Increased Estrogen Production Could Increase Risk of Breast Cancer
Reported August 17, 2011
(Ivanhoe Newswire) – Some women who naturally produce excess estrogen in
their breasts are at an increased risk for developing breast cancer,
according to this study conducted by researchers at Georgetown Lombardi
Comprehensive Cancer Center.
The investigators say their mice study shows that overproduction of
aromatase, which converts testosterone into estrogen, in breast tissue is
even more important in pushing breast cancer development than excess
production of the estrogen receptor that the hormone uses to activate
mammary cells. In addition, the researchers found that aromatase
over-expressing mice also expressed more estrogen receptors on the breast
While current breast cancer therapies target both of those processes —
inhibition of aromatase and inactivation of the estrogen receptor — the
researchers say this study suggests that aromatase inhibitors may prove to
be a more potent choice for cancer prevention in postmenopausal women.
Tamoxifen and other drugs that block the estrogen receptor have long been
used to prevent breast cancer and deter recurrence, while aromatase
inhibitors are only now being studied as a protectant.
"We know that estrogen is the fuel that most breast tumors use to grow, and
this study shows us that making more estrogen in the breast, right next to
cells that can use the hormone as fuel, appears to be a key trigger of early
breast cancer," the study's senior investigator, Priscilla Furth, M.D.,
professor of oncology and medicine at Georgetown Lombardi, was quoted as
"This study appears to help inform a longstanding controversy about whether
it is systemic estrogen or estrogen produced in the breast that is the
primary risk factor for breast cancer," Edgar Díaz-Cruz, Ph.D., a
postdoctoral researcher working in the Furth laboratory and first author of
the study, was quoted as saying. "With our animal models, we've demonstrated
that local production of estrogen in mammary tissue is potent enough to spur
development of breast cancer, and does not require estrogen from the ovaries
or produced from fat tissue, as had been hypothesized."
The researchers developed the first "conditional" mouse model of aromatase
production in mammary tissue. That means they inserted a gene into mice that
expresses human aromatase in the animal's mammary tissue — a gene the
researchers can turn on or off. They compared this new mouse model to one
they had developed several years ago —a conditional mouse model in which a
gene that produces estrogen receptors (ER) could also be turned on and off.
While they study found that both mouse models experienced the earliest
stages of tumor formation, known as preneoplasia, the aromatase
over-expressing mice model exhibited both increased preneoplasia and
outright development of cancer. These mice also expressed proteins that are
tightly linked to cancer, Furth says.
The researchers also found, to their surprise, that aromatase
over-expressing mice expressed more estrogen receptors than did the
ER-conditional mice. "Increased aromatase produced both more estrogen and
the receptors that the hormone needs to enter breast cells," said Díaz-Cruz.
"This is obviously a greater risk for development of breast cancer than just
over-expression of estrogen receptors."
"In our conditional mice, aromatase provides a double whammy – more estrogen
and more estrogen receptors," Furth noted.
Finally, they tested the effect of local versus systemic estrogen on
development of preneoplasia. The researchers made three comparisons: between
mice in which the ER was over-expressed; mice that had excess estrogen due
to aromatase; and mice that were given more estrogen systemically. "If we
give extra systemic estrogen, we don't see any increased risk of breast
cancer, but the risk increases with extra expression of ER, and is higher
still with local production of aromatase," said Díaz-Cruz. "That suggests
that estrogen production in the breast is an important risk factor for
development of breast cancer."
What these results suggest for women is that if females vary in the amount
of aromatase they naturally produce, as some studies suggest, then women
with higher aromatase levels may be more susceptible to breast cancer, Furth
"Someday we may have a test available that can determine individual
aromatase levels in postmenopausal women so that a preventive aromatase
inhibitor can be prescribed to women at higher risk for breast cancer,"
SOURCE: Cancer Research, published online August 16, 2011