Breast Cancer Research and Treatment

, Volume 132, Issue 3, pp 947–953 | Cite as

MDM2 SNP309 and TP53 R72P associated with severe and febrile neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide

  • Masatsugu Okishiro
  • Seung Jin Kim
  • Ryo Tsunashima
  • Takahiro Nakayama
  • Kenzo Shimazu
  • Atsushi Shimomura
  • Naomi Maruyama
  • Yasuhiro Tamaki
  • Shinzaburo Noguchi
Preclinical Study


The aim of this study was to investigate the association of two genetic polymorphisms, MDM2 SNP309 and TP53 R72P, with incidence of neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide (FEC). Primary breast cancer patients (n = 216) treated with adjuvant FEC (60, 75 or 100 mg/m2) were included in this study. The association of genotypes of MDM2 SNP309 and TP53 R72P, determined by TaqMan SNP Genotyping Assays, with febrile neutropenia (FN) was investigated. In the patients treated with FEC100, G/G genotype for MDM2 SNP309 (G/G genotype MDM2 ) was significantly (P < 0.01) associated with a lower incidence (5.3 vs. 39.2%) of severe neutropenia (<100/mm3) than with T/T + T/G genotypes MDM2 , and C/C genotype for TP53 R72P (C/C genotype TP53 ) was significantly (P = 0.03) associated with a higher incidence (58.3 vs. 27.3%) of FN than with G/G + G/C genotypes TP53 . The combination of C/C genotype TP53 and T/T + T/G genotype MDM2 showed the highest risk for developing severe neutropenia (83.3%) and FN (62.5%) than any other combinations. In the patients treated with FEC60 or FEC75, there was no significant association of MDM2 SNP309 and TP53 R72P with severe neutropenia and FN. MDM2 SNP309 and TP53 R72P are significantly associated with severe neutropenia and FN, respectively, in breast cancer patients treated with FEC100, and especially their combination may be a useful predictor of severe neutropenia and FN.


Breast cancer FEC100 MDM2 SNP309 Neutropenia TP53 R72P 



This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

S. Noguchi has received research grants and honoraria from Pfizer.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Masatsugu Okishiro
    • 1
  • Seung Jin Kim
    • 1
  • Ryo Tsunashima
    • 1
  • Takahiro Nakayama
    • 1
  • Kenzo Shimazu
    • 1
  • Atsushi Shimomura
    • 1
  • Naomi Maruyama
    • 1
  • Yasuhiro Tamaki
    • 1
  • Shinzaburo Noguchi
    • 1
  1. 1.Department of Breast and Endocrine SurgeryOsaka University Graduate School of MedicineSuita City, OsakaJapan

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