Abstract P4-11-06: Population Based Outcomes after Whole Brain Radiotherapy in Patients with Metastatic Breast Cancer in the Pre and Post Trastuzumab Eras
Authors: Tyldesley S , Karam I , Nichol A , Woods R , Speers C , Kennecke H. 
Published: April 2011

Background: In the Pre-trastuzumab (Pre-T) era, survival rates after brain radiotherapy (RT) for breast cancer patients were 4 to 8 months. Trastuzumab (T) was approved and funded in British Columbia in the metastatic setting in 1999. We examined the survival of Her2-positive and negative metastatic breast cancer at a provincial level in the Pre-T and T eras after brain RT.

Material and Methods: All women with a diagnosis of breast cancer between 2000 and 2007 (T era) who were treated with brain RT in British Columbia were identified. A series of cases with brain metastasis from breast cancer treated with brain irradiation diagnosed between 1986 and 1992 with banked tissue on which Her-2 testing had been performed were also identified (Pre-T era). Date of death was determined from the tumour registry. Baseline prognostic factors were compared using Chi Square for categorical data, and t-test for continuous data. Survival was estimated using the Kaplan-Meier method, and comparisons between eras and between her-2 groups were done with a log-rank test. Variables significant for survival on log-rank test were entered into a Cox regression for multivariate analysis for each era separately.

Results: A total of 455 women with brain metastases from breast cancer were identified from the T era, and 131 were identified from the Pre-T era. The median age at diagnosis was 53 years in both eras. The percentage of cases with ER-positive (43% and 41% p=0.2) and Grade 3 tumours (74% and 67%, p=0.2) were not statistically different. The percentage of cases with Her2-positive disease were statistically different the two eras (29% in Pre-T and 46% in the T eras, p=&lt;0.001). Of the T era Her2-positive patients, 85% received T. The median time from diagnosis to brain RT was longer in the pre-T era (3.3 years versus 2.3 years, p&lt; 0.001). The most common prescription used for whole brain RT was 20 Gy in 5 fractions in both eras, however it was more common in the pre-T era (87%) compared to the T era (68%) (p=&lt;0.001). Although stereotactic radiotherapy, which first became available in our region in 1997, was occasionally used as a boost in BC, all but 15 (11%) of the pre-T era patients had died prior to its availability. Survival was longer after whole brain RT in the T era (1 year survival 27% versus 14%, log rank p=0.07). In the T era, one year survival was better for those with Her2 positive disease in the T era (39%) compared to those with Her2 negative disease (19%) in the T era (p-value &lt; 0.0001), and to those with Her 2 positive disease in the pre-T era (3%, P&lt;0.001). In the pre-T era, although 1 year survival was better (18%) for Her2 negative disease compared to Her2 positive disease (3%), the difference was not statistically significant (p=0.1). In a Cox model, RT dose and ER status were significant variables in both eras, but Her2 status and age were only significant variables in the T era (p all &lt; 0.001).

Discussion: For patients with Her2 negative disease, there was no difference in survival after RT for brain metastases between the Pre-T and T eras. However, for patients with Her2 positive disease, survival after RT for brain metastases has increased significantly in the trastuzumab era.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-06.