Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study

BACKGROUND: A series of retrospective studies have reported that patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer are at a greater risk of central nervous system (CNS) metastases. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk. METHODS: The authors evaluated incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry over the 4-year period between 2004 and 2007. RESULTS: A total of 1458 patients with a diagnosis of stage I to III invasive breast cancer were analyzed for study purposes. At a median follow-up of 4.1 years, CNS events were observed in 1.3% and 5% of HER2-negative patients and HER2-positive patients, respectively (P < .0001). The administration of trastuzumab either as adjuvant therapy or for metastatic disease was associated with a significantly increased risk of CNS involvement at first disease recurrence and after first extracranial recurrence, respectively. According to multivariate analysis, HER2-positive status and trastuzumab treatment, high Ki-67 index, and hormone receptor negativity remained independent risk factors for the development of CNS metastasis. CONCLUSIONS: To the authors' knowledge, this is the first population-based cancer registry study analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The data from the current study provide evidence that patients with HER2-positive breast cancer have a significantly higher incidence of CNS metastasis after treatment with trastuzumab. Improvements in systemic control and overall survival associated with trastuzumab-based therapy may lead to an "unmasking" of CNS disease recurrence that would otherwise remain clinically silent before a patient's death.