SEX HORMONE-BINDING
GLOBULIN AND
BREAST CANCER RISK
Lila E. Nachtigall, MD
Epidemiologic evidence supports
the hypothesis that a woman’s
cumulative exposure to premenopausal
ovarian steroids, estrogen
and progesterone, contributes to
the lifetime risk of developing
breast cancer. A direct relationship
between total endogenous
levels of plasma estrogens and
the incidence of breast carcinoma
has not been demonstrated,
however, and no substantial
breast cancer risk has
been consistently associated with
postmenopausal estrogen replacement
therapy. This paper
summarizes the literature regarding
the potential role of sex
hormone-binding globulin
(SHBG) in modifying breast cancer
risk. It has been proposed
that circulating levels of bioavailable
estrogens (ie, not
bound to SHBG) might more directly
reflect the risk for development
of disease. Several studies
have detected an association
between a decreased percentage
of estradiol bound to SHBG, a
small increase in free estradiol,
and a higher incidence of breast
cancer in postmenopausal
women. The physiologic significance
of this increase in free
estradiol, however, especially
considered in the context of the
relatively lower postmenopausal
levels of total estradiol, is not
clear. In addition to its carrier
function for circulating estradiol,
SHBG specifically binds to cells
of steroid-responsive tissues, including
breast tissue, and decreases
the proliferation of some
breast cancer cells through activation
of cyclic adenosine monophosphate.
This suggests that a
decrease in the binding capacity
of SHBG could potentially diminish
SHBG binding to breast cell
membranes and increase the rate
of cellular proliferation. Oral estrogens
increase plasma SHBG
levels in postmenopausal women
and this increase might mitigate
the effect of estrogen replacement
therapy on breast cancer
epidemiology. (Prim Care Update
Ob/Gyns 1999;6:39 – 45.
© 1999 Elsevier Science