Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study

Abstract Background Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that facilitates the adaptation of cancer cells to hypoxic conditions and may be prognostic of breast cancer recurrence. We evaluated the association of HIF-1α expression with breast cancer recurrence, and its associa...

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Autores principales:	Lindsay J. Collin, Maret L. Maliniak, Deirdre P. Cronin-Fenton, Thomas P. Ahern, Kristina B. Christensen, Sinna P. Ulrichsen, Per Damkier, Stephen Hamilton-Dutoit, Rami Yacoub, Peer M. Christiansen, Henrik Toft Sørensen, Timothy L. Lash
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Breast cancer recurrence Hypoxia-inducible factor 1 Tamoxifen resistance Prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e0c79d047b0e44008c364411791a4412
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spelling	oai:doaj.org-article:e0c79d047b0e44008c364411791a44122021-11-07T12:18:46ZHypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study10.1186/s13058-021-01480-11465-542Xhttps://doaj.org/article/e0c79d047b0e44008c364411791a44122021-11-01T00:00:00Zhttps://doi.org/10.1186/s13058-021-01480-1https://doaj.org/toc/1465-542XAbstract Background Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that facilitates the adaptation of cancer cells to hypoxic conditions and may be prognostic of breast cancer recurrence. We evaluated the association of HIF-1α expression with breast cancer recurrence, and its association with timing of breast cancer recurrence. Methods In this population-based case-control study, we included women diagnosed with stage I–III breast cancer between 1985 and 2001, aged 35–69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with estrogen receptor (ER)-positive disease who were treated with tamoxifen for at least 1 year (ER+ TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER-negative disease, not treated with tamoxifen, who survived at least 1 year (ER−/TAM−). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, cancer stage, and county of residence. Expression of HIF-1α was measured by immunohistochemistry on tissue microarrays. We fitted logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating HIF-1α expression with recurrence, and with timing of recurrence. Results HIF-1α expression was observed in 23% of cases and 20% of controls in the ER+/TAM+ stratum, and in 47% of cases and 48% of controls in the ER−/TAM− stratum. We observed a near-null association between HIF-1α expression in both ER/TAM groups (ER+/TAM+ OR = 1.21, 95%CI 0.88, 1.67 and ER−/TAM− OR = 0.97, 95%CI 0.68, 1.39). HIF-1α expression was not associated with time to recurrence among women in the ER+/TAM+ stratum, but was associated with early recurrence among women in the ER−/TAM− stratum. Conclusion In this study, HIF-1α expression was not associated with breast cancer recurrence overall but may be associated with early recurrence among women diagnosed with ER− breast cancer.Lindsay J. CollinMaret L. MaliniakDeirdre P. Cronin-FentonThomas P. AhernKristina B. ChristensenSinna P. UlrichsenPer DamkierStephen Hamilton-DutoitRami YacoubPeer M. ChristiansenHenrik Toft SørensenTimothy L. LashBMCarticleBreast cancer recurrenceHypoxia-inducible factor 1Tamoxifen resistancePrognostic markerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer Research, Vol 23, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Breast cancer recurrence Hypoxia-inducible factor 1 Tamoxifen resistance Prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Breast cancer recurrence Hypoxia-inducible factor 1 Tamoxifen resistance Prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lindsay J. Collin Maret L. Maliniak Deirdre P. Cronin-Fenton Thomas P. Ahern Kristina B. Christensen Sinna P. Ulrichsen Per Damkier Stephen Hamilton-Dutoit Rami Yacoub Peer M. Christiansen Henrik Toft Sørensen Timothy L. Lash Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
description	Abstract Background Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that facilitates the adaptation of cancer cells to hypoxic conditions and may be prognostic of breast cancer recurrence. We evaluated the association of HIF-1α expression with breast cancer recurrence, and its association with timing of breast cancer recurrence. Methods In this population-based case-control study, we included women diagnosed with stage I–III breast cancer between 1985 and 2001, aged 35–69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with estrogen receptor (ER)-positive disease who were treated with tamoxifen for at least 1 year (ER+ TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER-negative disease, not treated with tamoxifen, who survived at least 1 year (ER−/TAM−). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, cancer stage, and county of residence. Expression of HIF-1α was measured by immunohistochemistry on tissue microarrays. We fitted logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating HIF-1α expression with recurrence, and with timing of recurrence. Results HIF-1α expression was observed in 23% of cases and 20% of controls in the ER+/TAM+ stratum, and in 47% of cases and 48% of controls in the ER−/TAM− stratum. We observed a near-null association between HIF-1α expression in both ER/TAM groups (ER+/TAM+ OR = 1.21, 95%CI 0.88, 1.67 and ER−/TAM− OR = 0.97, 95%CI 0.68, 1.39). HIF-1α expression was not associated with time to recurrence among women in the ER+/TAM+ stratum, but was associated with early recurrence among women in the ER−/TAM− stratum. Conclusion In this study, HIF-1α expression was not associated with breast cancer recurrence overall but may be associated with early recurrence among women diagnosed with ER− breast cancer.
format	article
author	Lindsay J. Collin Maret L. Maliniak Deirdre P. Cronin-Fenton Thomas P. Ahern Kristina B. Christensen Sinna P. Ulrichsen Per Damkier Stephen Hamilton-Dutoit Rami Yacoub Peer M. Christiansen Henrik Toft Sørensen Timothy L. Lash
author_facet	Lindsay J. Collin Maret L. Maliniak Deirdre P. Cronin-Fenton Thomas P. Ahern Kristina B. Christensen Sinna P. Ulrichsen Per Damkier Stephen Hamilton-Dutoit Rami Yacoub Peer M. Christiansen Henrik Toft Sørensen Timothy L. Lash
author_sort	Lindsay J. Collin
title	Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
title_short	Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
title_full	Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
title_fullStr	Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
title_full_unstemmed	Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study
title_sort	hypoxia-inducible factor-1α expression and breast cancer recurrence in a danish population-based case control study
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e0c79d047b0e44008c364411791a4412
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Hypoxia-inducible factor-1α expression and breast cancer recurrence in a Danish population-based case control study

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