Accumulation of p53 is prognostic for aromatase inhibitor resistance in early-stage postmenopausal patients with ER-positive breast cancer

Abstract

Xiao-qing Jia,1 Qi Hong,1 Jing-yi Cheng,2 Jian-wei Li,1 Yu-jie Wang,1 Miao Mo,3 Zhi-min Shao,1 Zhen-zhou Shen,1 Guang-yu Liu1 1Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Objective: Studies have indicated that p53 protein accumulation exerts an adverse effect on the survival of breast cancer patients; however, the prognostic value of p53 protein accumulation for aromatase inhibitor (AI) resistance in ER-positive breast cancer is uncertain.Methods: The expression level of p53 protein was detected by immunohistochemistry in primary early-stage ER-positive breast tumor specimens from 293 postmenopausal breast cancer patients who received first-line AI treatment (letrozole, anastrozole, or exemestane) until relapse, and analysis was performed to determine whether expression of p53 protein affected the response to endocrine therapy.Results: Of the 293 invasive ductal carcinomas, 65.4% were positive for p53 protein expression. All patients received AI therapy as first-line treatment until relapse. The 5-year disease-free survival rates in p53-positive and p53-negative patients were 78% and 89%, respectively. Patients with primary breast tumors that had p53 protein accumulation showed significantly more resistance to AI treatment (hazard ratio=1.729, 95% confidence interval=1.038–2.880, P=0.035).Conclusion: This study demonstrated that p53 protein accumulation was helpful in choosing patients who may benefit from AI treatment and is a prognostic marker in ER-positive early-stage breast cancer. Keywords: p53, breast cancer, prognosis, endocrine resistance