Background: Triple-negative breast cancer (TNBC) amounts to approximately 15% of all breast cancer and is defined as lacking expression of oestrogen- and progesterone receptors (ER and PgR) and HER2 leaving chemotherapy as the only treatment option. The aggressive nature of TNBC is reflected by high histological grade, early onset of relapses, and more commonly visceral metastases. Further exploration of biological features in this group could (would) help to find potential targeted therapies. Aim: To compare intratumoural levels of VEGF and survival in patients with TNBC compared with HER2 positive patients and ER and/or PgR positive but HER2 negative patients. Patients and methods: 210 premenopausal patients with lymph-node negative breast cancer included in a prospective clinical trial were studied. (Ref Malmström et al JCO 19:2010-2019, 2001). Levels of VEGF were determined by an enzyme-linked immuno-sorbent assay (ELISA) on lysates from freshly frozen breast tumor material. HER2 amplification was determined by in situ hybridization of tumor with Her2 + or 3+ reactivity with IHC (determined by IHC followed by confirmatory FISH in 2+ or 3+). Results: Thirty-six out of 210 (17%) patients were classified as having a TNBC. The median level of VEGF in the total patient population was 81 ng/mg total protein (range 2.0- 3610). Significantly higher VEGF levels were found in TNBC compared with HER2 pos. or HER2 neg. ER/PgR pos. patients; median levels 250, 157 and 53 ng/mg total protein respectively (p<0.001). Similarly, 84% of TNBC had VEGF above the median compared to 62% in HER2 pos and 41% in the HER2 neg. ER/PgR pos. group (p<0.001). TNBC was significantly associated to high histological grade (89% grade III) (p<0.001), and high S-phase fraction (p=0.001). The highest rate of distant metastases was (seen or) recorded for HER2 pos patients while TNBC and HER2 neg. ER/PgR pos. had similar relapse rates (p<0.001; three-group comparison). After adjustment for chemotherapy, patients with TNBC survived significantly shorter after relapse compared with ER/PgR pos/HER2 neg patients (HR=7.2;95%CI=2.1-25; p=0.002) but not compared to HER2 pos patients (HR=2.3;95%CI=0.73-7.0; p=0.16). Conclusion: We here for the first time show significant higher levels of an angiogenesis stimulating factor, VEGF in TNBC. Whether blockade of angiogenesis can be an effective new targeted treatment option for this poor prognosis group will be elucidated in ongoing trials.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1077.
- ©2009 American Association for Cancer Research.