A Prognostic Model for Triple-Negative Breast Cancer Patients Based on Node Status, Cathepsin-D and Ki-67 Index

Abstract

ObjectiveThe aim of this study was to evaluate clinicopathologic factors that could possibly affect the outcome of patients with triple negative breast cancer and subsequently build a prognostic model to predict patients’ outcome.MethodsWe retrospectively analyzed clinicopathologic characteristics and outcome of 504 patients diagnosed with triple-negative invasive ductal breast cancer. 185 patients enrolled between 2000 and 2002 were designated to the training set. The variables that had statistically significant correlation with prognosis were combined to build a model. The prognostic value of the model was further validated in the separate validation set containing 319 patients enrolled between 2003 and 2006. ResultsThe median follow-up duration was 66 months. 174 patients experienced recurrence, and 111 patients died. Positivity for ≥4 lymph nodes, Cathepsin-D positivity, and Ki-67 index ≥20% were independent factors for DFS, while the lymph nodes status and Ki-67 index were the prognostic factors for OS. The prognostic model was established based on the sum of all three factors, where positivity for ≥4 lymph nodes, Cathepsin-D and Ki-67 index ≥20% would individually contribute 1 point to the risk score. The patients in the validation set were assigned to a low-risk group (0 and 1 point) and a high-risk group (2 and 3 points). The external validation analysis also demonstrated that our prognostic model provided the independent high predictive accuracy of recurrence.ConclusionThis model has a considerable clinical value in predicting recurrence, and will help clinicians to design an appropriate level of adjuvant treatment and schedule adequate appointments of surveillance visits.

A Prognostic Model for Patients with Triple-Negative Breast Cancer: Importance of the Modified Nottingham Prognostic Index and Age

“…Nevertheless, many researchers have observed that tumor size or LN status have a significant association with DFS or OS in TNBC patients [14162021]. Thus, the MNPI, which is calculated with input from tumor size, LN stage, and modified histologic grade, appears to be theoretically appropriate to predict the prognosis of patients with TNBC, and our study revealed that the MNPI is the most significant prognosticator for DFS, DMFS, and OS.…”

“…However, in most studies of TNBC patients, the prognostic significance of nodal status was evaluated by the number of positive LNs, not NR. These studies demonstrated that patients with fewer positive LNs had significantly more favorable DFS and OS [2021]. Recently, Solak et al [22] reported a clearer prognostic separation for TNBC using NR as compared to using pN staging.…”

“…Keam et al [25] reported that TNBCs with high Ki-67 (≥10%) expression were associated with a higher pCR rate than TNBCs with low Ki-67 expression, and high Ki-67 was correlated with poor DFS and OS, paradoxically, in 105 TNBC patients treated with PST. Several recent retrospective studies have consistently suggested that Ki-67 may be a prognosticator in TNBC patients, as well as in patients with luminal type A breast cancer [2026]. However, this needs further study to examine whether the Ki-67 index can be used to subdivide TNBC.…”

Association of ICAM-1, VCAM-1, CYCLIN D1 and Cathepsin D with Clinicopathological Parameters in Breast Carcinoma; an Immunohistochemical Study

“…It was reported that positive cathepsin D results may help to determine the patients with risk and to select more or less aggressive adjuvant therapy for the patients with early stage breast cancer during first 3-year follow-up (18). Huang et al (19) showed triplenegative breast carcinoma were frequently associated with overexpression of cathepsin-D, and with aggressive disease course through lymph node invasion and high cancer cell proliferation/Ki-67 index. Guerra et al (20) reported high level of p53 and cathepsin D, together with down-regulation of Bcl-2 is correlated with aggressiveness in breast carcinoma.…”

The search for optimal cutoff points for apoptosis and proliferation rate in prognostification of early stage breast cancer patients treated with anthracyclines in adjuvant settings

“…In the light of our results, we can speculate that this effect may be more apparent in TNBC. On the other hand, there are some studies presenting contrary results in which lower proliferation rate was associated with better prognosis in patients with TNBC [30,[40][41][42] or in which no relation between Ki-67 LI and survival of women with TNBC was seen [43]. We think that these discrepancies, as suggested by International Ki-67 in Breast Cancer Working Group [26], can be caused by differences between analyzed patient groups according to clinical characteristics and treatment type.…”