J Breast Cancer.  2013 Dec;16(4):386-394. 10.4048/jbc.2013.16.4.386.

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

• Ahn SH
• Kim HJ
• Han W
• Cho J
• Gong G
• Jung KH
• Kim SB
• Son BH
• Lee JW

• KMID: 1976376
• DOI: http://doi.org/10.4048/jbc.2013.16.4.386

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.

Keyword

Breast neoplasms; Drug resistance; Tumor suppressor protein p53

MeSH Terms

Breast Neoplasms*
Breast*
Drug Resistance
Drug Therapy
Estrogens
Humans
Methods
Multivariate Analysis
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Retrospective Studies
Tumor Suppressor Protein p53
Estrogens
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Tumor Suppressor Protein p53

Figure

• 

  Figure 1 (A) Breast cancer-specific survival (BCSS) (left) and overall survival (OS) (right) according to p53 status in the overall series. Subgroup analyses (B) by tumor size: ≤2 cm vs. >2 cm (left, BCSS; right, OS); (C) by lymph node status: negative vs. positive (left, BCSS; right, OS). (A-E) p53 is significantly prognostic in all subgroups except in the subgroup with grade 3. (D) by grade: grade1 or 2 vs. grade 3 (left, BCSS; right, OS); and (E) by age: <35 years vs. 35 to 49 years vs. >50 years old (left, BCSS; right, OS). (A-E) p53 is significantly prognostic in all subgroups except in the subgroup with grade 3. (F) OS and BCSS according to p53 status by possible intrinsic subtypes only by three immunohistochemical markers showed that the prognostic role of p53 persists only for the luminal A (hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative; blue line) and luminal B (HR positive/HER2 positive; green line) subtype and not for the HER2 (HR negative/HER2 positive; gray line) or TN (HR negative/HER2 negative; red line) subtype. LA=luminal A; LB=luminal B; TN=triple negative.

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