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HER2 Codon 655 G-Allele Is Associated With Reductions in Plasma High-Density Lipoprotein Levels in Breast Cancer Patients Treated With Tamoxifen
  1. Nai-Wen Chang, PhD*,
  2. Dar-Ren Chen, MD,
  3. Fei-Na Chen, PhD,
  4. Chingju Lin, PhD§,
  5. Chen-Teng Wu, MD, MS
  1. From the *Department of Biochemistry, China Medical University, Taichung; †Department of Surgery, Changhua Christian Hospital, Changhua; Departments of ‡Social Medicine and §Physiology, China Medical University, Taichung; and ∥Department of Surgery, Fong-Yuan Hospital, Taichung County, Taiwan, ROC.
  1. Received June 10, 2011, and in revised form August 3, 2011.
  2. Accepted for publication August 29, 2011.
  3. Reprints: Chen-Teng Wu, MD, MS, Department of Surgery, Fong-Yuan Hospital, No. 100 An-Kan Rd, Fong-Yuan City, Taichung County 420, Taiwan, ROC. E-mail: biom1236{at}
  4. Drs. Lin and Wu equally contributed to this study.
  5. Supported by research grants from the China Medical University (CMU97-095 and CMU96-231), the Taiwan Department of Health, China Medical University Hospital Cancer Research of Excellence (DOH100-TD-C-111-005), and the Taiwan Central Region Hospital Alliance, Department of Health, Executive Yuan (9908).
  6. The authors declare that they do not hold any financial and personal relationships with other people or organization that could inappropriately influence this work.


Background Retrospective studies have revealed that overexpression of the epidermal growth factor receptor ErbB-2 (HER2) reduced the efficacy of tamoxifen therapy, which is associated with an increased risk for cardiovascular events. The aim of this study was to evaluate the effects of the HER2 I655V polymorphism (ATC/isoleucine to GTC/valine) on lipid profiles after tamoxifen treatment.

Methods Thirty-four women diagnosed with breast cancer were recruited in the study and followed up for 6 months. The presence of the HER2 I655V polymorphism and fasting plasma lipid profiles before and after tamoxifen treatment were determined for each subject for the duration of the study.

Results In response to tamoxifen therapy, we found that plasma total cholesterol (TC, P = 0.041), low-density lipoprotein-cholesterol (LDL-C, P < 0.001), and high-density lipoprotein-cholesterol (HDL-C, P = 0.012) levels decreased significantly in the A-allele (AA genotype) carriers compared with the baseline measurements. Plasma LDL-C (P < 0.001) and HDL-C (P < 0.001) levels decreased significantly, and the TC/HDL-C (P = 0.027) ratio increased significantly in the G-allele (AG/GG genotypes) carriers. According to the repeated-measures analysis, G-allele carriers had a lower ratio of LDL-C/HDL-C than A-allele carriers did (P = 0.016). Notably, G-allele carriers had a greater reduction in HDL-C concentration than A-allele carriers (P = 0.039; G-allele, −12.4 ± 6.8 mg/dL vs A-allele, −5.6 ± 9.5 mg/dL).

Conclusions This study shows that the HER2 codon 655 G-allele was associated with a larger reduction in plasma HDL-C levels in breast cancer patients under tamoxifen therapy. Therefore, we suggest that the polymorphism of HER2 655 codon should be considered for the prevention of cardiovascular events in breast cancer patients after tamoxifen therapy.

Key Words
  • HER2 I655V polymorphism
  • tamoxifen
  • HDL-cholesterol
  • breast cancer

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