Abstract
<h3>Background</h3> HER2-positive breast cancer accounts for approximately 20% of all cases of breast cancer and has an aggressive metastatic course due to distinct natural history. Brain metastasis is diagnosed in up to 40% of patients with HER2-positive breast cancer and is associated with substantial morbidity and mortality. We aimed to investigate the incidence of brain metastases in patients with HER2-positive breast cancer treated at our institute. <h3>Methods</h3> Between 1995 and 2009, 513 women with pathologically confirmed HER2-positive breast cancer were identified with the hospital information system. Median age was 45years (range 20–75years). The patients' AJCC stages were: stage I (7%), stage II (58%) and stage III (35%). Histological sub-types were: infiltrating ductal carcinoma (96%), infiltrating lobular carcinoma (2%), and others (2%). Pathological grades were: grade I/II (41%) and grade III (59%). 70% of patients were treated with primary surgery. Chemotherapy regimens were: doxorubicin and taxane-based therapy (75%), doxorubicin-based therapy (5%), CMF (9%), and other regimens (5%), either in a neoadjuvant or adjuvant setting. Only 6% of the patients received trastuzumab therapy. 5% of the patients did not receive any type of chemotherapy or targeted therapy. Post-operative radiotherapy was delivered to 86% of patients. Incidence and median time to brain metastases were determined. <h3>Findings</h3> Median follow-up duration was 48months. Patterns of failure were: local (5%), regional (2%), and distant metastases (26%). 14% of patients with distant metastases who did not respond to treatment were found to have brain metastases as first site of relapse. Overall brain metastases were seen in 25% of the patients. Median time to brain metastases was 13months (range 8–50). <h3>Interpretation</h3> Our results suggest that the HER2-positive breast cancer sub-type remains more aggressive and is associated with a very high incidence of brain metastases. Future studies should focus on new therapeutic options, such as small molecule tyrosine kinase inhibitors in adjuvant settings, to decrease the incidence of systemic relapse.
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