Trastuzumab linked to CNS metastases in HER2-positive breast cancer
MedWire News: Treatment with trastuzumab is associated with an increased risk for central nervous system (CNS) metastases in patients with human epidermal growth factor receptor (HER)2-positive breast cancer, Italian researchers report.
This may, in part, be due to improvements in systemic control and overall survival associated with trastuzumab-based therapy that "leads to an 'unmasking' of CNS metastases that would otherwise remain clinically silent before a patient's death," say Antonio Musolino (University Hospital of Parma) and colleagues.
Recent reports have indicated a growing incidence of CNS metastases in patients with breast cancer, which have been associated with trastuzumab treatment, the researchers note in the journal Cancer.
To investigate this phenomenon, they evaluated incidence, survival, and risk factors for CNS metastases among breast cancer patients listed in the Parma Province Cancer Registry between 2004 and 2007.
Of 1458 patients with stage I to III invasive breast cancer, 1210 (83%) had HER2-negative disease and 219 (15%) patients had HER2-positive disease. HER2-status was not available for the remaining 29 (2%) patients.
After a median follow-up period of 4.1 years, a significantly higher proportion of HER2-positive patients had CNS metastases compared with HER2-negtive patients, at 5.0% versus 1.3% respectively.
Stratifying the HER2-positive patients by trastuzumab treatment status revealed that 1.6% of those never treated with the drug had CNS metastases compared with 10.5% of those who received trastuzumab as adjuvant therapy for metastatic disease.
According to multivariate analysis, adjusted for possible confounding factors, HER2-positive patients treated with trastuzumab had a 4.3-fold higher risk for CNS metastases than HER2-positive and negative patients who did not receive trastuzumab.
A high Ki-67 index and estrogen and progesterone receptor negativity were also independent risk factors for the development of CNS metastases.
Musolino and co-authors point out that trastuzumab does not penetrate the blood-brain barrier well, even in the presence of brain metastases.
"Consequently, the CNS is a potential sanctuary site in patients with HER2-positive disease treated with trastuzumab," they say.
The researchers conclude that further studies are needed "to investigate whether the early detection of CNS metastases in HER2-positive patients treated with trastuzumab improves outcomes, either by improving survival or by delaying or preventing the appearance of neurologic symptoms."
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By Laura Dean