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Trastuzumab-treated advanced breast cancer patients and brain metastases: just a little alert
Recently, some authors reported the high frequency of localizations to the central nervous system (CNS) in HER-2-positive breast cancer patients [1]. There are three hypotheses to explain such phenomenon: (i) these patients have a poorer prognosis and their disease has a more aggressive behavior with a much higher tropism for the CNS; (ii) trastuzumab can optimally control disease outside the blood–brain barrier but this antibody does not cross it; and (iii) trastuzumab prolongs survival of patients and so we can appreciate also brain metastases, frequently a late manifestation of disease.In our little series with 12 of 52 (23%) HER-2-positive patients developing CNS involvement during or after treatment with trastuzumab, there is not a prolongation of survival to justify the onset of brain metastases: half patients had their CNS localizations within only 16 months from the beginning of trastuzumab for metastatic disease. On the other hand, we may emphasize the fact that endocranial metastases often develop in presence of disease control in other body sites obtained with the antibody (8 of 12 cases were complete or partial responses in our series).
In conclusion, our alert is that we must pay attention to HER-2-positive trastuzumab-treated patients with periodical computed tomographic imaging of the brain and treat CNS metastases with adequate, and when indicated, aggressive measures because of a possible prolongation [2] of survival (continuation of trastuzumab associated with a different cytostatic agent + whole-brain or stereotactic radiotherapy ± surgery). All but three patients are alive in our series with >31 months survival in a case from the diagnosis of cerebral involvement.
Whether the high frequency of brain metastases is merely related to the aggressiveness of HER-2-positive disease, often associated with other unfavorable biologic parameters (estrogen receptor negativity, poor differentiation, and high proliferative index) or has other explanations, remains a challenge for researchers [3], like the need for a preventive approach (mostly for the patients in the adjuvant setting).
Department of Oncology, Ospedale Macerata, Via Santa Lucia 2, 62100 Macerata, Italy
(E-mail: umberto57{at}comeg.it)
References
1. Lai R, Dang CT, Malkin MG, Abrey LE. The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma. Cancer (2004) 101:810–816.[CrossRef][Web of Science][Medline]
2. Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol (2005) 23:2114–2116.
3. Gori S, Rimondini S, De Angelis V, et al. Central nervous system metastases in HER-2-positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist (2007) 12:766–773.
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  I. H. Park, J. Ro, K. S. Lee, B. H. Nam, Y. Kwon, and K. H. Shin Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer Ann. Onc., January 1, 2009; 20(1): 56 - 62. [Abstract] [Full Text] [PDF]
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