Abstract

Abstract Breast cancer is a heterogenous disease. The inferior prognosis of the triple-negative phenotype was primarily shown in studies, examining outcome by intrinsic subtype, determined via gene expression profiling. Several population based studies, determining the subtype via immunohistochemistry illustrated an analogous result. However in many of these studies a comparison of the triple-negative cohort with the non-triple negative cohort, including all subtypes of invasive breast cancer, was done. Data comparing the triple negative with the triple positive subgroup are limited. Purpose: To determine patients characteristics and prognostic significance of triple negative breast cancers in comparison to triple positive breast cancers as defined by immunohistochemistry. Patients and Methods: A database of 3346 primarily not metastasized, invasive breast cancer patients, diagnosed between 1998 and 2008, in whom all 3 markers (estrogen receptor, progesterone receptor and Her2/neu) were available, was reviewed. 197 patients (5,9 %) had triple negative phenotype, 91 (2,7 %) triple positive phenotype. Patients were treated by surgery (either mastectomy or breast conserving), followed by radiation therapy; a small subset of patients received IORT. Systemic therapy was given according to standard protocols used during the mentioned 10 year interval. Determination of ER and PR status was done by immunohistochemistry. Her2/neu status was obtained using the Hercep Test (DAKO). Hercep Test Scores of 2+ were additionally tested by fluorescent in situ hybridisation (FISH). Results: Median follow-up time was 47,9 months in the triple negative and 51,4 months in the triple positive cohort. Triple negative breast cancer patients experienced a significantly reduced 3-year total relapse-free survival (82,7 % vs. 93,4 %, p=0,019), 10-year local breast relapse-free survival (92,9 % vs. 97,8 %, p=0,036) and breast-cancer related overall survival (89,7 % vs. 100 %, p=0,002 at 3 years; 85,7% vs. 92,3%, p=0,041 at 10 years). Median survival time to progression and consequently to death was significantly reduced in this cohort (13,9 months vs. 32,1 months, p=0,023 and 8,7 months vs. 39,5 months respectively, p=0,006). In a model adjusted for known prognostic variables triple negative breast cancers were at significantly higher risk for total relapse (HR 4,081, 95 % CI 1,538-10,828, P<0,0001), local relapse (HR 3,139; 95 % CI 0,374-26,325, p=0,031) and death (2,173, 95 % CI 0,612-7,715, p=0,001). The prognostic effect of triple negative breast cancer on 10 year overall survival and 10 year total relaps-free survival was independent of nodal status, grade and the application of systemic therapy. Conclusions: In comparison with triple positive breast cancer patients those classified as triple negative have a poorer prognosis even under omission of adjuvant trastuzumab treatment (70,3 % of the triple positive patients failed to receive adjuvant trastuzumab in our study) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-03.

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