Clinical Significance of p53 Overexpression in Terms of Prognosis and the Efficacy of Chemotherapy According to the Breast Cancer Subtypes

Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue and Nobuyuki Arima

Department of Breast Oncology, Kumamoto Shinto General Hospital, Japan Department of Pathology, Kumamoto Shinto General Hospital, Japan

^*Correspondance to: Reiki Nishimura 

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Abstract:

Background: The p53 tumor suppressor gene is important for cell cycle regulation and DNA repair. TP53 mutation can be detected by Immunohistochemistry (IHC) because of the prolonged stability of the p53 protein. The aim of this study was to evaluate the clinical significance of p53 protein status in terms of the Disease-Free Survival (DFS) rates and the efficacy of adjuvant chemotherapy (anthracycline +/- taxane) according to the breast cancer subtypes. Methods: Primary invasive breast cancer patients (N=4,463) were enrolled in this retrospective study from January 2002 to December 2018. The IHC data (ER/PgR, HER2 and Ki-67) was used to determine the breast cancer subtypes. The Kaplan-Meier procedure and the log-rank test were used to calculate and analyze DFS. Univariate and multivariate analyses of the factors for DFS were performed using Cox's proportional hazard model. Results: Eight hundred and eight (18.1%) out of 4,463 cases had p53 overexpression. A significant correlation was seen between the p53 overexpression and ER/PgR negativity, HER2 positivity, higher Ki-67 values, a higher nuclear grade, positive nodes and larger tumors. Moreover, a higher rate of p53 overexpression was significantly associated with HER2 and Triple Negative (TN) type cancers. A multivariate analysis found that p53 was a significant factor for DFS in only the luminal A/B types. Chemotherapy was not effective in improving DFS in relation to the p53 status in luminal A/B and HER2 types. However, TN type patients with p53 overexpression had a slightly worse DFS in cases that did not receive chemotherapy. Moreover, there was no difference in DFS in cases that received chemotherapy. Conclusion: Luminal A/B subtypes with p53 overexpression had a higher grade of malignancy and a more unfavorable prognosis. However, the findings revealed that patients with TN subtype and p53 overexpression in adjuvant settings may benefit from chemotherapy.

Keywords:

Breast cancer; Chemotherapy; Disease-free survival; ki-67; p53 overexpression; Subtype

Cite the Article:

Nishimura R, Osako T, Okumura Y, Nakano M, Fujisue M, Arima N. Clinical Significance of p53 Overexpression in Terms of Prognosis and the Efficacy of Chemotherapy According to the Breast Cancer Subtypes. Clin Oncol. 2020; 5: 1696.