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Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence : A Nested Case-Control Study

Rosendahl, Ann H. LU ; Björner, Sofie LU ; Ygland Rödström, Maria ; Jirström, Karin LU ; Borgquist, Signe LU ; Ingvar, Christian LU ; Pollak, Michael N. and Jernström, Helena LU (2021) In Frontiers in Oncology 11.
Abstract

Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the... (More)

Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002–2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IRm) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted Ptrend=0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted Ptrend=0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IRm positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IRm positive tumors but not in those with IGF-IRm negative tumors (Pinteraction=0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER+ tumors. Postoperative changes >10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, IGF-I, IGF-IR, IGFBP-3, IGFBP-7, recurrence
in
Frontiers in Oncology
volume
11
article number
626058
publisher
Frontiers Media S. A.
external identifiers
  • pmid:33767994
  • scopus:85103012042
ISSN
2234-943X
DOI
10.3389/fonc.2021.626058
language
English
LU publication?
yes
id
f3c3c193-ec71-4f23-ae0c-30343f28bf94
date added to LUP
2021-04-08 08:35:29
date last changed
2021-06-16 06:00:20
@article{f3c3c193-ec71-4f23-ae0c-30343f28bf94,
  abstract     = {<p>Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002–2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IR<sup>m</sup>) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted P<sub>trend</sub>=0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted P<sub>trend</sub>=0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IR<sup>m</sup> positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IR<sup>m</sup> positive tumors but not in those with IGF-IR<sup>m</sup> negative tumors (P<sub>interaction</sub>=0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER<sup>+</sup> tumors. Postoperative changes &gt;10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.</p>},
  author       = {Rosendahl, Ann H. and Björner, Sofie and Ygland Rödström, Maria and Jirström, Karin and Borgquist, Signe and Ingvar, Christian and Pollak, Michael N. and Jernström, Helena},
  issn         = {2234-943X},
  language     = {eng},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Oncology},
  title        = {Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence : A Nested Case-Control Study},
  url          = {http://dx.doi.org/10.3389/fonc.2021.626058},
  doi          = {10.3389/fonc.2021.626058},
  volume       = {11},
  year         = {2021},
}