Clinical Utility of Continuing Trastuzumab Beyond Brain Progression in HER-2–Positive Metastatic Breast Cancer

Abstract

In a previous issue of The Oncologist, Gori et al. [1] described well the patterns of progression and survival of human epidermal growth factor receptor (HER)-2–positive metastatic breast cancer (MBC) patients who develop central nervous system (CNS) metastases following treatment with trastuzumab-based therapies. Their results are consistent with previous findings reporting a higher-than-usual incidence of CNS metastases in patients treated with trastuzumab-including regimens [2, 3]. As highlighted by those authors, this phenomenon reflects the poor penetration of trastuzumab through the blood–brain barrier [4] rather than a loss of sensitivity to the treatment. In fact, most of the patients who develop CNS metastases on trastuzumab do so at a time when their extracranial disease is being controlled by trastuzumab itself [1–3]. For this reason, the longer survival observed in HER-2–positive MBC patients with CNS metastases has been attributed to the better control of extracranial disease obtained by trastuzumab [1, 5]. In this context, another issue that remains to be addressed is whether continuation of trastuzumab beyond brain progression would be beneficial for patients who develop CNS metastases while on treatment with trastuzumab, as compared with those individuals who crossover to second-line chemotherapy without trastuzumab. To address this question, we recently reviewed the medical records of the Division of Medical Oncology A at the Regina Elena National Cancer Institute in Rome in order to identify the HER-2–positive MBC patients who developed CNS metastases during treatment with trastuzumab either alone or in combination with chemotherapy and/or hormonal therapy. Figure 1 shows the flowchart of brain events and patterns of treatment of the 69 patients analyzed. Among the 20 patients who received further systemic treatment upon brain progression, 10 received further trastuzumab-based therapy and 10 received second-line chemotherapy without trastuzumab. Table 1 lists patient