whole brain   radiotherapy ( wbrt ) continues to represent 
 an important palliative treatment option for patients with brain metastases 
 from breast cancer . however , 
 many patients have active extracranial disease and eventually die from 
 extracranial cancer progression . within the last decade , several important new 
 treatment options for metastatic breast cancer became available , for example , 
 trastuzumab , taxane - based chemotherapy , capecitabine , and more effective 
 aromatase inhibitors . therefore , the possibility exists that more effective 
 systemic treatment might lead to improved survival also in the subgroup of 
 patients harbouring brain metastases . in order to examine this hypothesis , a 
 matched pairs analysis was performed that involved one group of patients , which 
 were treated after these new drugs were introduced , and one group of patients , 
 which were treated approximately 10 years earlier . the contemporary group 
 included all patients with brain metastases from breast cancer , which received 
 wbrt with 10 fractions of 3 gy between 2000 and 2007 at the university hospital 
 of north - norway . the patients ( n = 32 ) were identified from the database of the 
 radiation oncology facility . no patients with carcinomatous meningitis were 
 included . a 
 historical control group treated with the same wbrt regimen between 1987 and 1997 
 was generated . from this larger group ( n = 47 ) , patients were selected for a 
 matched pairs analysis without survival information available at the time of 
 matching . to obtain two groups with comparable baseline characteristics , two 
 matching criteria were used : prognostic class according to the published 
 recursive partitioning analysis ( rpa class ) [ 3 , 4 ] and the use of additional 
 local treatment for relapses after wbrt , for example , radiosurgery ( rs ) or 
 surgical resection . information on primary tumour features , such as hormone 
 receptor status and her2 receptor status , was not available in the historical 
 group . kruskal - wallis tests were used to compare the baseline 
 characteristics between the two groups . table 1 shows the patient 
 characteristics for the contemporary group and the matched group of 32 
 historical patients . as can be seen , the groups were balanced for the 
 established prognostic factors . more patients in the contemporary group had 
 received chemotherapy before diagnosis of brain metastases . time to development 
 of brain metastases was significantly longer . the fact that more patients in 
 the historical group were recorded to have had single brain metastases apparently 
 was not related to increased use of magnetic resonance imaging in recent years . the majority of patients in 
 the contemporary group were lymph node positive , hormone receptor negative , and 
 her-2 positive . neither hormone receptor status nor her-2 status was statistically 
 significant prognostic factor in this group ( p > .3 ) . only 4 patients 
 had not received systemic treatment , 2 had received endocrine treatment only , 
 and 26 had received chemotherapy before development of brain metastases ( 5 
 patients had 3 different lines of chemotherapy ) . twelve patients remained 
 without systemic treatment after wbrt , 5 received endocrine treatment only , 11 
 one line of chemotherapy , and 4 at least 2 lines of chemotherapy . as this was a 
 matching criterion , 3 patients in each group received rs or surgical resection 
 for progressive brain metastases . as a striking difference , only 8 patients in 
 the historical group received additional chemotherapy after wbrt ( endocrine 
 treatment unfortunately was not recorded ) . in the contemporary group , 60% 
 of the patients achieved at least a partial remission of their brain metastases 
 based on imaging after wbrt ( reduction in largest diameter of each lesion by at 
 least 50% without development of new lesions ) . at 6 months after wbrt , 59% of 
 the patients were progression - free in the central nervous system . median survival from first 
 diagnosis of breast cancer was 102 months in contemporary patients with initial 
 t1/2 n0 disease and 47.5 months in patients with more advanced disease ( p < .05 ) . table 2 demonstrates that the recent survival improvement from the 
 start of wbrt is entirely derived from rpa class ii patients , while no obvious progress 
 was achieved in rpa class iii . analysis of class i was not meaningful , as this 
 group included only 2 patients . only 2 of the contemporary patients in rpa 
 class iii received chemotherapy after wbrt ( versus one patient in the 
 historical group ) . patients without active treatment after wbrt had a median 
 survival of 3.5 versus 3.2 months , that is , no improvement over time . for 
 patients with active treatment , median survival also remained stable ( 9.0 versus 
 7.9 months ) , while the 1-year survival rate improved from 25 to 43% . the small 
 group ( n = 6 ) of patients that received the most aggressive treatment , defined as 
 trastuzumab - containing regimens and/or brain salvage treatment , had a median 
 survival of 15.4 months ( 4 patients survived > 1 year ) . this matched pairs analysis 
 was performed with two groups of patients , which received identical local treatment 
 for their brain metastases and were well balanced for the known prognostic 
 factors age , kps , extracranial disease status , graded prognostic assessment 
 ( gpa ) group , and rpa class . unlike the newly developed gpa , rpa class has been confirmed 
