The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: a nested case-control study

Abstract

IntroductionSex and growth hormones are positively associated with postmenopausal breast cancer risk. However, few studies have evaluated the influence of multiple hormones simultaneously.MethodsWe considered the roles of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate and prolactin and, secondarily, insulin-like growth factor 1 (IGF-1) and c-peptide in postmenopausal breast cancer risk among 265 cases and 541 controls in the prospective Nurses' Health Study. We created several hormone scores, including ranking women by the number of hormones above the age- and batch-adjusted geometric mean and weighting hormone values by their individual associations with breast cancer risk.ResultsWomen in the top versus bottom quintile of individual estrogen or androgen levels had approximately a doubling of postmenopausal breast cancer risk. Having seven or eight compared to zero hormones above the geometric mean level was associated with total (RR = 2.7, 95% CI = 1.3 to 5.7, P trend < 0.001) and estrogen receptor (ER)-positive (RR = 3.4, 95% CI = 1.3 to 9.4, P trend < 0.001) breast cancer risk. When comparing the top versus bottom quintiles of the score weighted by individual hormone associations, the RR for total breast cancer was 3.0 (95% CI = 1.8 to 5.0, P trend < 0.001) and the RR for ER-positive disease was 3.9 (95% CI = 2.0 to 7.5, P trend < 0.001). The risk further increased when IGF-1 and c-peptide were included in the scores. The results did not change with adjustment for body mass index.ConclusionsOverall, the results of our study suggest that multiple hormones with high circulating levels substantially increase the risk of breast cancer, particularly ER-positive disease. Additional research should consider the potential impact of developing risk prediction scores that incorporate multiple hormones.

Height, Sitting Height, and Leg Length in Relation with Breast Cancer Risk in the E3N Cohort

“…Our results can also be explained by the increased IGF-I levels, acting as a potential cancer promoter, observed in prepubertal children with low birth weight and postnatal catch-up growth (20). IGF-1 levels can act as a potential cancer promoter by inhibiting apoptosis and increasing the differentiation of cells (21), particularly of ER þ subtype (22). But the association between IGF-1 levels in childhood and IGF-1 levels at adulthood is discussed (23).…”

Obesity, type 2 diabetes, and cancer: the insulin and IGF connection

“…The estrogen receptor and the IGF1R can work together to activate MAPK, thus stimulating tumor cell proliferation (Lee et al 1999). A recent study by Tworoger et al (2011) demonstrated that women with increased estrogen levels had an elevated risk of postmenopausal breast cancer, which further increased in women with increased IGF1 and c-peptide. This suggests that it is the interplay of the increased estrogen and insulin and IGF1 that is involved in the development of postmenopausal breast cancer.…”

Stromal–epithelial interactions modulate cross-talk between prolactin receptor and HER2/Neu in breast cancer

“…PRL mediates its effects via the PRL receptor (PRLR) [7] and stimulates signaling via the Jak2-STAT5 [8][9][10], Ras-Raf-MAPK [11][12][13], and PI3K-Akt pathways. Studies have shown that PRLR is expressed in a majority of human breast cancers and is elevated in comparison with normal breast tissue [14][15][16] and that PRL levels are associated with increased breast cancer risk [17][18][19].…”