Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer

Abstract

BackgroundPatients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy. However, the significance of chemotherapy for those with luminal tumours has decreased due to recent changes in treatment strategies. Thus, it is often difficult to determine whether we should recommend chemotherapy to such patients in clinical practice. We investigated Ki67 expression, as a means of predicting the responses of luminal HER2-negative breast cancer patients to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that would benefit from these treatments.MethodsWe enrolled 114 luminal HER2-negative breast cancer patients undergoing surgery after NAC. Biomarkers were examined using biopsy specimens obtained prior to treatment, to avoid any chemotherapy-related effects. Chemotherapy effects were determined employing operative specimens and we defined pathological complete response (pCR) as invasive nest disappearance, based only on the primary breast tumour. We applied receiver operating characteristic curve analysis to data from our 114 patients, to investigate Ki67 expression as a predictor of pCR.ResultsThe pCR rate was significantly higher for tumours with high Ki67 expression (p < 0.01) and all patients who obtained pCR remained recurrence-free during the median 58-month observation period. We identified 35% as the Ki67 cut-off value which distinguishes those with a pCR from other cases. Another dataset, comprised of 196 patients with a median 29-month observation period, was recruited for validation. Disease-free survival was found to be significantly (p < 0.01) lower in the patients with tumours in which Ki67 expression was higher than 35%.ConclusionOur results raise the possibility of the luminal HER2-negative subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy, as evidenced by improved survival.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-550) contains supplementary material, which is available to authorized users.

Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

“…High Ki67 expression at baseline is significantly associated with improved pCR rates , primarily in the triple‐negative and HER2‐positive BC subtypes . The potential prognostic value of Ki67 after NAC is less well known .…”

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

“…Ki67 expression has not been used so far to predict therapeutic response in HCC. However, numerous studies have shown that high expression of Ki67 was a good predictor of sensitivity to neoadjuvant chemotherapy in breast cancer, suggesting that Ki67 could also be a reliable biomarker to predict tivantinib response in HCC (31)(32)(33).…”

Concurrent neoadjuvant chemotherapy and estrogen deprivation in patients with estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (CBCSG‐036): A randomized, controlled, multicenter trial

“…Specifically, patients with a higher baseline Ki‐67 level (>20%) responded better to concurrent treatment and patients with a lower Ki‐67 level did not, and the interaction was found to be significant . We speculated that tumors with low Ki‐67 tended to be of the “luminal A‐like” subtype, indicating less sensitivity to chemotherapy . Furthermore, Skriver et al demonstrated that a tumor size <2 cm and lymph node‐negative status were significantly associated with a better response to NET, whereas the majority of patients enrolled in the current study presented with either a large tumor size or lymph node metastasis, which also might limit the efficacy of NET among such a subgroup of patients with an indolent tumor subtype (Ki‐67 ≤20%).…”

“…28 We speculated that tumors with low Ki-67 tended to be of the "luminal A-like" subtype, indicating less sensitivity to chemotherapy. 29 Furthermore, Skriver et al 30 demonstrated that a tumor size <2 cm and lymph node-negative status were significantly associated with a better response to NET, whereas the majority of patients enrolled in the current study presented with either a large tumor size or lymph node metastasis, which also might limit the efficacy of NET among such a subgroup of patients with an indolent tumor subtype (Ki-67 ≤20%). In addition, some previous studies have reported that large tumors with a low Ki-67 level were more likely to present with autophagy activation after NCT to escape from chemotherapy cytotoxicity, which could, to some extent, impair endocrine treatment.…”