Elevated insulin receptor content in human breast cancer.

Papa, Vincenzo; Pezzino, V.; Costantino, Angela; Belfiore, Antonino; Giuffrida, Dario; Frittitta, Lucia; Vannelli, G. B.; Brand, Randall E.; Goldfine, Ira D.; Vigneri, Riccardo

doi:10.1172/jci114868

Cited by 303 publications

(196 citation statements)

References 26 publications

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“…In a case-control investigation on subclinical diabetes, hyperinsulinaemia with insulin resistance was a significant risk factor for breast cancer, independent of weight or body fat distribution (Bruning et al, 1992). Hyperinsulinaemia, as in late-onset diabetes, may promote breast cancer, as insulin is an important growth factor for human breast cancer cells (Freiss et al, 1990) and elevated insulin receptor contents have been found in breast cancer specimens (Papa et al, 1990). Furthermore, insulin levels are inversely related to SHBG levels and, thus, positively related to available oestrogens and androgens.…”

Section: Discussionmentioning

confidence: 99%

Selected medical conditions and risk of breast cancer

Talamini

Franceschi²,

Favero³

et al. 1997

Br J Cancer

133

102

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Summary Several diseases are known or suspected to be associated with altered levels of hormones and growth factors that may influence breast cancer risk. To elucidate this possibility, we studied the relationship between 23 medical conditions or procedures and breast cancer risk by means of data from a multicentric case-control study conducted between 1991 and 1994 in six Italian areas. The study included 2569 histologically confirmed incident cases of breast cancer (median age 55 years, range 23-74 years) and 2588 control women (median age 56 years, range 20-74 years) admitted to the same hospitals as cases for a variety of acute conditions unrelated to known or suspected risk factors for breast cancer. After allowance for education, parity and body mass index, elevated odds ratios (ORs) emerged for history of diabetes mellitus in post-menopausal women (OR = 1.5, 95% Cl 1.1-2.0), hypertension in pregnancy (OR = 1.8, 95% Cl 1.0-3.4) and breast nodules (OR = 1.3, 95% Cl 1.0-1.7). Risk decreases were associated with ovarian ablation for ovarian cysts (OR = 0.5, 95% Cl 0.3-0.7) and with thyroid nodules (OR = 0.7, 95% Cl 0.5-0.9) but not with the combination of any type of benign thyroid disease. While most examined conditions seemed unrelated to breast cancer risk, the association with late-onset diabetes is of special interest as it suggests a role of hyperinsulinaemia and insulin resistance in breast cancer promotion. It also points to preventive lifestyle modifications.Keywords: breast cancer; diabetes; hypertension; benign breast disease; benign thyroid disease; ovarian cysts It has been hypothesized that breast cancer risk is determined by cell proliferation in response to sex hormones (Henderson et al, 1988) and possibly other hormones (e.g. thyroid hormones; Stewart et al, 1990) and growth factors [i.e. insulin-like growth factor (IGF-I); Kazer, 1995].In post-menopausal women, the involvement of oestrogens is suggested by the association of breast cancer with several hormone-related characteristics (e.g. age at menopause, parity, being overweight, etc.) (Franceschi et al, 1996a;Talamini et al, 1996). Several investigators found that post-menopausal women who subsequently developed breast cancer tended to show higher levels of oestrone, total and free oestradiol and a lower per cent of oestradiol bound to sex-hormone binding globulin (SHBG) than women who remained free of cancer (Toniolo et al, 1995;Lipworth et al, 1996). SHBG concentration determines oestrogen bioavailability and is influenced by several physiological and pathological conditions. Obesity, for instance, increases peripheral aromatization of androgens but also reduces SHBG concentration (Enriori and Reforzo-Membrives, 1984). Insulin and IGF-I are powerful negative regulators of SHBG synthesis in vitro and may stimulate breast cancer proliferation in several ways (Macaulay, 1992). In the presence of functioning ovaries (i.e. premenopausal women), the peripheral aromatization of androgens is relatively unimportant and the association between fe...

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Section: Discussionmentioning

confidence: 99%

Selected medical conditions and risk of breast cancer

Talamini

Franceschi²,

Favero³

et al. 1997

Br J Cancer

133

102

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“…Increased levels of insulin have been related to increased risk of breast cancer and mortality from it (47) and colon cancer (48). It has been shown that human breast cancer specimens have higher IR content than normal breast tissue and fibroadenoma specimens (49). Increasing evidence also suggests that, in breast cancers, there is higher expression of IR-A (14, 17).…”

Section: Is Ir Also a Target For Cancer Therapy?mentioning

confidence: 99%

Disrupting insulin-like growth factor signaling as a potential cancer therapy

Sachdev

Yee

2007

Molecular Cancer Therapeutics

325

182

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“…The insulin receptor (IR) is overexpressed both in breast cancer cells in culture, and in most human breast cancer specimens (Milazzo et al, 1992a;Papa et al, 1990). Insulin, via its own receptor, stimulates growth and metabolism in breast cancer cells (Milazzo et al, 1992a;Papa et al, 1990;Papa and Bel®ore, 1996;Dickson and Lippman, 1995), and when the IR is overexpressed in NIH3T3 or normal breast cells a ligand-dependent malignant phenotype is induced (Giorgino et al, 1991;Frittitta et al, 1995).…”

Section: Introductionmentioning

confidence: 99%