TY - JOUR
T1 - Annexin A1 expression in a pooled breast cancer series
T2 - Association with tumor subtypes and prognosis
AU - kConFab/AOCS Investigators
AU - Sobral-Leite, Marcelo
AU - Wesseling, Jelle
AU - Smit, Vincent T.H.B.M.
AU - Nevanlinna, Heli
AU - van Miltenburg, Martine H.
AU - Sanders, Joyce
AU - Hofland, Ingrid
AU - Blows, Fiona M.
AU - Coulson, Penny
AU - Patrycja, Gazinska
AU - Schellens, Jan H.M.
AU - Fagerholm, Rainer
AU - Heikkilä, Päivi
AU - Aittomäki, Kristiina
AU - Blomqvist, Carl
AU - Provenzano, Elena
AU - Ali, Hamid Raza
AU - Figueroa, Jonine
AU - Sherman, Mark
AU - Lissowska, Jolanta
AU - Mannermaa, Arto
AU - Kataja, Vesa
AU - Kosma, Veli Matti
AU - Hartikainen, Jaana M.
AU - Phillips, Kelly Anne
AU - Couch, Fergus J.
AU - Olson, Janet E.
AU - Vachon, Celine
AU - Visscher, Daniel
AU - Brenner, Hermann
AU - Butterbach, Katja
AU - Arndt, Volker
AU - Holleczek, Bernd
AU - Hooning, Maartje J.
AU - Hollestelle, Antoinette
AU - Martens, John W.M.
AU - van Deurzen, Carolien H.M.
AU - van de Water, Bob
AU - Broeks, Annegien
AU - Chang-Claude, Jenny
AU - Chenevix-Trench, Georgia
AU - Easton, Douglas F.
AU - Pharoah, Paul D.P.
AU - García-Closas, Montserrat
AU - de Graauw, Marjo
AU - Schmidt, Marjanka K.
AU - Aghmesheh, Morteza
AU - Amor, David
AU - Andrews, Lesley
AU - Antill, Yoland
AU - Armitage, Shane
AU - Arnold, Leanne
AU - Balleine, Rosemary
AU - Bankier, Agnes
AU - Bastick, Patti
AU - Beesley, Jonathan
AU - Beilby, John
AU - Bennett, Barbara
AU - Bennett, Ian
AU - Berry, Geoffrey
AU - Blackburn, Anneke
AU - Bogwitz, Michael
AU - Brennan, Meagan
AU - Brown, Melissa
AU - Buckley, Michael
AU - Burgess, Matthew
AU - Burke, Jo
AU - Butow, Phyllis
AU - Byron, Keith
AU - Callen, David
AU - Chauhan, Deepa
AU - Chauhan, Manisha
AU - Christian, Alice
AU - Clarke, Christine
AU - Colley, Alison
AU - Cotton, Dick
AU - Crook, Ashley
AU - Cui, James
AU - Culling, Bronwyn
AU - Cummings, Margaret
AU - de Fazio, Anna
AU - Delatycki, Martin
AU - Dickson, Rebecca
AU - Dixon, Joanne
AU - Dobrovic, Alexander
AU - Dudding, Tracy
AU - Edkins, Ted
AU - Edwards, Stacey
AU - Eisenbruch, Maurice
AU - Farshid, Gelareh
AU - Fawcett, Susan
AU - Fellows, Andrew
AU - Fenton, Georgina
AU - Field, Michael
AU - Firgaira, Frank
AU - Flanagan, James
AU - Fleming, Jean
AU - Fong, Peter
AU - Forbes, John
AU - Fox, Stephen
AU - French, Juliet
AU - Friedlander, Michael
AU - Gaff, Clara
AU - Gardner, Mac
AU - Gattas, Mike
AU - George, Peter
AU - Giles, Graham
AU - Gill, Grantley
AU - Goldblatt, Jack
AU - Greening, Sian
AU - Grist, Scott
AU - Haan, Eric
AU - Hardie, Kate
AU - Harris, Marion
AU - Hart, Stewart
AU - Healey, Sue
AU - Heiniger, Louise
AU - Hopper, John
AU - Humphrey, Evelyn
AU - Hunt, Clare
AU - James, Paul
AU - Jenkins, Mark
AU - Jones, Alison
AU - Kefford, Rick
AU - Kidd, Alexa
AU - Kiely, Belinda
AU - Kirk, Judy
AU - Koehler, Jessica
AU - Kollias, James
AU - Kovalenko, Serguei
AU - Lakhani, Sunil
