Time Dependent Improvement in Survival for Women with Multiple Brain Metastases from HER2 Positive Breast Cancer: The Influence of Systemic Therapy.

Abstract

Abstract Background: Women with multiple breast cancer brain metastases (BM) ineligible for neurosurgery or radiosurgery have a poor prognosis and the role of systemic therapy is ill defined.Method: The outcomes for 120 women treated for multiple (≥2) BM between 2002-2008 at this regional cancer centre have been analysed according to time of BM diagnosis (Cohorts (A) 2002-5 & (B) 2006-8) and HER2 status of the primary tumour (+ or -). We have previously shown that A+ patients experienced longer survival than A-, the advantage apparently restricted to a subgroup of A+ who continued trastuzumab after BM diagnosis (Church et al, Am J Clin Oncol 2008, 31(3) 250-4).Results: There was no difference in survival between B- and A- cohorts (B- patients (n=25) survival median 119 days; A- patients (n=53) median survival 118 days; p=0.57). In contrast there was a time dependent improvement in survival favouring B+ patients (n=19, median 520 days,) over A+ patients (n=23, median 148 days, p <0.02). B+ and A+ cohorts differed significantly in the consistency of their exposure to both trastuzumab (T) and chemotherapy (CT) post BM (p<0.02). Subsequently, patients in the B+ cohort was more frequently treated with additional lines of CT and 5 patients in the B+ cohort (versus none in A+) went on to receive second line anti-HER2 therapy (lapatinib).CohortT + CTLines of CT≥ 2LapatinibMedian survival12 month survivalA+ (n=23)39% (9pts)22% (5)0% (o)148 days30%B+ (n=19)79% (15pts)58% (11)26% (5)520 days80% p<0.02p<0.03p<0.02p<0.02 A+ and B+ were not significantly different with regard to presence of systemic metastases (SM) or time from SM to BM (median A+ 304 days; B+ 334, p=0.3)Conclusion: Following our earlier observation on the A+ cohort, the improvement in survival for B+ may reflect increased optimism of patients and physicians regarding the role of systemic therapy. Although no randomised trial has been performed, it is increasingly apparent from these and other data that HER2+ patients with multiple BM benefit from continued incorporation of systemic therapy into clinical management strategies and, at variance with historic experience, survival > 1 year can now be expected. Randomised trials, specifically to identify the best agents to accompany anti-HER2 therapy, will be required to further extend this benefit. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5092.