Abstract
Purpose: Targeted therapy directed against HER2 has improved the outcome of patients with HER2-positive metastatic breast cancer in prospective clinical trials. No data are available how anti-HER2-therapy has influenced survival of unselected patients with HER2-positive metastatic breast cancer who receive treatment in routine care. Methods: Data of 118 subsequent patients with HER2-positive metastatic breast cancer who were treated in a community-based oncology group practice between 1995 and 2010 were analyzed retrospectively. Results: Median age at initial diagnosis of metastasis was 58 years (33-92). Twenty-two percent were metastasized at diagnosis of breast cancer, seventy-eight percent developed metastases in the course of the disease. Distribution of metastatic sites at initial diagnosis of metastasis was: 23% bone, 58% visceral, 5% CNS, 10% lymph nodes, 4% other. Hormone receptor was positive in 68% and negative in 31%. Palliative treatment consisted of antihormonal therapy in 56%, chemotherapy in 90% and radiotherapy in 50%. Seventy-five percent received anti-HER2-therapy consisting of trastuzumab in 80% and lapatinib in 1%, 19% received trastuzumab + lapatinib sequentially. Twenty-five percent received no anti-HER2-therapy. Median overall survival since initial diagnosis of metastasis was 34 months (0-277+). Conclusion: It could be shown that, compared to historical controls, targeted therapy against HER2 prolongs overall survival of patients with HER2-positive metastatic breast cancer who receive treatment in routine care.
Highlights
HER2 is a 185 kd transmembrane tyrosine kinase which is overexpressed in 15-18% of primary breast cancer cases (Slamon et al, 1987; Dendukuri, Khetani, McIsaac, & Brophy, 2007)
HER2-overexpression confers a negative prognosis with an increased relapse rate and reduced overall survival in primary breast cancer
Due to the aggressiveness of the tumour, HER2-positive metastatic breast cancer has a significantly shorter median Overall Survival (OS) of 18-20 months compared to HER2-negative disease with a median survival of 24-30 months (Slamon et al, 1987; Smith, 2001; Slamon et al, 2001; Marty et al, 2005)
Summary
HER2 is a 185 kd transmembrane tyrosine kinase which is overexpressed in 15-18% of primary breast cancer cases (Slamon et al, 1987; Dendukuri, Khetani, McIsaac, & Brophy, 2007). Within the pivotal trial first line therapy with trastuzumab prolonged overall survival in combination with anthracycline- or paclitaxel-chemotherapy from 20.3 to 25.1 months compared to chemotherapy alone in HER2-positive metastatic breast cancer (Slamon et al, 2001). Lapatinib is a dual HER1 and HER2 tyrosine kinase inhibitor, which in combination with capecitabine has shown activity in trastuzumab-refractory HER2-positive metastatic breast cancer and brain metastases (Geyer et al, 2006; Lin et al, 2008). No data are available so far how anti-HER2-therapy might influence overall survival in unselected patients with HER2-positive breast cancer who receive treatment outside clinical trials in routine care. This was the reason for us to ask the question whether anti-HER2-therapy leads to a prolongation of life in unselected patients with metastatic HER2-positive breast cancer who received routine care treatment in a community based oncology practice in Germany?
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