AU - Leaming, Amanda
AU - Leary, Jennifer
AU - Lindeman, Geoff
AU - Lipton, Lara
AU - Lobb, Liz
AU - Mann, Graham
AU - Marsh, Deborah
AU - McLachlan, Sue Anne
AU - Meiser, Bettina
AU - Meldrum, Cliff
AU - Milne, Roger
AU - Mitchell, Gillian
AU - Newman, Beth
AU - Niedermayr, Eveline
AU - Nightingale, Sophie
AU - O'Connell, Shona
AU - O'Loughlin, Imelda
AU - Osborne, Richard
AU - Pachter, Nick
AU - Patterson, Briony
AU - Peters, Lester
AU - Price, Melanie
AU - Purser, Lynne
AU - Reeve, Tony
AU - Reeve, Jeanne
AU - Richards, Robert
AU - Rickard, Edwina
AU - Robinson, Bridget
AU - Rudzki, Barney
AU - Saleh, Mona
AU - Salisbury, Elizabeth
AU - Sambrook, Joe
AU - Saunders, Christobel
AU - Saunus, Jodi
AU - Sayer, Robyn
AU - Scott, Clare
AU - Seshadri, Ram
AU - Sexton, Adrienne
AU - Sharma, Raghwa
AU - Shelling, Andrew
AU - Simpson, Peter
AU - Southey, Melissa
AU - Spurdle, Amanda
AU - Suthers, Graeme
AU - Sykes, Pamela
AU - Tassell, Margaret
AU - Taylor, Donna
AU - Thierry, Benjamin
AU - Thomas, Susan
AU - Thompson, Ella
AU - Thorne, Heather
AU - Townshend, Sharron
AU - Trainer, Alison
AU - Tran, Lan
AU - Tucker, Kathy
AU - Tyler, Janet
AU - Visvader, Jane
AU - Walker, Logan
AU - Walpole, Ian
AU - Ward, Robin
AU - Waring, Paul
AU - Warner, Bev
AU - Warren, Graham
AU - Williams, Rachael
AU - Wilson, Judy
AU - Winship, Ingrid
AU - Wu, Kathy
AU - Young, Mary Ann
AU - Bowtell, D.
AU - Gertig, D.
N1 - Funding Information:
Cancer Research UK (C1287/A10118, C1287/A12014, C490/A10124, C490/ A10119 and C490/A16561), the 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 (grants NKI 2007–3839, 2009–4363; DDHK 2004–3124, DDHK 2009–4318); Baden Württemberg Ministry of Science, Research and Arts, Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, the Nordic Cancer Union and the Sigrid Juselius Foundation, Special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, Australia National Breast Cancer Foundation, National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, the Cancer Foundation of Western Australia, NIH grants (CA128978, CA116167, CA176785), NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer Research Foundation, the David F and Margaret T Grohne Family Foundation, the Ting Tsung and Wei Fong Chao Foundation, Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA and CAPES Foundation. KAP is supported by a National Breast Cancer Foundation Practitioner Fellowship.
Publisher Copyright:
© 2015 Sobral-Leite et al.
PY - 2015/7/2
Y1 - 2015/7/2
N2 - 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.
AB - 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.
KW - Annexin A1
KW - BRCA1 and BRCA2 mutations
KW - Breast cancer
UR - http://www.scopus.com/inward/record.url?scp=84935085249&partnerID=8YFLogxK
U2 - 10.1186/s12916-015-0392-6
DO - 10.1186/s12916-015-0392-6
M3 - Article
C2 - 26137966
AN - SCOPUS:84935085249
SN - 1741-7015
VL - 13
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 156
ER -