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Table 1 Epidemiological studies on the association between androgens and breast cancer risk

From: Androgens and the breast

Study Conclusion
Elevated levels of androgens (and estrogens) are associated with increased risk of breast cancer
Tamimi et al. 2006 [47] Prospective cohort study in Nurses' Health Study with over a million person-years studied: women receiving postmenopausal hormones with testosterone had a 17.2% increased risk of breast cancer per year of use
Micheli et al. 2007 [54] Breast cancer patients (n = 194) with high testosterone had significantly lower event-free survival than those with low testosterone (P = 0.004) and a significantly higher risk of breast cancer events with an adjusted hazard ratio of 1.77 (95% CI, 1.06 to 2.96)
The Endogenous Hormones and Breast Cancer Collaborative Group 2002 [34] Meta-analysis: breast cancer risk increases statistically significantly with increasing concentrations of almost all sex hormones
Tworoger et al. 2006 [31] Prospective nested case-control study within the Nurses' Health Study II: adrenal androgens are positively associated with breast cancer among predominately premenopausal women (for example, for DHEA: RR, 1.6; 95% CI, 0.9 to 2.8; P = 0.09)
Eliassen et al. 2006 [29] Nurses' Health Study II, nested: higher levels of testosterone and androstenedione in 18,521 premenopausal women are associated with insignificant overall increase in breast cancer risk, but increased risk of invasive and ER+/PR+ cancers (for example, RR = 2.9; CI = 1.4 to 6.0)
Androgen levels acting with protective patterns
Hofling et al. 2007 [51] Randomized, double-blind, placebo-controlled study: testosterone use inhibited exogenous estrogen-induced breast tissue proliferation in 99 postmenopausal women (P < 0.001)
Dimitrakakis et al. 2004 [48] Retrospective, observational study that followed 508 postmenopausal women receiving testosterone in addition to usual hormone therapy: incidence of breast cancer in testosterone users was substantially less than in women receiving estrogen/progestin in the WHI study and in the Million-woman study
Suzuki et al. 2001 [55] Intratumoral dihydrotestosterone inhibits cancer cell proliferation in hormone-dependent human breast carcinoma
Haiman et al. 2002 [18] A case-control study nested within the Nurses' Health Study cohort (cases, n = 727; controls, n = 969): longer CAG repeat alleles of AR increases breast cancer risk (odds ratio, 1.70; 95% CI, 1.20 to 2.40; P = 0.04)
MacLean et al. 2004 [19] Forty-one male breast cancers were studied: incidence of longer CAG repeats in AR was significantly higher in the breast cancer group than in the normal population (P < 0.05)
Ogawa et al. 2008 [25] In 227 primary breast cancers, AR expression was significantly higher in breast tumors with favorable characteristics
Dimitrakakis et al. 2009 [30] Testosterone and DHEA-S salivary levels were statistically significantly lower in breast cancer patients compared to controls (n = 541)
No association between serum concentrations of androgens and breast cancer risk
Ness et al. 2009 [46] A group of postmenopausal participants in the WHI study used testosterone combined with estrogens: testosterone addition had no statistically significant effect on breast cancer occurrence
Cox et al. 2006 [17] Among postmenopausal women, common variants of the AR gene are not associated with risk of breast cancer
Page et al. 2004 [28] Prospective observational study: no relationship between serum DHEA or DHEA-S and subsequent breast cancer in middle-aged women
Olson et al. 2007 [32] No association with breast cancer risk was detected for individual variants of CYP19 mutation in 750 cases
Adly et al. 2006 [37] Serum levels of steroids in 331 women: androgen levels were not independently associated with increased risk of breast cancer
Beattie et al. 2006 [38] Case-cohort design including 135 postmenopausal women with and 275 without breast cancer enrolled in the NSABBP P-1 trial: risk of breast cancer was not associated with sex hormone levels
  1. AR, androgen receptor; CI, confidence interval; DHEA, dehydroepiandrosterone; DHEA-S, DHEA sulfate; ER, estrogen receptor; NSABBP, National Surgical Adjuvant Breast and Bowel Project; PR, progesterone receptor; RR, relative risk; WHI, Women's Health Initiative.