Purpose : Breast Cancer (BC) is a genetic, heterogeneous disease and has a remarkable variability according to racial factors. Hypothetic explanations for these disparities include differences in tumor biology. The present study was designed to compare clinical and pathological features between Peruvian Latinas and Spanish women with BC; interest of this analysis increases if we take into account the relationship among historic ancestries of both ethnic groups (Incas emporium and Spanish conquers). Methods : Information was retrospectively reviewed from patients files and pathologic reports from Instituto Nacional de Enfermedades Neoplasicas (INEN) in Lima- Peru, and Hospital Universitario 12 de Octubre in Madrid- Spain. In order to produce comparative information and avoid subjective clinical measurements we selected only non-metastatic and non-bilateral invasive BC cases that underwent surgery as initial therapy. BC cases were classified as molecular subtypes: Luminal A [RE+ and/or RP+, HER2−], Lum B [RE+ and/or RP+, HER2+], triple negative (TN) [RE-, RP-, HER2−] and HER2 [RE-, RP-, HER2+]. Variables were compared with the X2 test and survival curves were evaluated with Kaplan-Meier method. Results: The study included 3765 BC cases. The Spanish cohort involved 1539 (40.9%) women consecutively diagnosed between 1997 and 2007 (median follow-up of 7.9 years). The Peruvian cohort involved 2226 (59.1%) women consecutively diagnosed between 2000 and 2006 (median follow-up of 6.3 years). In terms of pathological features, grade I tumors were more frequent in Spanish (16.2%) than Peruvian women (9.6%) (p<0.001). Higher rates of lobular histology were also found in Spanish (12.5%) than Peruvian (6.0%) women (p<0.001). Spanish cases presented at earlier stages when evaluated by lymph node status (N0 in 58.9% vs 47.1%) (p<0.001) or by tumor size (T1 in 37.9% vs 17-2%). Conservative surgery were more frequent among Spanish cases (50.6% vs 16.8%) (p<0.001). TN molecular subtype were more frequent among Peruvian cases (22.5% vs 12.4%) (p<0.001). Brain (10.4% vs5.3%), and skin and subcutaneous (7.1% vs 2.4%) metastases were more frequently found in Peruvian patients. On the other hand, contralateral breast cancer was more frequent among Spanish patients (12.2% vs 2.8%). And when evaluated by molecular subtypes, bone metastases in TN were more frequent among Spanish (25.4%) than Peruvian (18.5%) cases. Disease-free survival rates at 7 years were similar between Spanish and Peruvian patients (80,3% vs 79,6%, p=0.197). However, overall survival at 7 years was better in Spanish women (90.4% vs 82.6%, p<0.001). Conclusion : Epidemiologic differences in terms of histological features, clinical stage at diagnosis, molecular subtypes distribution, recurrence patterns and prognosis were found among Spanish and Peruvian BC patients in this retrospective analysis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-09.

