Prognostic Impact of Ki-67 Change in Locally Advanced and Early Breast Cancer after Neoadjuvant Chemotherapy: A Single Institution Experience

Abstract

Systemic neoadjuvant chemotherapy (NCT) is a standard treatment for locally advanced breast cancer (LABC) and for selected early breast cancer (EBC). In these settings, the prognostic and predictive role of Ki-67 before and after NCT is unclear. The aim of our study was to investigate the prognostic role of Ki-67 change in patients not achieving pathological complete response (pCR). We retrospectively analyzed data of patients who did not achieve pCR assessing Ki-67 expression pre- and post-NCT. We stratified three groups: high reduction (>20%), low reduction (1–20%), and no reduction in Ki-67. These groups were correlated with clinical and pathological data by χ2 test. We estimated disease-free survival (DFS) and overall survival (OS) using Kaplan–Meier method, and we adopted univariate and multivariate Cox proportional hazard models. We selected 82 patients from a database of 143 patients, excluding those who were metastatic at diagnosis, achieved pCR, or lack data regarding Ki-67. Median age at diagnosis was 54 years (range 30–75); 51 patients were Luminal B, 10 human epidermal growth factor receptor 2 (HER-2) enriched, and 21 triple negative. A significant correlation between high Ki-67 reduction and luminal B HER-2-negative subtype was observed ( p = 0,0035 ). The change in Ki-67 was significantly associated with DFS ( p = 0,0596 ) and OS ( p = 0,0120 ), also at multivariate analysis ( p = 0,0256 for DFS; p = 0,0093 for OS). In particular, as compared to patients with low/no reduction of Ki-67, those with high Ki-67 reduction (>20%) after NCT showed better survival (60% vs. 56% vs. 83% after 5 years from diagnosis, respectively; p = 0.01 ). In conclusion, in our study, Ki-67 change showed a significant prognostic role in breast cancer patients treated with NCT who did not achieve pCR. Crucially, Ki-67 < 20% identifies a high-risk population that may be eligible for clinical trials with novel therapeutic interventions in adjuvant setting.

Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: results from the randomized Phase II NeoMET trial

“…In addition, metformin was administrated with the backbone of chemotherapy in our trial. The absolute decrease of Ki67 after neoadjuvant chemotherapy has been reported to be larger (13.0-14.6%) in previous studies [27,28]. In our study, the Ki67 decrease may be driven by the use of chemotherapy and the effect of metformin may be weakened and no longer signi cant.…”

Biomarker Dynamics and Long-Term Treatment Outcomes in Breast Cancer Patients with Residual Cancer Burden after Neoadjuvant Therapy

“…One of the key observations of our study was the different dynamics of KI-67 expression between the biopsy and surgical specimen among BC subtypes. To the best of our knowledge, the previously published studies evaluated the prognostic role of Ki-67 dynamics in terms of absolute or relative differences [ 45 ] concordance using categorical evaluation [ 46 ] or direction of change [ 47 ]. These approaches do not consider both the baseline levels of Ki-67 and their NAT-induced changes.…”

Neoadjuvant Docetaxel and Capecitabine (TX) versus Docetaxel and Epirubicin (TE) for Locally Advanced or Early HER2-Negative Breast Cancer: An Open-Label, Randomized, Multi-Center, Phase II Trial

“…Studies have shown a high correlation between the Ki-67 index and histological grade [20]. High pretreatment Ki-67 levels are associated with poor prognosis and predictive of better preoperative chemotherapy response [21][22][23][24][25]. There is little data on the predictive value of Ki-67 for chemotherapy agent selection because most previous studies focused on the anthracyclines and taxanes.…”