p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer - PubMed (original) (raw)

p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer

Hiroko Yamashita et al. Breast Cancer Res. 2006.

Abstract

Introduction: Endocrine therapy is the most important treatment option for women with hormone receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified.

Materials and methods: The expression of HER2, p53, and Ki67 was examined by immunohistochemistry in primary breast tumour specimens from 73 metastatic breast cancer patients who received first-line treatment with endocrine therapy on relapse, and analysed to determine whether expression of these molecular markers affected the response to endocrine therapy.

Results: Of the 73 invasive ductal carcinomas, 12.3%, 21.9%, and 35.6% were positive for HER2 overexpression, p53 protein accumulation, and Ki67 expression, respectively. All patients received endocrine therapy as first-line treatment for metastatic breast cancer; 34 patients (46.6%) responded. Patients with primary breast tumours that had p53 protein accumulation and Ki67 expression showed significantly more resistance to endocrine therapy (P = 0.0049 and P = 0.024, respectively). There were also tendencies for HER2 overexpression to correlate with resistance to endocrine therapy, but this did not reach significance. p53 protein accumulation and HER2 overexpression significantly reduced post-relapse survival (P < 0.0001 and P = 0.001, respectively), and these factors were also statistically significant in a multivariate analysis.

Conclusion: These data suggest that p53 protein accumulation is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in hormone receptor-positive metastatic breast cancer.

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Figures

Figure 1

Representative immunohistochemical staining of HER2, p53, and Ki67 in invasive ductal carcinoma. (a) Negative staining of HER2. (b) Positive staining of HER2. (c) Negative staining of p53. (d) Positive staining of p53. (e) Negative staining of Ki67. (f) Positive staining of Ki67.

Figure 2

Post-relapse survival according to HER2 overexpression, p53 protein accumulation, and Ki67 expression. (a) Post-relapse survival according to HER2 overexpression. (b) Post-relapse survival according to p53 protein accumulation. (c) Post-relapse survival according to Ki67. HER2 overexpression and p53 protein accumulation significantly reduced post-relapse survival.

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p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer - PubMed (original) (raw)