Intracystic epidermal growth factor level is predictive of breast-cancer risk in women with gross cystic disease of the breast

Boccardo, Francesco; Marenghi, C.; Ghione, G.; Pepe, Alessio; Parodi, Stefano; Rubagotti, Alessandra

doi:10.1002/1097-0215(20010720)95:4<260::aid-ijc1044>3.0.co;2-n

Cited by 10 publications

(3 citation statements)

References 13 publications

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“…The levels of EGF and TGF‐β2 were significantly different between both types, with higher levels of EGF (Fig. 1f) in type I cysts, and higher TGF‐β2 levels in type II cysts, as described previously 27,28 …”

Section: Resultssupporting

confidence: 81%

Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration

Enriori

Vázquez

Chiauzzi

et al. 2005

Clinical Endocrinology

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Section: Resultssupporting

confidence: 81%

Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration

Enriori

Vázquez

Chiauzzi

et al. 2005

Clinical Endocrinology

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“…Such an association may be even stronger when the IGF-I/IGFBP-3 ratio is utilized as a measure of IGF-I available for biological activity (19,20). On the other hand, some studies have found an association between type I breast cysts and risk of breast cancer (8,25). It should be noted that breast cysts are not considered to be pre-malignant lesions but simple markers of an increased risk affecting the whole organ (8).…”

Section: Discussionmentioning

confidence: 99%

Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts

Enriori

Fischer

Gori

et al. 2003

European Journal of Endocrinology

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Objective: Gross cystic disease (GCD) is the most common benign breast pathology. Although breast cysts are not considered pre-malignant lesions, an increased risk of breast cancer has been reported for patients with type I cysts ðNa þ =K þ , 3Þ: Furthermore, an augmented IGF-I/IGF-binding protein-3 (IGFBP-3) ratio has been described in breast cancer patients. The objective was to evaluate serum IGF-I and binding protein concentrations of type I and type II cyst patients as compared with healthy women. Methods: Twenty-four patients with type I cysts, 17 with type II cysts and 25 healthy women were evaluated. Serum IGF-I, IGFBP-3 and IGFBP-1 concentrations were measured by IRMA. Results: IGF-I concentrations were significantly higher in sera from patients with type I cysts than in patients with type II cysts. A highly significant decrease of IGFBP-3, the major IGFBP, was found in patients with type I cysts with respect to healthy women, whereas no significant difference was evident between the different cyst types. The IGF-I/IGFBP-3 ratio, an estimate of biologically active IGF-I, was very significantly higher in patients with type I cysts than in both type II patients and healthy women. IGFBP-1 levels were significantly lower in patients with type I than in controls and type II cysts. The IGF-I/IGFBP-1 ratio was significantly higher in patients with type I cysts than in type II bearers and healthy women. Estrogen levels correlated with IGF-I in patients and controls. Conclusions: The enhanced levels of IGF-I/IGFBP-3 found in patients with type I cysts could eventually be associated with the increased risk of breast cancer described for this group.

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“…All together, these findings support the idea of androgens being an important component of the endogenous milieu that favors apocrine cyst growth. Furthermore, a number of studies (Collette et al 1986, Boccardo et al 1988, Lai et al 1989, Pascall 1997, Boccardo et al 2001 found high levels of epidermal growth factor (EGF), a known stimulant of breast epithelial cell proliferation (Osborne et al 1980, Lippman et al 1986, Borellini & Oka 1989, in apocrine cysts' fluid and assumed that androgens were responsible for EGF secretion in the apocrine cells of the human breast, in analogy with what was observed in the apocrine glands of animals (Wales & Ebling 1971, Barthe et al 1974, Sheflin et al 1996. The EGF receptor (EGFR), also known as human epidermal growth factor1 (HER1), is part of the ErbB family of tyrosine kinase receptors, together with HER2, HER3 and HER4.…”

Section: :2mentioning

confidence: 97%

Androgen excess in breast cancer development: implications for prevention and treatment

Secreto

Girombelli

Krogh

2019

Endocrine-Related Cancer

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The aim of this review is to highlight the pivotal role of androgen excess in the development of breast cancer. Available evidence suggests that testosterone controls breast epithelial growth through a balanced interaction between its two active metabolites: cell proliferation is promoted by estradiol while it is inhibited by dihydrotestosterone. A chronic overproduction of testosterone (e.g. ovarian stromal hyperplasia) results in an increased estrogen production and cell proliferation that are no longer counterbalanced by dihydrotestosterone. This shift in the androgen/estrogen balance partakes in the genesis of ER-positive tumors. The mammary gland is a modified apocrine gland, a fact rarely considered in breast carcinogenesis. When stimulated by androgens, apocrine cells synthesize epidermal growth factor (EGF) that triggers the ErbB family receptors. These include the EGF receptor and the human epithelial growth factor 2, both well known for stimulating cellular proliferation. As a result, an excessive production of androgens is capable of directly stimulating growth in apocrine and apocrine-like tumors, a subset of ER-negative/AR-positive tumors. The key role of androgen excess in the genesis of different subtypes of breast cancer has significant clinical implications for both treatment and prevention. Our belief stems from a thorough analysis of the literature, where an abundance of evidence is present to justify a clinical trial that would investigate the effectiveness of treating the underlying excessive androgen production.

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Intracystic epidermal growth factor level is predictive of breast-cancer risk in women with gross cystic disease of the breast

Cited by 10 publications

References 13 publications

Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration

Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration

Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts

Androgen excess in breast cancer development: implications for prevention and treatment

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