Prognostic estimates of Ki-67 percentage drop after neoadjuvant chemotherapy (NAC) in luminal B (lumB) and triple negative breast cancer (TNBC)

Abstract

Background: Pathologic complete response (pCR) and residual cancer burden (RCB) after NAC are validated prognostic markers in BC. We assessed the impact of adding Ki-67% drop (baseline biopsy - surgery) to distant metastasis relapse-free survival (dRFS) models containing CP factors plus post-treatment stage (MDACC CPS score), estrogen receptor status and tumor grade (MDACC CPS+EG score). Method(s): Records from 341 patients (pts) with lumB/HER2 neg (baseline Ki67 >20%) or TNBC who received NAC from 2008 to 2015 at our hospital were reviewed. Uni- and multivariate Cox models were constructed and concordance-index (c-index) calculated. Result(s): Pts: median age 47 years (24-83), 60% lumB and 40% TNBC, 62% stage 2, 38% stage 3. pCR: 12% lumB, 32% TNBC (p<0.01). Median Ki-67% drop: 24% lumB, 5% TNBC (p<0.01), without differences by NAC regimen. dRFS at 5 yearmedian follow-up was 75% in lumB (CI95%67-83) vs 62% in TNBC (CI95% 53-74, p<0.01); 90% in RCB 0/1 (CI95% 81-97) vs 74% in RCB 2/3 (CI95% 65-83, p<0.01). As compared to pts with RCB 0/1, those with RCB 2/3 plus Ki-67% drop>= 20% (best cut-off in univariate model) had similar dRFS at 5 years (90%, CI95% 81-100, p=0.48), irrespective of molecular group. Enrichment for Ki-67>=20% drop in lumB (60%) vs TNBC (30%, p<0.01) was observed. Both CPS and CPS+EG scores were validated as independent prognostic factors in univariate dRFS models (c-index of 0.70 and 0.78, respectively). The addition of Ki-67% drop (< 20% vs>= 20%) to CPS and CPS+EG scores in multivariable models significantly improved their performance (c-index of 0.74 and 0.81, respectively). Ki-67>=20% drop associates with 70-80% reduction in distant relapse risk (HR 0.27 and 0.16 in CPS and CPS+EG models, respectively, p<0.05). Conclusion(s): Our data support the addition of Ki-67% drop after NAC in lumB and TNBC to existing dRFS online outcome calculators. In the context of RCB 2/3, Ki- 67>= 20% drop is mainly seen in lumB/HER neg tumors. Importantly, Ki-67 < 20% drop identifies a high-risk population that may be eligible to clinical trials with novel therapeutic interventions in the adjuvant setting.