Early-stage Triple-negative Breast Cancer Patients Research Articles

258P - Prognostic Factors in Early-Stage Triple Negative Breast Cancer (TNBC): The Limits Of Clinical and Pathological Features

ABSTRACT Background Triple negative breast cancer (TNBC) patients (pts) is an heterogeneous population regarding prognostic. Therefore, clinical and histological features were evaluated in a large monocenter cohort of patients treated for localized TNBC to identify good-prognostic TNBC. Methods All consecutive early-stage TNBC (ER 0%, PR 0%, HER2 neg) patients treated at European Georges Pompidou Hospital, Paris, France, between 2000 and 2011 were included. Records were reviewed for demographic, clinical and pathological data. Prognostic factors were determined using univariate and multivariate stepwise log-rank analysis on disease-free survival (DFS) and overall survival (OS). Results This analysis included 128 women with early-stage TNBC. Clinical and histological characteristics are summarized below. After a median follow-up of 37 months 36 relapses and 19 deaths were observed. The 3-years recurrence rate was 30% (95%CI 22-40) in the whole population. For DFS, bad prognostic factors in univariate analysis were: large tumor size (T3-4), node involvement (N1-3), node capsular effraction, lymphovascular invasion (LVI) and high grade (SBR 2-3). Multivariate analysis identified tumor size (T3-4) (HR 3.70, 95%CI 1.61-8.52) and LVI (HR 2.87, 95%CI 1.39-5.93) as independent factors. The 3-years recurrence rate remained high (20%, 95%CI 10-34) in patients with two good prognostic factors (T0-2 and no LVI). For OS, bad prognostic factors significant in univariate and multivariate analysis were: node capsular effraction (HR 3.57, 95%CI 1.17-10.92) and LVI (HR 3.43, 95%CI 1.18-9.92). Conclusions In this early-stage TNBC series, LVI was a bad prognostic factor of relapse and death. However, the 3-years recurrence rate remained high in patients with good prognostic features. Therefore, new biomarkers are mandatory for a better stratification of this heterogeneous population. Clinical and histological characteristics N (128pts) % Median age (yrs) 56 range 22-88 Histological type Invasive ductal carcinoma 123 96 Invasive lobular carcinoma 5 4 Tumor stage T0-T2 105 82 T3-T4 23 18 Node stage N0 97 76 N1-3 31 24 Node capsular effraction pos 14 11 neg 111 87 NE 3 2 Tumor grade (SBR) 1 8 6 2-3 107 84 NE * 13 10 Lymphovascular invasion (LVI) pos 34 27 neg 74 58 NE ** 20 16 * Due to neoaduvant chemotherapy ** Due to small biopsies. Disclosure S. Haouas: Grant from Association pour la Recherche en Therapeutiques Innovantes en Cancerologie (ARTIC). All other authors have declared no conflicts of interest.

Correlation of Snail expression and survival in patients with early-stage triple-negative breast cancer (TNBC).

10525 Background: In breast and other cancers, tumors reactivate a developmental program, the epithelial-mesenchymal transition (EMT), to increase cell motility and facilitate invasion and metastasis. Snail is a transcription factor that has been implicated in triggering EMT. We hypothesized that Snail expression is an important mediator of invasion, metastasis, and decreased survival in breast cancer. Methods: We analyzed protein levels of Snail and EMT markers using reverse-phase protein arrays (RPPA) of 334 primary breast cancers from the frozen tumor bank at M. D. Anderson, obtained from patients with early-stage disease. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier product and compared among groups via the log-rank test. Multivariate analysis was conducted via Cox proportional hazards models. Results: 267 patients had complete clinical data. Median age was 61 (range 27-88). 84% had stage I-II disease, 16% stage III. 66% of tumors were hormone- receptor (HR) positive, 3% HER2-positive, 31% TN. Prognostic factors were similar in the low- and high-Snail groups. At a median follow-up of 30.3 months, there were 65 recurrences and 65 deaths. Among TNBC patients, in a univariate model, estimated RFS was marginally significantly worse in the high-Snail vs. the low-Snail group (hazard ratio [hr], 2.11; 95% CI = 0.91, 4.88; p = 0.082). This became significant after adjustment for age and stage in a multivariate model (hr, 2.44; 1.01,5.88; p = 0.047). Strikingly, Snail was a marker of early relapse in TNBC patients, with a 2-year relapse rate of 41% in high-Snail vs. 19% in low-Snail patients. RFS was not different between high- and low-Snail groups in the HR-positive subset (p = 0.737). For all patients, high Snail expression correlated with an increase in the mesenchymal marker fibronectin (p < 0.001, Fisher's exact), consistent with the occurrence of EMT in high- Snail tumors. Conclusions: Snail expression is correlated with decreased RFS, in particular early relapse at < 2 years, in early-stage TNBC patients. TNBC patients with high Snail expression may be candidates for therapy to prevent metastases, in the form of inhibitors of the Snail pathway or EMT. No significant financial relationships to disclose.