Abstract P3-08-62: An evaluation of p53 overexpression as a predictor of prognosis and chemotherapy benefit in relation to subtypes in primary invasive breast cancer
Authors: Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue, Nobuyuki Arima
Journal: Cancer Research (2020)

Abstract Background: The p53 tumor suppressor gene is important for cell cycle regulation and DNA repair. Somatic p53 gene mutations are associated with poor prognosis. Mutations in the p53 gene result in prolonged stability of the protein that can be detected by immunohistochemical (IHC) techniques. The impact of p53 protein status was investigated using the disease-free survival (DFS) rates and the efficacy of adjuvant chemotherapy (anthracycline+/-taxane) in relation to breast cancer subtypes. Methods: Primary invasive breast cancer patients who underwent treatment from January 2002 to December 2018 were enrolled in this retrospective study. A total of 4463 primary breast cancer cases were analyzed. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression (cutoff point: 50%), and the Ki-67 index value (cutoff point: 20%). Breast cancer subtypes were categorized based on the IHC data derived from ER/PgR, HER2 and Ki-67 values in invasive tumors. DFS was calculated using the Kaplan-Meier method and evaluated using the log-rank test. Cox's proportional hazard model was used to perform univariate and multivariate analyses of the factors related to DFS. Median follow-up period was 85 months. Results: 1. p53 overexpression rate was 18.1% (n=808) in all of the cases. The p53 overexpression significantly correlated with ER/PgR negativity, HER2 positivity, higher Ki-67 index values and nuclear grade, positive nodes and larger tumors. Patients with p53 overexpression received chemotherapy more often than those without overexpression in adjuvant settings. HER2 type and triple negative (TN) type had significantly higher rates of p53 overexpression, but luminal A and B types had lower p53 overexpression rates. 2. Patients with p53 overexpression had significantly worse DFS in luminal A and B types. However, p53 overexpression was not predictive for DFS in HER2 enriched, luminal HER2 and TN types. Multivariate analysis revealed that p53 was a significant factor for DFS in luminal A/B types. 3. The efficacy of chemotherapy for DFS was investigated according to the subtypes and p53 status. Chemotherapy did not affect the DFS in relation to p53 status in luminal A/B and HER2 types. However, in the TN type, patients with p53 overexpression had marginally worse DFS in cases without chemotherapy. On the other hand, there was no difference in DFS in the cases with chemotherapy. These findings suggest that chemotherapy is effective in improving the DFS in TN cases with p53 overexpression. Conclusion: p53 overexpression correlated with a higher grade of malignancy and unfavorable prognosis in patients with Luminal A/B subtypes. Although p53 status did not correlate with the prognosis in HER2 and TN subtypes, patients with p53 overexpression may benefit from chemotherapy in cases with TN subtype in adjuvant setting. Citation Format: Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue, Nobuyuki Arima. An evaluation of p53 overexpression as a predictor of prognosis and chemotherapy benefit in relation to subtypes in primary invasive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-62.