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.
BACKGROUND: A series of retrospective studies have reported that patients with humanepidermal 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 cancerpatients 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.
Authors: Kunal S Taskar; Vinay Rudraraju; Rajendar K Mittapalli; Ramakrishna Samala; Helen R Thorsheim; Julie Lockman; Brunilde Gril; Emily Hua; Diane Palmieri; Joseph W Polli; Stephen Castellino; Stephen D Rubin; Paul R Lockman; Patricia S Steeg; Quentin R Smith Journal: Pharm Res Date: 2011-10-20 Impact factor: 4.200
Authors: Taofeek K Owonikoko; Jack Arbiser; Amelia Zelnak; Hui-Kuo G Shu; Hyunsuk Shim; Adam M Robin; Steven N Kalkanis; Timothy G Whitsett; Bodour Salhia; Nhan L Tran; Timothy Ryken; Michael K Moore; Kathleen M Egan; Jeffrey J Olson Journal: Nat Rev Clin Oncol Date: 2014-02-25 Impact factor: 66.675
Authors: C Bachmann; E M Grischke; T Fehm; A Staebler; J Schittenhelm; D Wallwiener Journal: J Cancer Res Clin Oncol Date: 2012-12-06 Impact factor: 4.553