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
A part of this work was presented at the American Society of Clinical Oncology 2010 Breast Cancer Symposium in Washington,
DC, on October 1–3, 2010.