GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR Prognostic factors and survival according to tumor subtype in women presenting with breast cancer brain metastases at initial diagnosis. GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR ARGENTINA J.P. Leone1, A.O. Zwenger2, J. Iturbe2, J. Leone2, B.A. Leone2, C.T. Vallejo2 Background Results Breast cancer represents one of the most common causes of brain metastases. The occurrence of this event is a catastrophic complication of metastatic breast cancer, associated with poor prognosis, significant morbidity and reduced quality of life. Brain metastases generally occur as a late event in the natural course of breast cancer. The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is less common. There is a lack of data about patient characteristics and prognostic factors in this unique group of patients, which makes the prognostic assessment and management very challenging. A total of 740 patients were included in this study. Median age was 60 years (range 26-93). Median follow-up was 6 months (range 1-48). OS at 1 and 3 years were 44.6% and 20.7%, respectively. There were 471 deaths reported. At diagnosis, brain was the only site of metastasis in 125 patients, whereas 66.2% had metastases in bone, 33.2% in liver and 44.7% in lung. Among patients with known variables, 56.5% had grade III/IV tumors, 46.6% were HR+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% TNBC. Table 1 shows the patient characteristics according to tumor subtype. Patients with TNBC had higher tumor grade (p<0.0001), higher rates of brain only (p=0.001) and lung metastases (p=0.037), lower rate of bone metastases (p<0.0001) and were more likely to die from breast cancer (p<0.0001). Table 2. Univariate and Multivariate Analysis Variable Log-Rank P Cox P HR 95.0% CI for HR Lower Upper Age at diagnosis, y 0.0002   <50 years Reference 50-64 years 0.850 1.033 0.741 1.439 >64 years 0.001 1.840 1.276 2.653 Race 0.0041 White Black 0.051 1.397 0.999 1.953 Other (American Indian/AK Native, Asian/Pacific Islander) 0.937 1.020 0.631 1.649 Grade 0.0696 I II 0.131 1.626 0.865 3.057 III/IV 0.081 1.765 0.932 3.342 Histology 0.0145 Ductal Lobular 0.006 2.081 1.238 3.496 Mixed ductal and lobular 0.199 0.552 0.223 1.366 Mucinous 0.359 0.394 0.054 2.881 Carcinoma 0.435 1.181 0.777 1.795 Tumor subtype <0.0001 HR-positive/HER2-negative Triple negative 0.010 1.541 1.108 2.143 HR-positive/HER2-positive 0.059 0.685 0.462 1.014 HR-negative/HER2-positive 0.325 1.222 0.820 1.821 Sites of metastases Bone (Yes vs No) 0.1823 0.780 1.054 0.730 1.521 Liver (Yes vs No) 1.645 1.236 2.190 Lung (Yes vs No) 0.002 0.288 1.170 0.876 1.563 Brain only (Yes vs No) 0.1597 0.696 1.102 0.678 1.789 Marital status 0.0165 Single Married 0.047 0.715 0.513 0.996 Other (Separated/Divorced/Widowed) 0.546 0.898 0.633 1.273 Objective Analysis of OS for the entire cohort. Median OS 10 months. Table 1. Patient Characteristics The aim of this study was to analyze the influence of tumor subtype compared with other prognostic factors in the survival of patients who present with BMIBCD.   