From Archives of Internal Medicine:

Combined Estrogen and Testosterone Use and Risk of Breast Cancer in
Postmenopausal Women
Rulla M. Tamimi, ScD; Susan E. Hankinson, ScD; Wendy Y. Chen, MD; Bernard
Rosner, PhD; Graham A. Colditz, MD, DrPH

Arch Intern Med. 2006;166:1483-1489.

Background  The role of androgens in breast cancer etiology has been
unclear. Epidemiologic studies suggest that endogenous testosterone levels
are positively associated with breast cancer risk in postmenopausal women.
Given the increasing trend in the use of hormone therapies containing
androgens, we evaluated the relation between the use of estrogen and
testosterone therapies and breast cancer.

Methods  We conducted a prospective cohort study in the Nurses' Health
Study from 1978 to 2002 to assess the risk of breast cancer associated with
different types of postmenopausal hormone (PMH) formulations containing
testosterone. During 24 years of follow-up (1 359 323 person-years), 4610
incident cases of invasive breast cancer were identified among
postmenopausal women. Information on menopausal status, PMH use, and breast
cancer diagnosis was updated every 2 years through questionnaires.

Results  Among women with a natural menopause, the risk of breast cancer
was nearly 2.5-fold greater among current users of estrogen plus
testosterone therapies (multivariate relative risk, 2.48; 95% confidence
interval, 1.53-4.04) than among never users of PMHs. This analysis showed
that risk of breast cancer associated with current use of estrogen and
testosterone therapy was significantly greater compared with estrogen-only
therapy (P for heterogeneity, .007) and marginally greater than estrogen
and progesterone therapy (P for heterogeneity, .11). Women receiving PMHs
with testosterone had a 17.2% (95% confidence interval, 6.7%-28.7%)
increased risk of breast cancer per year of use.

Conclusion  Consistent with the elevation in risk for endogenous
testosterone levels, women using estrogen and testosterone therapies have a
significantly increased risk of invasive breast cancer.