Effect Modification of Hormonal Therapy by p53 Status in Invasive Breast Cancer.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sei Hyun
SH
Ahn
Department of Biostatistics and Clinical Epidemiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hwa Jung
HJ
Kim
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Wonshik
W
Han
Department of Surgery, Keimyung University School of Medicine, Daegu, Korea.
Jihyoung
J
Cho
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Gyungyub
G
Gong
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kyung Hae
KH
Jung
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sung-Bae
SB
Kim
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Byung Ho
BH
Son
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jong Won
JW
Lee
Breast neoplasms; Drug resistance; Tumor suppressor protein p53