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 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.
Highlights
Breast cancer is the most common type of cancer among women and with novel diagnostic and therapeutic modalities is often a treatable disease
There is prior evidence that systemic Insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) are associated with risk of breast cancer [4, 11], but insulin-like growth factor-binding protein 7 (IGFBP-7) has not been studied in this context
The present study demonstrates that preoperative levels of insulin-like growth factor (IGF)-I or IGF binding proteins (IGFBPs)-3 are positively associated with risk of breast cancer recurrence, which is in contrast to a recent study of Danish postmenopausal patients [28]
Summary
Breast cancer is the most common type of cancer among women and with novel diagnostic and therapeutic modalities is often a treatable disease. For women diagnosed with metastatic or recurrent breast cancer, the prognosis is poor. Means to better predict clinical outcome and to identify women at risk of breast cancer recurrence may be helpful to optimize individual treatment decisions and improve prognosis. Insulin-like growth factor I (IGF-I) has a well-established role as a mitogenic peptide growth factor and has been suggested in multiple studies to be associated with predisposition of several types of cancer [1, 2]. An early groundbreaking clinical report demonstrated that pre-menopausal women with higher circulating IGF-I levels (top tertile) had an increased risk of breast cancer, compared with patients with lower levels (bottom tertile) [3]. Subsequent reports have supported a positive association between systemic IGF-I levels and breast cancer risk among pre-menopausal, and among post-menopausal women [4,5,6]. Some early promising reports, large phase III clinical trials have not shown clear clinical benefit, which may relate to the complexity of the IGF system, suboptimum dosing of drug candidates, as well as inadequate patient selection of probable responders, as reviewed in [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
