International Journal of Clinical Oncology

, Volume 16, Issue 6, pp 694–700 | Cite as

Time to first tumor progression as a predictor of efficacy of continued treatment with trastuzumab beyond progression in human epidermal growth factor receptor 2-positive metastatic breast cancer

  • Mitsuhiro Hayashi
  • Yasuhiro Okumura
  • Tomofumi Osako
  • Yasuo Toyozumi
  • Nobuyuki Arima
  • Hirotaka Iwase
  • Reiki Nishimura
Original Article



Trastuzumab demonstrates significant clinical benefits in HER2-positive metastatic breast cancer (MBC), and recent clinical trials suggest that trastuzumab should be continued in combination with other chemotherapy beyond progression. There is an urgent need to assess if patients could substantially benefit from continuing trastuzumab-based therapy.


We reviewed 91 patients with HER2-positive MBC treated with trastuzumab and investigated correlations between survival and clinical response to first trastuzumab-based therapy and biological markers, time to first tumor progression (1st TTP), response rate (RR), estrogen receptor (ER), Ki-67, and p53 overexpression.


With a median follow-up of 33 months, 76 patients had received two or more lines of consecutive trastuzumab-based therapy. Median 1st TTP was 8.6 months; patients who received trastuzumab with chemotherapy had a longer 1st TTP and better RR than those without chemotherapy. In terms of survival after first progression, patients with a longer 1st TTP (≥8.6 months) had significantly better survival compared with those who had a shorter 1st TTP (24.3 months vs. 15.4 months, P = 0.024), and multivariate analysis revealed that 1st TTP was a significant prognostic factor (HR 0.44, 95% CI 0.23–0.82, P = 0.01). There were no correlations between survival and ER or Ki-67; however, there was a correlation with p53 overexpression (HR 1.92, 95% CI 1.01–3.64, P = 0.045).


1st TTP is a significant prognostic factor for patients who receive subsequent trastuzumab-based therapy. This factor should be considered when determining the efficacy of continuing trastuzumab or switching to another anti-HER2 therapy beyond progression.


Trastuzumab Time to progression Treatment beyond progression Human epidermal growth factor receptor 2 Metastatic breast cancer p53 overexpression 



We thank the staff of the Department of Clinical Pathology at Kumamoto City Hospital for their technical assistance.

Conflict of interest

H. Iwase received honoraria from Pfizer and research funding from Chugai-Roche and Novartis. The other authors report no conflict of interest.


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Copyright information

© Japan Society of Clinical Oncology 2011

Authors and Affiliations

  • Mitsuhiro Hayashi
    • 1
    • 2
  • Yasuhiro Okumura
    • 2
  • Tomofumi Osako
    • 2
  • Yasuo Toyozumi
    • 3
  • Nobuyuki Arima
    • 3
  • Hirotaka Iwase
    • 1
  • Reiki Nishimura
    • 2
  1. 1.Department of Breast and Endocrine Surgery, Faculty of Life SciencesKumamoto University Graduate School of Medical SciencesKumamotoJapan
  2. 2.Department of Breast and Endocrine SurgeryKumamoto City HospitalKumamotoJapan
  3. 3.Department of Clinical PathologyKumamoto City HospitalKumamoto-cityJapan

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