Journal
BMC MEDICINE
Volume 13, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12916-015-0392-6
Keywords
Breast cancer; Annexin A1; BRCA1 and BRCA2 mutations
Categories
Funding
- Cancer Research UK [C1287/A10118, C1287/A12014, C490/A10124, C490/A10119, C490/A16561]
- UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge
- BIHR Biomedical Research Centre at the University of Cambridge
- Dutch Cancer Society [NKI 2007-3839, 2009-4363, DDHK 2004-3124, DDHK 2009-4318]
- Baden Wurttemberg Ministry of Science, Research and Arts, Helsinki University Central Hospital Research Fund, Academy of Finland [266528]
- Finnish Cancer Society
- Nordic Cancer Union
- Sigrid Juselius Foundation
- Special Government Funding (FVO) of Kuopio University Hospital grants
- Cancer Fund of North Savo
- Finnish Cancer Organizations
- Australia National Breast Cancer Foundation
- National Health and Medical Research Council (NHMRC)
- Queensland Cancer Fund
- Cancer Foundation of Western Australia
- NIH [CA128978, CA116167, CA176785]
- NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]
- Breast Cancer Research Foundation
- David F and Margaret T Grohne Family Foundation
- Ting Tsung and Wei Fong Chao Foundation
- Intramural Research Funds of the National Cancer Institute
- Department of Health and Human Services, USA
- CAPES Foundation
- National Breast Cancer Foundation Practitioner Fellowship
- Cancer Council of New South Wales
- Cancer Council of Victoria
- Cancer Council of Tasmania
- Cancer Council of South Australia
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Ali] Funding Source: researchfish
- Cancer Foundation Finland sr [140146] Funding Source: researchfish
- Cancer Research UK [16561, 16563] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06, PRAC-13-04] Funding Source: researchfish
- National Institute for Health Research [CL-2013-14-006] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
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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.
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