Lani
03-26-2006, 07:08 PM
Citation: European Journal of Cancer Supplements Volume 4, No. 2, March 2006, page 163
D.N. Church1, R. Modgil2, S. Guglani2, A. Bahl2, K. Hopkins2, J.P. Braybrooke1, C.G.A. Price1
1Bristol Haematology and Oncology Centre, Medical Oncology, Bristol, United Kingdom
2Bristol Haematology and Oncology Centre, Clinical Oncology, Bristol, United Kingdom
Aim: To assess survival of patients with brain metastases (BM) from HER2 positive metastatic breast cancer (MBC) treated with trastuzumab after diagnosis of BM.
Historical series indicate that symptomatic BM develop in 10–16% of patients with MBC, and are associated with a median survival of 3–6 months. The increased incidence of BM (28–43%) in patients receiving trastuzumab for HER2 positive disease is well recognised, but increasingly apparent is the favourable prognosis of such patients if trastuzumab is continued.
We have performed a retrospective review of 71 assessable patients treated at our institution who have received anti-neoplastic treatment for BM between May 2002 and April 2005. HER2 positivity was defined as 3+ on immunohistochemistry or positive on fluorescence in-situ hybridization (FISH).
The median survival after diagnosis of BM in patients in whom HER2 status was negative or unknown (n = 49) measured 3 months, with 8.1% (95% CI 3.2%-19.2%) of patients alive at 1 year; patients with HER2 positive disease who did not receive trastuzumab after diagnosis of BM (n = 8) had similar median (3 months) and 1 year (12.5%) survival. In contrast, the median survival of women with HER2 positive disease treated with trastuzumab after diagnosis of BM (n = 14) was significantly longer at 12 months (p = 0.002), with 57.1% (95% CI 32.6%-78.6%) alive at 1 year. Notable within this group are several patients with multiple BM who have displayed responses or prolonged stabilization of central nervous system (CNS) disease to systemic anti-neoplastic therapies added to trastuzumab.
Our experience confirms the favourable prognosis of patients with HER2 positive BM treated with trastuzumab after diagnosis of CNS metastases. While this improvement in survival may result from better control of systemic disease, another possibility is that trastuzumab may also have a beneficial effect on BM. Although trastuzumab does not cross the blood brain barrier (BBB) under physiological conditions and fails to accumulate in cerebrospinal fluid after intravenous administration, the disturbed BBB evident in BM may allow accumulation of sufficient concentrations within metastases to synergise with chemotherapy and radiotherapy, phenomena well demonstrated in preclinical work. Prospective confirmatory studies are required.
D.N. Church1, R. Modgil2, S. Guglani2, A. Bahl2, K. Hopkins2, J.P. Braybrooke1, C.G.A. Price1
1Bristol Haematology and Oncology Centre, Medical Oncology, Bristol, United Kingdom
2Bristol Haematology and Oncology Centre, Clinical Oncology, Bristol, United Kingdom
Aim: To assess survival of patients with brain metastases (BM) from HER2 positive metastatic breast cancer (MBC) treated with trastuzumab after diagnosis of BM.
Historical series indicate that symptomatic BM develop in 10–16% of patients with MBC, and are associated with a median survival of 3–6 months. The increased incidence of BM (28–43%) in patients receiving trastuzumab for HER2 positive disease is well recognised, but increasingly apparent is the favourable prognosis of such patients if trastuzumab is continued.
We have performed a retrospective review of 71 assessable patients treated at our institution who have received anti-neoplastic treatment for BM between May 2002 and April 2005. HER2 positivity was defined as 3+ on immunohistochemistry or positive on fluorescence in-situ hybridization (FISH).
The median survival after diagnosis of BM in patients in whom HER2 status was negative or unknown (n = 49) measured 3 months, with 8.1% (95% CI 3.2%-19.2%) of patients alive at 1 year; patients with HER2 positive disease who did not receive trastuzumab after diagnosis of BM (n = 8) had similar median (3 months) and 1 year (12.5%) survival. In contrast, the median survival of women with HER2 positive disease treated with trastuzumab after diagnosis of BM (n = 14) was significantly longer at 12 months (p = 0.002), with 57.1% (95% CI 32.6%-78.6%) alive at 1 year. Notable within this group are several patients with multiple BM who have displayed responses or prolonged stabilization of central nervous system (CNS) disease to systemic anti-neoplastic therapies added to trastuzumab.
Our experience confirms the favourable prognosis of patients with HER2 positive BM treated with trastuzumab after diagnosis of CNS metastases. While this improvement in survival may result from better control of systemic disease, another possibility is that trastuzumab may also have a beneficial effect on BM. Although trastuzumab does not cross the blood brain barrier (BBB) under physiological conditions and fails to accumulate in cerebrospinal fluid after intravenous administration, the disturbed BBB evident in BM may allow accumulation of sufficient concentrations within metastases to synergise with chemotherapy and radiotherapy, phenomena well demonstrated in preclinical work. Prospective confirmatory studies are required.