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 P trend=0.057 and significant for
IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted P trend=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 (P interaction=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.