Tumor subtype: HR-positive/HER2-negative HR-positive/HER2-positive HR-negative/HER2-positive Triple negative Unknown* Total N % P All patients 293 39.6% 107 14.5% 89 12.0% 140 18.9% 111 15.0% 740 100.0% Age at diagnosis, y <50 54 18.4% 25 23.4% 26 29.2% 35 25.0% 9 8.1% 149 20.1% 0.005 50-64 125 42.7% 59 55.1% 44 49.4% 62 44.3% 48.6% 344 46.5% >64 114 38.9% 23 21.5% 19 21.3% 43 30.7% 48 43.2% 247 33.4% Race White 231 78.8% 78 72.9% 69.7% 105 75.0% 73 65.8% 549 74.2% 0.19 Black 46 15.7% 16 28 20.0% 33 29.7% 142 19.2% Other 15 5.1% 12 11.2% 8 9.0% 7 5.0% 5 4.5% 47 6.4% 1 .3% .9% 0.0% 2 Grade I 20 6.8% 3 2.1% 1.8% 3.5% <0.0001 II 112 38.2% 34 31.8% 22.5% 14.3% 22 19.8% 208 28.1% III/IV 30.4% 49 45.8% 53.9% 63.6% 29 26.1% 304 41.1% 72 24.6% 21 23.6% 58 52.3% 202 27.3% Histology Ductal 213 72.7% 92 86.0% 68 76.4% 113 80.7% 76 68.5% 562 75.9% 0.002 Lobular 9.9% 2.8% 1.1% 38 Ductal and lobular 6 2.0% 4.7% 2.2% 17 2.3% Mucinous 1.7% .7% Carcinoma 40 13.7% 5.6% 18 20.2% 32 28.8% 116 Bone metastases No 65 22.2% 36.0% 54.3% 246 33.2% Yes 224 76.5% 82 76.6% 55 61.8% 60 54.1% 483 65.3% 4 1.4% 2.7% 11 1.5% Liver metastases 198 67.6% 94 67.1% 61.3% 472 63.8% 0.012 28.0% 41 46.1% 42 30.0% 36 32.4% 235 13 4.4% 2.9% 6.3% Lung metastases 162 55.3% 60.7% 39 43.8% 66 47.1% 53 47.7% 385 52.0% 0.037 115 39.2% 32.7% 44.9% 70 50.0% 52 46.8% 312 42.2% 5.5% 6.5% 10 5.4% 5.8% Brain metastases only 249 85.0% 93 86.9% 80.9% 98 70.0% 80.2% 601 81.2% 0.001 13.0% 14 13.1% 28.6% 17.1% 16.9% 3.4% 1.9% Marital status at diagnosis Single 71 24.2% 26.2% 16.4% 169 22.8% 0.12 Married 118 40.3% 49.5% 37 41.6% 31.5% 305 41.2% 81 27.6% 37.1% 36.9% 225 7.8% 6.7% Status Alive 121 41.3% 57 53.3% 20.7% 30 27.0% 269 36.4% Dead 172 58.7% 50 46.7% 64.0% 79.3% 73.0% 471 Cause of Death Breast cancer 161 54.9% 106 75.7% 77 69.4% 447 60.4% 3.8% 3.6% 24 3.2% *Unknown patients are excluded from the comparative analysis Materials and Methods We obtained data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, using the 18 registry (1973-2013) database. We extracted all cases of women with brain metastases at the time of initial diagnosis of microscopically confirmed stage IV breast cancer diagnosed between 2010 and 2013. Patients with other primary neoplasms either before or after breast cancer were excluded. The following variables were analyzed: age at diagnosis, race, year of diagnosis, grade, histology, ER, PR, HER2, type of breast surgery, radiation therapy, laterality, marital status, site of metastases, survival months, vital status and cause of death. Patient characteristics were compared between tumor subtypes using chi2 or Fisher’s exact tests. Survival probabilities were estimated using the Kaplan Meier method. Log-Rank test analyzed differences in overall survival (OS) between groups. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. OS was shorter for patients with triple negative tumors (P=<0.0001). Conclusions Although the prognosis is generally poor, 20.7% of patients were still alive 3 years after diagnosis. There were substantial differences in OS according to tumor subtype. The HR+/HER2- group represented the largest proportion of cases. In addition to tumor subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Analysis of OS according to liver metastases showed significantly longer survival for patients with no liver involvement (P=<0.0001). 1University of Iowa Holden Comprehensive Cancer Center and Iowa City VA Medical Center, 2Grupo Oncológico Cooperativo del Sur, Argentina email: jose-leone@uiowa.edu