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

• Published in: Cancer science Vol. 105; no. 1; pp. 81 - 88
• Main Authors: Yamamoto, Mitsugu, Hosoda, Mitsuchika, Nakano, Kiichiroh, Jia, Shusheng, Hatanaka, Kanako C., Takakuwa, Emi, Hatanaka, Yutaka, Matsuno, Yoshihiro, Yamashita, Hiroko
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2014; BlackWell Publishing Ltd
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal - therapeutic use; Aromatase; Aromatase inhibitor; Aromatase Inhibitors - therapeutic use; Biomarkers; Biopsy; Body mass index; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer therapies; Cell cycle; Cell Line, Tumor; Chemotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Endocrine therapy; Epidermal growth factor; ErbB-2 protein; Estrogen receptors; Estrogens; Female; Genomes; HeLa Cells; Humans; Immunohistochemistry; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Lymphatic system; MCF-7 Cells; Medical prognosis; Menopause; Metastasis; Middle Aged; Multivariate analysis; Mutation; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Original; p53; p53 Protein; Point mutation; Post-menopause; Postmenopause; Progesterone; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - biosynthesis; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Receptors, Progesterone - genetics; Receptors, Progesterone - metabolism; Studies; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Womens health; breast cancer; Aromatase inhibitor; prognosis; endocrine therapy; p53
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12302

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. Expression of p53, as well as expression of ER, PgR, HER2 and Ki67 by immunohistochemistry were investigated in postmenopausal ER‐positive breast cancer patients who were treated with aromatase inhibitors as adjuvant endocrine therapy. Our study demonstrates that p53 accumulation is a strong predictor of both early and late recurrence.