Effect Modification of Hormonal Therapy by p53 Status in Invasive Breast Cancer.
10.4048/jbc.2013.16.4.386
- Author:
Sei Hyun AHN
1
;
Hwa Jung KIM
;
Wonshik HAN
;
Jihyoung CHO
;
Gyungyub GONG
;
Kyung Hae JUNG
;
Sung Bae KIM
;
Byung Ho SON
;
Jong Won LEE
Author Information
1. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. asanbreastcenter@gmail.com
- Publication Type:Original Article
- Keywords:
Breast neoplasms;
Drug resistance;
Tumor suppressor protein p53
- MeSH:
Breast Neoplasms*;
Breast*;
Drug Resistance;
Drug Therapy;
Estrogens;
Humans;
Methods;
Multivariate Analysis;
Receptor, Epidermal Growth Factor;
Receptors, Progesterone;
Retrospective Studies;
Tumor Suppressor Protein p53
- From:Journal of Breast Cancer
2013;16(4):386-394
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: We aimed to confirm the prognostic and predictive value of p53 expression, particularly in invasive breast cancer patients, according to immunohistochemical hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. METHODS: Immunohistochemical data for p53, estrogen receptor, progesterone receptor, and HER2 expression from a total of 15,598 patients were retrospectively retrieved from the web-based database of the Korean Breast Cancer Society. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated and compared using the Kaplan-Meier method and log-rank test, respectively. Multivariate analyses were performed using a stratified Cox proportional hazard regression model. A model evaluating interactions between p53 expression and both hormonal therapy and chemotherapy was used to determine the treatment benefit from both modalities. RESULTS: The prognostic value of p53 for OS and BCSS was most significant in the HR+/HER2- subgroup, with hazard ratios of 1.44 (95% confidence interval [CI], 1.08-1.93) and 1.47 (95% CI, 1.09-1.99), respectively. The p53 overexpression hazard ratios were of borderline significance for the HR+/HER2+ subgroup and were not significant for the HR-/HER2+ and HR-/HER2- subgroups. The model with interaction terms revealed that hormonal therapy significantly interacts with p53 status (p=0.002 and p=0.007 for OS and BCSS, respectively), suggesting an insignificant prognostic value for p53 status (p=0.268 and p=0.296 for OS and BCSS, respectively). An interaction between chemotherapy and p53 status was not found in this model. CONCLUSION: p53 overexpression has independent prognostic value, particularly in cases of HR+/HER2- invasive breast cancer, which may be due to effect modification of hormonal therapy dependent on p53 status.
