TNBC exhibits a more aggressive clinical course than non-TNBC. This point is illustrated in a population-based study from the California Cancer Registry, which involved 51,074 women with primary breast cancer [ 8 ]. TNBCs were present at a more advanced stage and were associated with shorter 5-year survival times than non-TNBC phenotypes (77 vs. 93%). Moreover, withineach disease stage at diagnosis, TNBC was consistently associated with poorer survival than non-TNBC (Fig.8 [ 1 ) ]. When compared with other breast cancer subtypes in the pre-trastuzumab era, TNBC was associated with outcomes worse than those for the luminal subtypes and similar to that for the HER2-overexpressing subtype. In a follow-up analysis of the California Cancer Registry, which included61,309 women, the 5-year survival rates were 96% among women with ER positive, PR positive, HER2 negative breast cancer and 76% among women with TNBC or the HER2overexpressing subtype 16 . Comparable Þndings were also reported in other studies , [ , 17 ]. Notably, the 7 , 9 , 1 12 poorer outcome in patients with TNBC is observed despite comparable responses to cytotoxic chemotherapy, [ ]. 18 19TNBC often presents as advanced-stage disease. In a study of 1,34 patients with invasive breast cancer, the ageadjusted odds ratio (OR) for advanced disease stage at *15% of all diagnosis was signiÞcantly higher in patients with TNBC breast cancers 10 TNBC is characterized by an than in patients with luminal type A (OR, 2.2; 95% con5 [ ]. Ð aggressive clinical course and poor survival and,unlikeinterval [CI], 1.0Ð4.9) [ ]. Studies have also shown Þdence 7 tumors overexpressing hormone receptors or HER2, is not unlike with most breast cancer subtypes, there is a that, amenable to hormone therapy or HER2-directed agents lack of correlation between tumor size and lymph node such as trastuzumab , Ð 13]. These factors highlight 8 , [11 9 , positivity among TNBC cases1 [ 20 , 21 ]. Most TNBCsthe need for new treatment options for patients with TNBC. of high histologic grade, with frequencies of grade 3 are Here we describe the clinical characteristics of TNBC and histology across TNBC cohorts ranging from 6 to 91% [ 7 , provide an overview of targeted agents under development 9 , 1 , 17 , 2 ]. Grade 1 histology is uncommon, although it for this aggressive phenotype. has been detectedin up to 10% of patients with TNBC [ ]. Most TNBCs are ductal carcinomas of no special 1 type, but some cases may have features of metaplastic DeÞnition of TNBC carcinomas and medullary cancers9 , [ Ð 25 ]. On 23 As mentioned above, TNBC is characterized by a lack of 100 expression (or minimal expression) of estrogen receptor (ER) and progesterone receptor (PR) as well as an absence 80 of HER2overexpression. According to guidelines pub60 lished by the American Society of Clinical Oncology (ASCO), ER/PR negativity by immunohistochemical (IHC) 40 TNBC Stage I analysis is deÞned as% of tumor cell nuclei immuno\1 TNBC Stage II TNBC Stage III-IV reactive for ER or PR [ 14 ], although clinical trials of Other Breast Cancers Stage I 20 patients with TNBC may allow the enrollment of patients OtherBreast Cancers Stage II Other Breast Cancers Stage III-IV with B10% expression. Non-overexpression of HER2 0 (HER2 negative or equivocal) is deÞned in the ASCO 0 10 20 30 40 50 Months guidelines as IHC B2? for HER2 or a ßuorescence in situ hybridization ratio of \2.2 (HER2 to CEP17) or average Fig. 1 Comparison of overall survial by disease stage for women HER2 gene copy number of fewer than 6signals per with triple negative breast cancer (TNBC) and those with other 15 ]. nucleus without an internal control probe [ phenotypes adapted from Bauer et al. [ 8]
Percent 5-Year Survival
Breast Cancer Res Treat
*5% of all breast cancers, with higher rates of BRCA1-related breast cance occurring among patients of Ashkenazi Jewish decent [ 35]. The BRCA1 protein plays a role...