Trastuzumab-based regimes improved clinical outcome in women with overexpressing HER2 metastatic breast cancer, mainly due to the availability of different combination therapies, clinically active and well tolerated. In this study we retrospectively evaluated clinical activity and toxicity of trastuzuamb plus gemcitabine regimen in heavily pretreated HER2 positive metastatic breast cancer patients. Although the observed population was heavily pretreated, the evaluated regimen was notably effective in terms of response rate, time to progression and survival, with very mild toxicity. These data suggest that in over expressing HER2 metastatic breast cancer patients, sequential trastuzumab based chemotherapeutic regimens can achieve good response rate with prolonged TTP in responding patients, even after other target therapy such as lapatinib based combinations. 1. Introduction Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase which is crucial in cell growth and differentiation. The HER2 gene is amplified in 15–20% of human breast cancers, and this feature is a well-known poor prognostic factor [1–3]. Trastuzumab (Herceptin Roche, Basel, Switzerland), a humanised monoclonal antibody with specificity for HER2, changed the natural history of HER2 overexpressing breast cancer, in the adjuvant setting as well as in metastatic disease. After phase II studies, the results of important phase III randomized trial enabled the registration of regimen of weekly paclitaxel plus trastuzumab by Food and Drug Administration (FDA) for HER2-positive metastatic breast cancer (MBC) [4–7]. Although the combination of taxane with trastuzumab is considered the reference regimen for HER2 overexpressing MBC, other combination therapies were evaluated in extensive phase II trials [8]. In patients with progressive disease after first-line trastuzumab-based regimens, a current clinical practice is to continue trastuzumab changing the chemotherapeutic partner. Therefore, the identification of different combinations of trastuzumab-based regimens for sequential use is important. In a previous study, we tested efficacy and tolerability of trastuzumab plus vinorelbine (VNR) regimen in first- and second-line setting for HER2 overexpressing MBC, with value for response rate (RR) of 78%, median time to progression (TTP) of 9 months, and median overall survival (OS) of 28 mounths. Very mild toxicity was observed [9]. Our results were in agreement with those previously published [10–19]. They were recently confirmed in two prospective and randomized trials,
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