 as prognostic factor in patients with primary breast cancer in several studies 
 ( table 3 ) . in order to obtain enough historical patients for the matching 
 procedure , the treatment period was extended back to the year 1987 . the 
 recently suggested prognostic factor lymphopenia [ 5 , 6 ] has not been routinely 
 assessed in our department and could , therefore , not be included . a further 
 point that needs to be mentioned is the lack of information on hormone receptor 
 status , her-2 status , and endocrine treatment in the historical patient group , 
 which was treated before 1998 . thus , imbalances regarding these parameters , 
 which might have influenced the survival results to some degree , can not be 
 ruled out . as demonstrated in table 4 , the prognostic impact of hormone 
 receptor and her-2 status is difficult to interpret at this time , as the 
 published studies reported inconsistent results and are all limited in size . none 
 of the patients in the historical group received trastuzumab , taxanes , 
 capecitabine , or new - generation aromatase inhibitors . the first interesting finding 
 was that the interval from initial breast cancer treatment to brain metastases 
 has increased by 18 months , that is , 53% . median interval was longer than 
 previously reported in the literature ( table 3 ) . accordingly , increased overall 
 survival from first diagnosis of breast cancer was evident , in particular in 
 patients with initial t1/2 n0 disease . such results might be explained by a 
 change in the biology of the disease . however , the numbers of patients with 
 node - positive disease , receptor - negative disease , and her-2 positive disease 
 between 2001 and 2007 argues against this explanation . especially her-2 
 overexpression and hormone receptor negativity appear to influence the risk of 
 brain metastases development . in fact , the data favour changes in 
 treatment regimens as a more likely explanation . the use of systemic 
 chemotherapy has increased over time , both before and after the diagnosis of 
 brain metastases . however , such treatment was performed nearly exclusively in 
 those patients with brain metastases that belonged to the prognostically more 
 favourable groups ( better rpa class ) . whether changes in systemic treatment are 
 the only explanation for the marked survival improvement in rpa class ii in the 
 present study is difficult to assess . it is , for example , possible that more patients that previously 
 would have been assigned to rpa class i would now be assigned to class ii , 
 based on better methods for detection of extracranial metastatic disease . in 
 addition , rpa class ii is a quite inhomogeneous group of patients with large 
 potential differences , for example , in extent of cns involvement and kps . in the present analysis , it has improved in prognostically better patients and especially patients that 
 received active treatment , where the 1-year survival rates have almost doubled . 
 as these patient groups were small , confirmation of the results in other series 
 should be attempted . when looking at the literature , the series that is best 
 comparable to our own contemporary patients is the one reported by le scodan et 
 al . , which provides almost identical survival data ( table 3 ) . the series 
 that included the oldest data ( back to 1984 ) , is very close to our own 
 historical group . confirmed that patients without systemic 
 treatment have significantly poorer median survival ( 5 months versus 10 months 
 in patients with systemic treatment ) . these authors also found that 
 intensified local therapy of brain metastases improved the outcome . confirmed the value of both intensified local and systemic treatment in a 
 series of 198 patients . other nonrandomized series suggest that rs might 
 lead to better local control and survival than that reported from wbrt series . the impact of chemotherapy on brain control is less clear , although recent 
 data suggest that capecitabine might be able to induce remission of central 
 nervous system metastases from breast cancer . taken together , the present 
 results and the literature overview are compatible with the hypothesis that 
 improved systemic therapy might contribute to longer survival in patients with 
 brain metastases from breast cancer , which qualify for active systemic therapy 
 in addition to upfront wbrt .
newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases . in order to examine this hypothesis , 
 a matched pairs analysis was performed that involved one group of patients , which were treated after these new drugs were introduced , and one group of patients , which were treated approximately 10 years earlier . 
 the two groups were well balanced for the known prognostic factors age , kps , extracranial disease status , and recursive partitioning analysis class , as well as for the extent of brain treatment . 
 the results show that the use of systemic chemotherapy has increased over time , both before and after the diagnosis of brain metastases . 
 however , such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups . 
 survival after whole - brain radiotherapy has remained unchanged in patients without further active treatment . 
 it has improved in prognostically better patients and especially patients that received active treatment , where the 1-year survival rates have almost doubled . as these patient groups were small , confirmation of the results in other series should be attempted . 
 nevertheless , the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer .