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Pre- and Postoperative Antioxidant Use, Aryl Hydrocarbon Receptor (AhR) Activation and Clinical Outcome in Different Treatment Groups of Breast Cancer Patients

Nilsson, Linn LU ; Khazaei, Somayeh LU ; Tryggvadottir, Helga LU ; Björner, Sofie LU ; Bressan, Alessandra ; Jirström, Karin LU orcid ; Adrian, Gabriel LU orcid ; Falck, Anna-Karin LU ; Borgquist, Signe LU and Isaksson, Karolin LU , et al. (2024) In Clinical Breast Cancer 24(3). p.152-166
Abstract

BACKGROUND: Cancer patients often use antioxidants that may interact with adjuvant treatments. The purpose was to investigate pre- and postoperative antioxidant use in relation to clinicopathological characteristics and prognosis in different breast cancer treatment groups.

METHODS AND PATIENTS: Pre- and postoperative antioxidant (vitamin A, C, E, carotenoids, or Q10) or multivitamin use was self-reported by patients from Lund (n = 1855) and Helsingborg (n=478), Sweden. Patients were followed for up to 15 years. Clinical data were obtained from patient charts. The aryl hydrocarbon receptor (AhR) was evaluated in tumor tissue arrays from 915 patients from Lund and with Western blot in MCF-7 and MDA-MB-231 cells.

RESULTS:... (More)

BACKGROUND: Cancer patients often use antioxidants that may interact with adjuvant treatments. The purpose was to investigate pre- and postoperative antioxidant use in relation to clinicopathological characteristics and prognosis in different breast cancer treatment groups.

METHODS AND PATIENTS: Pre- and postoperative antioxidant (vitamin A, C, E, carotenoids, or Q10) or multivitamin use was self-reported by patients from Lund (n = 1855) and Helsingborg (n=478), Sweden. Patients were followed for up to 15 years. Clinical data were obtained from patient charts. The aryl hydrocarbon receptor (AhR) was evaluated in tumor tissue arrays from 915 patients from Lund and with Western blot in MCF-7 and MDA-MB-231 cells.

RESULTS: About 10% of patients used antioxidants. Nuclear AhR (AhRnuc) positivity was twice as common in preoperative antioxidant users compared to non-users. In mechanistic studies vitamin C increased AhR levels and its downstream target CYP1B1, indicating AhR activation. There were significant interactions between tumor AhRnuc status and preoperative antioxidant use in relation to clinical outcome. In all patients, antioxidant use (other than multivitamins) at both visits was associated with poorer prognosis, while use only at the follow-up visit was associated with better prognosis, compared with no use at either visit.

CONCLUSION: The clinical impact of antioxidants depended on antioxidant type, timing of use, and tumor AhR activation. Antioxidants may influence clinical outcome by activation of the master regulator AhR in addition to interference with free radicals. Further studies are needed to identify breast patients that might improve or worsen their prognosis when using antioxidants postoperatively.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Breast Cancer
volume
24
issue
3
pages
152 - 166
publisher
Elsevier
external identifiers
  • pmid:38307727
  • scopus:85183962277
ISSN
1526-8209
DOI
10.1016/j.clbc.2023.12.002
language
English
LU publication?
yes
id
7af1d479-4814-4068-b257-3d7bcbf2983a
date added to LUP
2024-02-07 12:54:53
date last changed
2024-04-12 11:45:08
@article{7af1d479-4814-4068-b257-3d7bcbf2983a,
  abstract     = {{<p>BACKGROUND: Cancer patients often use antioxidants that may interact with adjuvant treatments. The purpose was to investigate pre- and postoperative antioxidant use in relation to clinicopathological characteristics and prognosis in different breast cancer treatment groups.</p><p>METHODS AND PATIENTS: Pre- and postoperative antioxidant (vitamin A, C, E, carotenoids, or Q10) or multivitamin use was self-reported by patients from Lund (n = 1855) and Helsingborg (n=478), Sweden. Patients were followed for up to 15 years. Clinical data were obtained from patient charts. The aryl hydrocarbon receptor (AhR) was evaluated in tumor tissue arrays from 915 patients from Lund and with Western blot in MCF-7 and MDA-MB-231 cells.</p><p>RESULTS: About 10% of patients used antioxidants. Nuclear AhR (AhRnuc) positivity was twice as common in preoperative antioxidant users compared to non-users. In mechanistic studies vitamin C increased AhR levels and its downstream target CYP1B1, indicating AhR activation. There were significant interactions between tumor AhRnuc status and preoperative antioxidant use in relation to clinical outcome. In all patients, antioxidant use (other than multivitamins) at both visits was associated with poorer prognosis, while use only at the follow-up visit was associated with better prognosis, compared with no use at either visit.</p><p>CONCLUSION: The clinical impact of antioxidants depended on antioxidant type, timing of use, and tumor AhR activation. Antioxidants may influence clinical outcome by activation of the master regulator AhR in addition to interference with free radicals. Further studies are needed to identify breast patients that might improve or worsen their prognosis when using antioxidants postoperatively.</p>}},
  author       = {{Nilsson, Linn and Khazaei, Somayeh and Tryggvadottir, Helga and Björner, Sofie and Bressan, Alessandra and Jirström, Karin and Adrian, Gabriel and Falck, Anna-Karin and Borgquist, Signe and Isaksson, Karolin and Jernström, Helena}},
  issn         = {{1526-8209}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{152--166}},
  publisher    = {{Elsevier}},
  series       = {{Clinical Breast Cancer}},
  title        = {{Pre- and Postoperative Antioxidant Use, Aryl Hydrocarbon Receptor (AhR) Activation and Clinical Outcome in Different Treatment Groups of Breast Cancer Patients}},
  url          = {{http://dx.doi.org/10.1016/j.clbc.2023.12.002}},
  doi          = {{10.1016/j.clbc.2023.12.002}},
  volume       = {{24}},
  year         = {{2024}},
}