Circulating growth factor concentrations and breast cancer risk: a nested case-control study of IGF-1, IGFBP-3, and breast cancer in a family-based cohort

Abstract

Background Insulin-like growth factor 1 (IGF-1) and binding protein 3 (IGFBP-3) are associated with breast cancer in women at average risk of cancer. Less is known whether these biomarkers also predict risk in women with breast cancer family history. Methods We conducted a nested case-control study within the New York site of the Breast Cancer Family Registry (BCFR, n = 80 cases, 156 controls), a cohort enriched for breast cancer family history. Using conditional logistic regression, we estimated the association between IGF-1 and IGFBP-3 levels and breast cancer risk and examined whether this risk differed by predicted absolute breast cancer risk based on pedigree models. Results The overall association between IGF-1 or IGFBP-3 elevation (≥ median in controls) and breast cancer risk was elevated, but not statistically significant (IGF-1 OR = 1.37, 95% CI = 0.66–2.85; IGFBP-3 OR = 1.62, 95% CI = 0.81–3.24). Women with elevated predicted absolute 10-year risk ≥ 3.4% and elevated IGFBP-3 (≥ median) had more than a 3-fold increased risk compared to women with lower predicted absolute 10-year risk (< 3.4%) and low IGFBP-3 (OR = 3.47 95% CI = 1.04–11.6). Conclusions These data offer some support that the overall magnitude of the associations between IGF-1 and IGFBP3 seen in average risk cohorts may be similar in women enriched with a strong breast cancer family history.

A common IGF1R gene variant predicts later life breast cancer risk in women with preeclampsia

“…Moreover, both NHS2 and CTS studies also demonstrate that this protective mechanistic interaction appears strongest against HR + breast cancer, producing a 30-40% reduction in this most common subtype of breast cancer. Furthermore, these concordant NHS2 and CTS ndings are consistent with numerous preclinical and clinical studies examining the role of the IGF-1 axis in driving HR + breast cancers [27][28][29][30]. At a mechanistic level, it is now well-established that tumorigenic crosstalk occurs between the estrogen receptor (ER) axis and epithelial signal transduction downstream of activated IGF1R, and that this crosstalk plays a role in both HR + breast cancer development and progression [52][53][54][55].…”

“…IGF-1 plays an essential role in normal breast development; likewise, upregulation of the IGF-1 axis and increased IGF1R expression appears to be associated with the development of breast cancer [26][27][28][29]. A pooled analysis of 17 studies demonstrated that higher levels of circulating IGF-1 are associated with increased risk of breast cancer, with this being especially true for hormone receptor-positive (HR+) breast cancer [30]. Elevated serum levels or increased expression of IGF-1 has also been demonstrated in multiple non-breast cancers, and its role in cancer development is widely accepted [31][32][33][34][35].…”

Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

“…8 Similar associations also apply to women with a family history of breast cancer. 21 Total and calculated free oestradiol in pre-menopausal women Endogenous oestrogens may increase the risk of breast cancer by promoting cell proliferation and decreasing apoptosis. 1 Higher oestradiol concentrations have been consistently associated with an increased risk of post-menopausal breast cancer.…”

Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer

“…This is particularly verified for the incurrence of estrogen receptor positive (ER+) tumors, independent from menopausal status ( Key et al, 2010 ). Whether it constitutes an additional risk for women with a family history of disease is not yet clarified ( Monson et al, 2020 ). However, an Italian study associated an increased risk of BC in patients with BRCA mutation (hereditary BC) with high serum IGF-1 levels ( Pasanisi et al, 2011 ).…”