M Sobral-Leite, J Wesseling, VTHBM Smit, H Nevanlinna, MH van Miltenburg, J Sanders, I Hofland, FM Blows, P Coulson, G Patrycja, JHM Schellens, R Fagerholm, P Heikkilä, K Aittomäki, C Blomqvist, E Provenzano, HR Ali, J Figueroa, M Sherman, J Lissowska, A Mannermaa, V Kataja, V-M Kosma, JM Hartikainen, K-A Phillips, kConFab/AOCS Investigators, FJ Couch, JE Olson, C Vachon, D Visscher, H Brenner, K Butterbach, V Arndt, B Holleczek, MJ Hooning, A Hollestelle, JWM Martens, CHM van Deurzen, B van de Water, A Broeks, J Chang-Claude, G Chenevix-Trench, DF Easton, PDP Pharoah, M García-Closas, M de Graauw, MK Schmidt
BACKGROUND: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. METHODS: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. RESULTS: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45). CONCLUSIONS: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.