p53 accumulation is a strong predictor of recurrence in estrogen receptor‐positive breast cancer patients treated with aromatase inhibitors

Abstract

Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)-positive breast cancer in postmenopausal women. However, factors predictive of the efficacy of aromatase inhibitors, and prognostic factors, both for early and late recurrence in women treated with adjuvant aromatase inhibitors have not been identified. Whole genome analysis identified that a TP53 gene mutation exists in ER-positive breast cancers, although the frequency of TP53 gene mutation in luminal tumors is lower compared with basal-like or human epidermal growth factor receptor type 2 (HER2)-positive breast cancers. We examined expression of p53, as well as ER, progesterone receptor, HER2 and Ki-67 using immunohistochemistry in postmenopausal ER-positive breast cancer patients who were treated with aromatase inhibitors as adjuvant endocrine therapy. There were 53 (21%) tumors that contained 10% or more p53-positive cells. High p53 expression was positively correlated with tumor grade, HER2 score and Ki-67 expression. Significant association was observed between disease-free survival and high p53 expression in multivariate analysis (P < 0.0001). Compared with women without recurrence, women with early recurrence had significantly higher p53 expression (P < 0.0001), as did women with late recurrence (P = 0.037). The present study demonstrates that p53 accumulation is a strong predictor of both early and late recurrence in ER-positive breast cancer patients treated with aromatase inhibitors as adjuvant endocrine therapy. TP53 gene alteration might be a key biological characteristic of ER-positive breast cancer.

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

“…12 In agreement with the observation by Kobayashi et al, 61 our finding that p53 positive is connected with the progression of carcinoma to a higher histological grade and Her-2 overexpression in breast cancer patients suggests that p53 positive could be used as a prognostic biomarker for breast cancer 56,[62][63][64] in addition to being used as a diagnostic biomarker. 38 Our findings that Ki-67 positive is connected with the progression of carcinoma to a higher histological grade as well as Her-2 overexpression in breast cancer patients are consistent with the previous observations 5,35,50,61 and increase the reliability of this emerging biomarker 38 as a predictor of breast cancer prognosis outcomes.…”

p53: Protection against Tumor Growth beyond Effects on Cell Cycle and Apoptosis

“…p53 protein accumulation is found to be associated with aromatase inhibitors resistance, and nuclear accumulation is suggestive of mutations in the TP53 gene. p53 has been considered as a prognostic biomarker in oncology, with p53 overexpression being associated with a shorter disease-free interval, and both early and late recurrence in ER-positive postmenopausal breast cancer patients treated with aromatase inhibitors (66,67). Taken together, p53 status has potential prognostic value for estrogen-dependent postmenopausal breast cancer.…”

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

“…It is necessary to collect evidence regarding p53 accumulation and establish the methodology for clinical practice. Further studies on p53 as a predictive factor for late recurrence and adjuvant chemotherapy are required, along with the findings of previous reports (15,17). This study's limitations include its retrospective design at a single institution, the heterogeneity of the administered treatments, and the short follow-up period.…”

“…The prognostic significance of p53 protein expression in ER-positive and HER2-negative breast cancer has been reported in a limited number of studies (14)(15)(16)(17). However, several items of information are required for the interpretation of p53 protein expression.…”

“…Recent studies have demonstrated that abnormalities of the p53 gene and accumulation of the p53 protein in the nuclei are prognostic indicators in ER-positive and HER2-negative breast cancer patients (14)(15)(16)(17). Whole-genome analysis identified the presence of a p53 gene mutation in 12% of luminal A and 32% of luminal B breast cancers (18).…”