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

kConFab/AOCS Investigators; 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 Lissowska; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Kelly-Anne Phillips; 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

doi:10.1186/s12916-015-0392-6

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

kConFab/AOCS Investigators, 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 ShermanJolanta Lissowska, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Kelly-Anne Phillips, 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

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	156
Journal	BMC Medicine
Volume	13
DOIs	https://doi.org/10.1186/s12916-015-0392-6
Publication status	Published - 2 Jul 2015

Keywords / Materials (for Non-textual outputs)

Adult
Annexin A1
Biomarkers, Tumor
Breast Neoplasms
Female
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Middle Aged
Mutation
Prognosis

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10.1186/s12916-015-0392-6

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kConFab/AOCS Investigators, Sobral-Leite, M., Wesseling, J., Smit, V. T. H. B. M., Nevanlinna, H., van Miltenburg, M. H., Sanders, J., Hofland, I., Blows, F. M., Coulson, P., Patrycja, G., Schellens, J. H. M., Fagerholm, R., Heikkilä, P., Aittomäki, K., Blomqvist, C., Provenzano, E., Ali, H. R., Figueroa, J., ... Schmidt, M. K. (2015). Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis. BMC Medicine, 13, 156. https://doi.org/10.1186/s12916-015-0392-6

@article{9676b1a1793b484ababd9193e7632c2e,

title = "Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis",

abstract = "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.",

keywords = "Adult, Annexin A1, Biomarkers, Tumor, Breast Neoplasms, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Middle Aged, Mutation, Prognosis",

author = "{kConFab/AOCS Investigators} and Marcelo Sobral-Leite and Jelle Wesseling and Smit, {Vincent T H B M} and Heli Nevanlinna and {van Miltenburg}, {Martine H} and Joyce Sanders and Ingrid Hofland and Blows, {Fiona M} and Penny Coulson and Gazinska Patrycja and Schellens, {Jan H M} and Rainer Fagerholm and P{\"a}ivi Heikkil{\"a} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Elena Provenzano and Ali, {Hamid Raza} and Jonine Figueroa and Mark Sherman and Jolanta Lissowska and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M} and Kelly-Anne Phillips and Couch, {Fergus J} and Olson, {Janet E} and Celine Vachon and Daniel Visscher and Hermann Brenner and Katja Butterbach and Volker Arndt and Bernd Holleczek and Hooning, {Maartje J} and Antoinette Hollestelle and Martens, {John W M} and {van Deurzen}, {Carolien H M} and {van de Water}, Bob and Annegien Broeks and Jenny Chang-Claude and Georgia Chenevix-Trench and Easton, {Douglas F} and Pharoah, {Paul D P} and Montserrat Garc{\'i}a-Closas and {de Graauw}, Marjo and Schmidt, {Marjanka K}",

year = "2015",

month = jul,

day = "2",

doi = "10.1186/s12916-015-0392-6",

language = "English",

volume = "13",

pages = "156",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central",

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kConFab/AOCS Investigators, Sobral-Leite, M, Wesseling, J, Smit, VTHBM, Nevanlinna, H, van Miltenburg, MH, Sanders, J, Hofland, I, Blows, FM, Coulson, P, Patrycja, G, Schellens, JHM, Fagerholm, R, Heikkilä, P, Aittomäki, K, Blomqvist, C, Provenzano, E, Ali, HR, Figueroa, J, Sherman, M, Lissowska, J, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Phillips, K-A, Couch, FJ, Olson, JE, Vachon, C, Visscher, D, Brenner, H, Butterbach, K, Arndt, V, Holleczek, B, Hooning, MJ, Hollestelle, A, Martens, JWM, van Deurzen, CHM, van de Water, B, Broeks, A, Chang-Claude, J, Chenevix-Trench, G, Easton, DF, Pharoah, PDP, García-Closas, M, de Graauw, M & Schmidt, MK 2015, 'Annexin A1 expression in a pooled breast cancer series: association with tumor subtypes and prognosis', BMC Medicine, vol. 13, pp. 156. https://doi.org/10.1186/s12916-015-0392-6

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

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 - Adult

KW - Annexin A1

KW - Biomarkers, Tumor

KW - Breast Neoplasms

KW - Female

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Genetic Predisposition to Disease

KW - Humans

KW - Immunohistochemistry

KW - Middle Aged

KW - Mutation

KW - Prognosis

U2 - 10.1186/s12916-015-0392-6

DO - 10.1186/s12916-015-0392-6

M3 - Article

C2 - 26137966

SN - 1741-7015

VL - 13

SP - 156

JO - BMC Medicine

JF - BMC Medicine

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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