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
(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
- Tutzauer, Julia LU ; 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
- organization
- publishing date
- 2022
- 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
- 2024-09-10 06:11:15
@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 < 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}}, }