Prognostic value of Ki67 and p53 in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer: Validation of the cut-off value of the Ki67 labeling index as a predictive factor

Abstract

Abstract. The aim of this study was to evaluate the significance of the Ki67 labeling index and p53 status as prognostic and predictive indicators of operable estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Among 697 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2013, 308 patients with ER-positive and HER2-negative breast cancer were assessed. The results of the multivariate Cox analysis demonstrated that a high Ki67 labeling index was significantly associated with a short recurrence-free interval (RFI) (P=0.004) and was marginally associated with a worse overall survival (P= 0.074). A positive p53 status was not associated with worse outcomes. To validate the cut-off values of the Ki67 labeling index for identifying patients who may benefit from additional chemotherapy, prognostic factors were investigated in breast cancer patients treated postoperatively with endocrine therapy alone. Analysis of receiver operating characteristic curves demonstrated that a Ki67 labeling index cut-off of 20.0% was optimal for predicting recurrence among patients who did not receive adjuvant chemotherapy. The 5-year RFIs for patients with Ki67 <20 and ≥20% were 97.2 and 86.6%, respectively (P= 0.0244). A high Ki67 labeling index (≥20%) was significantly associated with large tumors (P<0.01), lymph node metastasis (P=0.0236) and positive p53 status (P<0.001). The univariate analysis demonstrated that Ki67 labeling index ≥20%, lymph node metastasis and progesterone receptor negativity were significant worse prognostic factors for RFI (P=0.0333, 0.0116 and 0.0573, respectively). The Ki67 labeling index was found to be a useful prognostic factor in patients with ER-positive and HER2-negative breast cancer and the cut-off values of the Ki67 labeling index for making a decision regarding adjuvant treatment were validated. IntroductionFor the majority of patients with early breast cancer, adjuvant systemic therapy is recommended following primary surgery to reduce the risk of breast cancer recurrence and to increase the likelihood of a cure. Approximately 70% of breast cancers express estrogen receptor (ER), and ER status is a powerful predictor of response to therapies that inhibit estrogen synthesis or block the action of its receptor (1). Endocrine therapies are established in the adjuvant setting (2-4). It is important to distinguish patients with ER-positive tumors at high risk for recurrence who require additional chemotherapy, from those for whom adjuvant endocrine therapy alone may suffice, as the economic burden and toxicities of chemotherapy must be minimized (5). Multi-gene assays are strong candidate tools for predicting the risk of recurrence in ER-positive patients (6). However, classification using multi-gene expression analyses is not appropriate for everyday practice. According to the St. Gallen Consensus Conference held in 2013, the intrinsic subtype affects the indication for adjuvant chemotherapy and surrogat...

<p>Prognostic Value of Ki67 in Patients with Stage 1–2 Endometrial Cancer: Validation of the Cut-off Value of Ki67 as a Predictive Factor</p>

“…24–26 In female malignant tumors, the cut-off value of Ki67 has been used as an important prognostic indicator of breast cancer. 4 While in endometrial cancer, Ki67 has also shown its potential value, but there is no acceptable cut-off value currently. In this study, we found an optimal cut-off value (38%) of Ki67 for predicting the recurrence of endometrial cancer and multivariate Cox regression analysis suggested that high Ki67 labeling index (≥38%) was an independent risk factor for stages I–II endometrial cancer recurrence.…”

“… 3 In many other related studies, various cut-off values of Ki67 labeling index have also been determined for postoperative management of breast cancer. 2 , 4 In endometrial cancer, the risk of recurrence is usually determined by the patient’s pathological diagnosis, including staging, histological subtype, tumor grade, lymph node status, and depth of muscular invasion. 5–7 However, more and more studies show that Ki67 can be used as an important prognostic predictor of endometrial cancer, 1 , 8 , 9 but currently there is still no recognized acceptable cut-off value of Ki67 in endometrial cancer.…”

Nonviral Gene Therapy for Cancer: A Review

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