Background: Phenotype plays an important role in BC biology and outcome. We evaluated the characteristics and outcomes of clinical stages I-III BC patients with recurrence according to the IHC phenotype: ER or PR+/HER2-; HER2+ (regardless the ER and PR status) and triple negative (ER-/PR-/HER2-), to determine the influence of phenotype in the SNC recurrence. Methods: We reviewed 1,232 clinical stage I-III BC treated at INEN (2000-2002). Phenotypes were categorized by IHC into [ER+ and/or PR+, HER2-], [ER-, PR-, HER2-] and [HER2+ (regardless ER/PR status)]. Patients were classified in 3 risk groups (recursive partitioning analysis [RPA]; Gaspar et al. Int J Radiat Oncol Biol Phys 1997;37:745) according to 4 criteria: those with Karnofsky Performance Status (KPS) less than 70 (Class III), those with a KPS of or more, aged less than 65, with a controlled primary, no other systemic metastases (Class I), all other patients (Class II). We used Kaplan-Meier estimates for comparing CNS-free metastases survival and survival after CNS recurrence according to IHC phenotype or classes. Results: A median follow-up of 7.6 years; 416 (33.8%) patients had local, regional or distant disease dissemination, and 454 (36.9%) deaths were registered. In total, 62 (5.0%) patients developed CNS metastases (60 cases of cerebral and 2 of meningeal metastases), 36 (2.9%) of whom had developed CNS metastases as the site of first recurrence. 12 (2.1%), 31 (7.7%) and 19 (7.5%) were ER or PR+/HER2-, HER2+ and triple negative, respectively. CNS metastases free survival shown significant differences between ER or PR+/HER2-, HER2+ and Triple negative (97.3%, 89.6% y 90.5%, respectively; P<0.001). Main multivariate predictive factor was IHC phenotype (P<0.001), using [ER or PR+/HER2-] as reference, other phenotypes were expressed by hazard ratios (HR); [HER2+] (HR=3.8, 95%CI; 1.9 - 7.4), triple-negative (HR=4.0, 95%CI; 1.9-8.4). In regard to the RPA groups, 3 (4.9%) were class I, 28 (45.9%) class II and 30 (49.2%) class III. Median survival after CNS recurrence was 12.9, 6.1 and 2.8 for RPA Class I,II and III, respectively]; however there was not significant differences (p=0.085). In the multivariate analysis for OS after SNC metastases, only phenotype was significant and Triple Negative have the higher risk (HR=2.064; IC95% 0.94 — 4.531; P=0.023), Risk groups have not significant effect (P=0.088). Phenotype and outcome Conclusion: IHC phenotype is a strong risk factor for outcome; triple negative, and Class III breast cancer patients present a shorter time to CNS recurrence and survival after CNS recurrence than other IHC phenotypes and other risk groups. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-02.

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Background: TNBC is characterized by the lack of hormonal receptors and HER2 expression and occurs most frequently in Black and Hispanic than in Caucasian population. We compare clinicopathological and outcome variables between TNBC and non-TNBC Hispanic patients (pts). Methods: We reviewed 1044 cases of operable breast cancer treated at INEN, Lima-Perú (2000 — 2002). Phenotypes were categorized by IHC into TNBC and non-TNBC. Variables in both groups were compared with the X2 test. We used Kaplan-Meier method for comparing disease free survival (DFS), overall survival (OS), post recurrence survival by phenotype (TNBC v non-TNBC) and the hazard rate (HR) for different times. Results: 212 pts (20.3%) were TNBC and 832 non-TNBC (79.7%); median for age was 48 and 49 years (y), for tumor size 3.5 and 2.9cm; TNBC was more likely to have involved nodes (55.7 v 45.6%; P=0.009), tumors > 5cm (14.2 v 8.1%; P=0.011) and histological grade 3 (62.7 v 29.0%; P<0.001). Recurrence rates (RR) were 25.9 v 22.5% (TNBC v non-TNBC). TNBC and non-TNBC present different RR. Recurrence sites and phenotype Median of follow-up was 7.63 and 7.57y; there was not significant differences for DFS between TNBC and non-TNBC (72.8 v 76.6%;P=0.057), but in OS had differences (73.2 v 79.9%; P=0.014). The HR for recurrence was calculated to 1y (7.9 v 2.7%); 2y (8.8 v 5.8%); 3y (8.0 v 6.5%); 4y (2.7 v 3.3%) and to 5y (3.5 v 3.9%) and the HR for death to 1y (4.3 v 0.8%); 2y (6.7 v 2.6%); 3y (8.4 v 3.8%); 4y (5.5 v 2.8%) and to 5y (2.6 v 4.5%) for TNBC and non-TNBC, respectively. HR for recurrence and death was higher in TNBC until the first 3y and 4y, respectively, then HR were similar for both groups. Post recurrence survival show differences between TNBC and non-TNBC (HR=1.7; 95% IC 1.2 - 2.3; P=0.002). Conclusion: In early breast cancer, TNBC is more aggressive than non-TNBC; present a higher RR in brain, distant nodes and other soft tissues; strongly time-dependent HR for recurrence and death, and a worse Post recurrence survival. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-18.