Complementary role of Ki67 index and 70-gene signature (MammaPrint) high-risk patients in the St Gallen risk group with uncertain chemotherapy suggestion.

Abstract

579 Background: St Gallen (SG) Consensus Panel on adjuvant treatment recommends the use of proliferation markers and multigene assays when choosing the appropriate treatment in addition to traditional parameters. Ki67 predictive/prognostic value is widely accepted; we tested its role in increasing the accuracy of risk prediction among Mammaprint (MP) /High(HR) or /Low Risk (LR) breast cancer patients with a SG risk uncertain for chemotherapy selection. Methods: MP was determined (courtesy of Agendia, Amsterdam) in 3 Italian Hospitals on 305 consecutive samples of breast cancer patients. We focused on SG “Intermediate Risk” Group (HER2 neg, no VI and: ER>10<50%, or G2 or Ki67 >15<30% or N1a or T>2<5cm), where the indication for adjuvant CHT still remains uncertain. In MP/HR cases, a “low” Ki67 value (<15%) was used to eliminate CHT suggestion and viceversa an “intermediate” Ki67 value (>15<30%) in MP/LR cases. Results: Overall, 72/305 pts (26.6%) were in SG intermediate risk group with a median age of 64 years (26-98). Ki67 was non available in 4.1% of cases, MP rejected in 16.6%, HR was detected in 39 (54.2%), whereas LR in 21 (29.2%). Ki67 resulted low in 23 MP/HR cases (59%), intermediate in 6 MP/LR cases (28.5%) and in 3 out 12 MP/Rejected cases (25%). The overall concordance between MP and Ki67 was 28/57 (49.1%), MP rejected excluded. Overall MP suggested 39/60 CHT (65%), Ki67 29/69 (42%). Conclusions: The risk of relapse is a continous variable and MP evaluates it in a dichotomy (low vs high) wich could decrease the accuracy of the test. In the selected SG Group, the average risk of 5 yr relapse is around 20% (EBCTCG, Lancet 2011) and MP HR cases in our experience account for 55%. A low Ki67 value could help avoid more than 20% of cytotoxic treatments suggested by MP. In the same way, according to an ER value <50% (2 cases), an intermediate Ki67 value could suggest a more aggressive treatment in a further 13% of cases MP LR (6/21) or Rejected (3/12). MP probably overestimates the risk in 20% of cases and underestimates it in further 20%. Ki67 could be usefull for a more personalized treatment in patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain.