Annexin A1 expression in a pooled breast cancer series: Association with tumor subtypes and prognosis

Marcelo Sobral-Leite, Jelle Wesseling, Vincent T.H.B.M. Smit, Heli Nevanlinna, Martine H. van Miltenburg, Joyce Sanders, Ingrid Hofland, Fiona M. Blows, Penny Coulson, Gazinska Patrycja, Jan H.M. Schellens, Rainer Fagerholm, Päivi Heikkilä, Kristiina Aittomäki, Carl Blomqvist, Elena Provenzano, Hamid Raza Ali, Jonine Figueroa, Mark Sherman, Jolanta LissowskaArto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Kelly Phillips, kConFab/AOCS Investigators, Fergus J. Couch, Janet E. Olson, Celine Vachon, Daniel Visscher, Hermann Brenner, Katja Butterbach, Volker Arndt, Bernd Holleczek, Maartje J. Hooning, Antoinette Hollestelle, John W.M. Martens, Carolien H.M. van Deurzen, Bob van de Water, Annegien Broeks, Jenny Chang-Claude, Georgia Chenevix-Trench, Douglas F. Easton, Paul D.P. Pharoah, Montserrat García-Closas, Marjo de Graauw, Marjanka K. Schmidt

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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.

    Original languageEnglish
    Article number156
    Number of pages11
    JournalBMC Medicine
    Issue number1
    Publication statusPublished - 2 Jul 2015

    Bibliographical note

    This is an Open Access article distributed under the terms of the Creative Commons AttributionLicense (, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated


    • Annexin A1
    • BRCA1 and BRCA2 mutations
    • Breast cancer


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