Heterogeneity of Triple Negative Breast Cancer (TNBC): TNBC Might Be Divided into Two or More Subgroups by Clinicopathologic Findings.
Authors: Park Y. , Chang M. , Lee S. , Kim S. , Cho E. , Choi Y. , Ok O. , Baek H. , Lee J. , Nam S. , Yang J. , Ahn J. , Im Y. 
Published: December 2010

Background: Breast cancer comprises a heterogeneous group of diseases that vary in morphology, biology, behavior and response to therapy. Triple-negative breast cancer (TNBC) is a subtype of tumors (estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor-2 (HER2) receptor negative) with aggressive clinical behavior which currently lacks effective targeted therapies. TNBC exhibits a distinct pattern of recurrence which is characterized by rapidly rising rate in the first 2 years following diagnosis, a peak at 2-3 years followed by a decline in recurrence risk over the next 5 years. However, some of the TNBC patients show indolent clinical behavior associated with good clinical outcome. This reinforces the notion that TNBC is a heterogeneous group comprising subtypes with different features and clinical outcome. The aim of this study is to classify TNBC into two subgroups at least, each of which has different clinical course and long-term outcome.Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of patients with recurred or metastatic TNBC who received palliative treatment from 1999 to 2007 at Samsung Medical Center.Results: One hundred and seventy-three patients with recurrent and/or metastatic TNBC, who were available clinical data, were recognized. Of 173 patients, the number of relapsed patients after curative surgery was 154, and remaining were initially metastatic patients. The median relapse-free survival (RFS) of 154 patients was 23.6 months (95% CI, 20.4-26.8) and the median overall survival from metastasis of all 173 patients was 21.2 months (95% CI, 16.4-26.0). We divided the patients into two groups according to RFS of 36 months. TNM staging did not show any relationship with RFS (median RFS 24, 27, and 21 months for each stage, p=0.135). The TNBC patients who had RFS of 36 months or greater showed better disease control rate (DCR), progression-free survival (PFS) to 1st line palliative chemotherapy and overall survival (OS) than those with RFS of less than 3 years (DCR 55% vs 77%, p=0.022; median PFS 3.6 vs 7.7 months, p=0.0001; median OS 17.4 vs 42.0 months, p=0.0003). The incidence of brain metastases at the time of first metastasis was much more common in patients with shorter RFS than in those with longer RFS (16% vs 3%, p=0.047). Cox-regression multivariate analysis for OS revealed presence of brain metastasis, presence of hepatic metastasis, and RFS of less than 3 years were identified as independent risk factors (HR 2.01, p=0.007 for brain metastasis; HR 1.99, p=0.007 for hepatic metastasis; HR 2.45, p=0.001 for RFS of 3 year or greater). The results of immunohistochemical staining for basal-maker were pending.Conclusion:TNBC may be classified into two subgroups by RFS. The patients who have RFS of 3 year or greater showed significantly better DCR, PFS to palliative chemotherapy and OS than those who have RFS of less than 3 years. Different therapeutic strategies should be considered for each subgroup.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6032.