an overall decreased of 17.5% (95%CI: 6.7 - 28.3) in 10-year DFRS vs. those who initiated adjuvant therapy before 30 days. The impact of TTC > 30 days was higher in patients classified as high-risk (Decreased 10-year DFRS: 53.3 ± 28.8 %), similar findings were found in the validation set. Conclusions: A prognostic model based in clinicopathological characteristics (age, pT and pN), was able to classify TNBC patients’ candidates to adjuvant chemotherapy in 3 prognostics groups. We identified a subgroup of patients in which delaying of adjuvant chemotherapy (> 30 days) confers very high-risk of relapse.