p53 accumulation is a strong predictor of recurrence in estrogen receptor-positive breast cancer patients treated with aromatase inhibitors - PubMed (original) (raw)

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

Mitsugu Yamamoto et al. Cancer Sci. 2014 Jan.

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.

Keywords: Aromatase inhibitor; breast cancer; endocrine therapy; p53; prognosis.

© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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Figures

Figure 1

Figure 1

Immunohistochemical examination of Ki-67 (a) and p53 (b) in invasive carcinoma. Representative results of positive staining are shown. Nuclear staining of Ki-67 (a) and p53 (b) can be observed in breast cancer cells.

Figure 2

Figure 2

Immunohistochemical examination of p53 in various cancer cell lines using formalin-fixed, paraffin-embedded cell block materials. Representative results are shown. Negative or only weak staining in a few cells is observed in H1299 p53 null cells and in H2228, Lovo, Hela and MCF-7 cells that do not have the TP53 gene mutation (upper panel), whereas nuclear staining can be observed in all cells in T47D, SK-BR-3, BT-474, MDA-MB-231 and MDA-MB-468 cells that have missense mutations of the TP53 gene (lower panel).

Figure 3

Figure 3

Disease-free survival according to expression of Ki-67 (a), p53 (b) and combination subgroups of Ki-67 and p53 (c) in estrogen-positive breast cancer patients treated with aromatase inhibitors as adjuvant endocrine therapy.

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