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Breast cancer hypoxia in relation to prognosis and benefit from radiotherapy after breast-conserving surgery in a large, randomised trial with long-term follow-up

Tutzauer, Julia LU orcid ; Sjöström, Martin LU ; Holmberg, Erik ; Karlsson, Per ; Killander, Fredrika LU ; Leeb-Lundberg, L M Fredrik LU ; Malmström, Per LU ; Niméus, Emma LU ; Fernö, Mårten LU and Jögi, Annika LU (2022) In British Journal of Cancer 126(8). p.1145-1156
Abstract

BACKGROUND: Breast-conserving surgery followed by radiotherapy is part of standard treatment for early-stage breast cancer. Hypoxia is common in cancer and may affect the benefit of radiotherapy. Cells adapt to hypoxic stress largely via the transcriptional activity of hypoxia-inducible factor (HIF)-1α. Here, we aim to determine whether tumour HIF-1α-positivity and hypoxic gene-expression signatures associated with the benefit of radiotherapy, and outcome.

METHODS: Tumour HIF-1α-status and expression of hypoxic gene signatures were retrospectively analysed in a clinical trial where 1178 women with primary T1-2N0M0 breast cancer were randomised to receive postoperative radiotherapy or not and followed 15 years for recurrence and 20... (More)

BACKGROUND: Breast-conserving surgery followed by radiotherapy is part of standard treatment for early-stage breast cancer. Hypoxia is common in cancer and may affect the benefit of radiotherapy. Cells adapt to hypoxic stress largely via the transcriptional activity of hypoxia-inducible factor (HIF)-1α. Here, we aim to determine whether tumour HIF-1α-positivity and hypoxic gene-expression signatures associated with the benefit of radiotherapy, and outcome.

METHODS: Tumour HIF-1α-status and expression of hypoxic gene signatures were retrospectively analysed in a clinical trial where 1178 women with primary T1-2N0M0 breast cancer were randomised to receive postoperative radiotherapy or not and followed 15 years for recurrence and 20 years for breast cancer death.

RESULTS: The benefit from radiotherapy was similar in patients with HIF-1α-positive and -negative primary tumours. Both ipsilateral and any breast cancer recurrence were more frequent in women with HIF-1α-positive primary tumours (hazard ratio, HR0-5 yrs1.9 [1.3-2.9], p = 0.003 and HR0-5 yrs = 2.0 [1.5-2.8], p < 0.0001). Tumour HIF-1α-positivity is also associated with increased breast cancer death (HR0-10 years 1.9 [1.2-2.9], p = 0.004). Ten of the 11 investigated hypoxic gene signatures correlated positively to HIF-1α-positivity, and 5 to increased rate/risk of recurrence.

CONCLUSIONS: The benefit of postoperative radiotherapy persisted in patients with hypoxic primary tumours. Patients with hypoxic primary breast tumours had an increased risk of recurrence and breast cancer death.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
126
issue
8
pages
1145 - 1156
publisher
Nature Publishing Group
external identifiers
  • pmid:35140341
  • scopus:85124403491
ISSN
1532-1827
DOI
10.1038/s41416-021-01630-4
language
English
LU publication?
yes
additional info
© 2021. The Author(s).
id
b78bc206-7b42-4745-be41-5f279dc4d1be
date added to LUP
2022-02-24 23:06:18
date last changed
2024-06-18 01:34:32
@article{b78bc206-7b42-4745-be41-5f279dc4d1be,
  abstract     = {{<p>BACKGROUND: Breast-conserving surgery followed by radiotherapy is part of standard treatment for early-stage breast cancer. Hypoxia is common in cancer and may affect the benefit of radiotherapy. Cells adapt to hypoxic stress largely via the transcriptional activity of hypoxia-inducible factor (HIF)-1α. Here, we aim to determine whether tumour HIF-1α-positivity and hypoxic gene-expression signatures associated with the benefit of radiotherapy, and outcome.</p><p>METHODS: Tumour HIF-1α-status and expression of hypoxic gene signatures were retrospectively analysed in a clinical trial where 1178 women with primary T1-2N0M0 breast cancer were randomised to receive postoperative radiotherapy or not and followed 15 years for recurrence and 20 years for breast cancer death.</p><p>RESULTS: The benefit from radiotherapy was similar in patients with HIF-1α-positive and -negative primary tumours. Both ipsilateral and any breast cancer recurrence were more frequent in women with HIF-1α-positive primary tumours (hazard ratio, HR0-5 yrs1.9 [1.3-2.9], p = 0.003 and HR0-5 yrs = 2.0 [1.5-2.8], p &lt; 0.0001). Tumour HIF-1α-positivity is also associated with increased breast cancer death (HR0-10 years 1.9 [1.2-2.9], p = 0.004). Ten of the 11 investigated hypoxic gene signatures correlated positively to HIF-1α-positivity, and 5 to increased rate/risk of recurrence.</p><p>CONCLUSIONS: The benefit of postoperative radiotherapy persisted in patients with hypoxic primary tumours. Patients with hypoxic primary breast tumours had an increased risk of recurrence and breast cancer death.</p>}},
  author       = {{Tutzauer, Julia and Sjöström, Martin and Holmberg, Erik and Karlsson, Per and Killander, Fredrika and Leeb-Lundberg, L M Fredrik and Malmström, Per and Niméus, Emma and Fernö, Mårten and Jögi, Annika}},
  issn         = {{1532-1827}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1145--1156}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Breast cancer hypoxia in relation to prognosis and benefit from radiotherapy after breast-conserving surgery in a large, randomised trial with long-term follow-up}},
  url          = {{http://dx.doi.org/10.1038/s41416-021-01630-4}},
  doi          = {{10.1038/s41416-021-01630-4}},
  volume       = {{126}},
  year         = {{2022}},
}