Table 1

Epidemiological studies on the association between androgens and breast cancer risk

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

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.

Dimitrakakis and Bondy Breast Cancer Research 2009 11:212   doi:10.1186/bcr2413