Original Article

International Journal of Clinical Oncology

, Volume 16, Issue 6, pp 694-700

First online:

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 HayashiAffiliated withDepartment of Breast and Endocrine Surgery, Faculty of Life Sciences, Kumamoto University Graduate School of Medical SciencesDepartment of Breast and Endocrine Surgery, Kumamoto City Hospital
  • , Yasuhiro OkumuraAffiliated withDepartment of Breast and Endocrine Surgery, Kumamoto City Hospital
  • , Tomofumi OsakoAffiliated withDepartment of Breast and Endocrine Surgery, Kumamoto City Hospital
  • , Yasuo ToyozumiAffiliated withDepartment of Clinical Pathology, Kumamoto City Hospital
  • , Nobuyuki ArimaAffiliated withDepartment of Clinical Pathology, Kumamoto City Hospital
  • , Hirotaka IwaseAffiliated withDepartment of Breast and Endocrine Surgery, Faculty of Life Sciences, Kumamoto University Graduate School of Medical Sciences
  • , Reiki NishimuraAffiliated withDepartment of Breast and Endocrine Surgery, Kumamoto City Hospital Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

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