Abstract P5-07-07: Prognostic value of mutant TP53 in basal breast cancer

Abstract

Abstract Backgrounds; p53 is a tumor suppressor gene that plays an important role in cell cycle control and apoptosis. In the breast cancer, mutant tumor protein (TP53) is expressed in approximately 30% and patients with mutant TP53 often tend to have poor response to chemotherapy and poor prognosis than those with normal TP53. But, according to a recent study, TP53 inactivation could cause to significant DNA damage and to eventual cell death by mitotic catastrophe. We investigated the expression frequency and prognostic value of mutant TP53 using tissue microarrays of 898 invasive breast cancers. Patients and methods; From January 1995 to December 2005 at Yeungnam university hospital, patients who diagnosed with the primary invasive breast cancer and received operation were included in this study. Patients with bilateral breast cancer or distant metastasis at the time of diagnosis were excluded. According to the immunohistochemical results of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), Ki67, epidermal growth factor (EGFR) and cytokeratin (CK) 5/6, we classified patients into 6 subgroups, luminal A, luminal B1, B2, HER2-enriched, normal breast-like (triple negative nonbasal) and basal-like breast cancers. Immunohistochemical staining for TP53 was performed and we defined more than 10% stain of tumor cell as mutant TP53-positive. Distribution and prognostic significance of mutant TP53 in each subgroup was investigated. Results; In 898 invasive breast cancers, mutant TP53 was identified in 33.5% (301/898). Each expression frequency of mutant TP53 was 10.9% (42/385) in luminal A, 32.1% (45/140) in luminal B1, 50.0% (34/68) in luminal B2, 63.7% (72/113) in HER2-enriched, 54.7% (35/64) in normal breast-like and 57.0% (73/128) in basal-like subtype, respectively. In whole breast cancer patients, patients with mutant TP53 tended to have poor overall survival (OS) and disease free survival (DFS). However, there was no statistical significance (p = 0.187 and p = 0.651). But, in 128 patients with basal-like breast cancer, mutant TP53 showed good prognosis in both OS and DFS (p = 0.003 and p = 0.021). In basal-like breast cancer, the expression of mutant TP53 had no association with other clinicopathologic factors such as tumor size, lymph node metastasis, histological grade, lymphovascular invasion etc. and 98.4% (126/128) patients received adjuvant chemotherapy. In multivariate anaylsis, expression of mutant TP53 was an independent prognostic factor for OS and DFS in basal-like breast cancers (p = 0.008 and p = 0.012). Conclusions: This study showed that basal-like breast cancer with mutant TP53 has a good outcome in both OS and DFS. Further studies are needed to identify the action mechanism of mutant TP53. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-07-07.