Prognostic significance of Ki-67 in node-negative (pN0), triple-negative (TN) breast cancer (BC).

Abstract

1056 Background: TNBCs occur more frequently in younger women, tend to relapse and metastasize early and have a poor prognosis. They are associated with a range of adverse features including high Ki-67 values. The aim of this analysis was to investigate if Ki-67 could help to identify different prognostic subgroups within the primary pN0 TNBCs. Methods: Patients (pts) with pN0 BC and with ER negative (0%), PgR negative (0%), HER2 scores of 0 and/or FISH not amplified were identified through the institutional clinical database. All pts underwent surgery at the European Institute of Oncology, Milan, Italy, between January 1997 and December 2005 and did not receive neoadjuvant treatment. The association between Ki-67 and other tumour characteristics was evaluated with the Kruskal-Wallis test. The relationship between Ki-67 and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were applied to the Cox model to analyze Ki-67 as a continuous variable. Results: We identified 496 consecutive pN0 M0 TNBC pts with a median age of 52 years; 443 pts underwent quadrantectomy (89%), and 425 pts (86%) received adjuvant chemotherapy, mainly classical CMF (n=315/425 pts, 74%). The median Ki-67 was 48% (range 4-95). The median follow up was 6 years (range 0.5 −13). Total deaths and deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67 was significantly higher in ductal TNBC when compared to other histological types (p<0.01). Moreover, Ki-67 increased with decreasing age (p<0.01), increasing tumour size (p<0.01) and grade (p<0.01). When analyzing Ki-67 as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67 up to about 35% and remained flat thereafter (adjusted effect of Ki-67 P=0.049; adjusted non-linear effect P=0.021). Accordingly, when dividing pts into lower (≤35%)and higher (>35%) Ki-67 subgroups, the 5−year cumulative incidence of breast related deaths were 2.3% and 9.0%, respectively, with an adjusted HR>35 vs ≤35of 2.5 (95% CI 1.0 – 6.0, p=0.046). Conclusions: Within the group of pts with pN0 TNBC, Ki-67 value was associated with different prognoses. Ki-67 value might be useful in the design of trials of risk-adapted adjuvant therapies.