Breast cancer drop linked to hormone therapy decline The malignancy rate is
not caused by a reduction in mammography use, as scientists had speculated,
new research concludes.
By Thomas H. Maugh II
Times Staff Writer

July 25, 2007

Patient treatment records from a large HMO show that the recent decline in
breast cancer rates is linked to a sharp drop in use of hormone replacement
therapy and not to reductions in the percentage of women getting mammograms,
as many scientists had speculated, researchers said Tuesday.

Dr. Andrew G. Glass and his colleagues at Kaiser Permanente Northwest in
Portland, Ore., found a drop in breast cancer rates among their patients
from 2003 to 2006 even though mammography rates remained virtually constant,
they reported in the Journal of the National Cancer Institute.

A lowered mammography rate results in fewer breast cancers detected.
Researchers are not sure why the rate declined, but contributing factors
include the closing of some mammography centers, the cost, the discomfort
and fewer visits to doctors' offices because of the drop in hormone
replacement therapy.

By using a patient population for whom the mammography rate remained
constant, "we were able to disentangle mammography from hormones," Glass

In an editorial in the same journal, Dr. Donald A. Berry and Dr. Peter M.
Ravdin of the University of Texas M.D. Anderson Cancer Center in Houston
agreed that a reduction in mammography use could not be responsible for the
bulk of the decline in breast cancer.

"The only known factor that would seem to explain the precipitous drop in
incidence is the sharp decrease in use of menopausal hormone therapy," they

No one is suggesting that estrogen triggers the formation of breast tumors.
Rather, most researchers think it accelerates growth of existing tumors.
Stopping hormone replacement therapy slows the growth of small tumors,
delaying their detection for perhaps a couple of years and producing an
apparent decline in incidence, Berry and Ravdin speculated.

Prescriptions for estrogen and progestin fell by nearly half in 2003 after
2002 results from the Women's Health Initiative, a National Institutes of
Health program, linked an increased breast cancer risk to hormone
replacement therapy.

Nearly 40% of post-menopausal women had used the hormones to ease menopausal
symptoms, such as hot flashes, and to prevent conditions related to aging,
including osteoporosis.

Berry, Ravdin and their colleagues reported last year that breast cancer
rates fell 7% in 2003, attributing the decline to decreased use of hormone
therapy. A report this year showed that by the end of 2004, the incidence
had dropped 11.8% among women over 50, the primary recipients of hormone

But an analysis earlier this year by epidemiologist Ahmedin Jemal and his
colleagues at the American Cancer Society concluded that the decline in
breast cancer had begun in 1999 and that a significant fraction of the
decrease could be attributed to a 4% drop in mammography rates over the
period in question.

Jemal wrote that Kaiser's figures on mammography differed from national
figures and questioned Glass' conclusion that the drop in hormone usage was
the most important factor in the breast cancer rate decline. "All you can
say is that their data is suggestive," he said.

Glass and his colleagues reviewed the histories of 7,386 women diagnosed
with invasive breast cancer and treated at Kaiser Permanente Northwest from
1980 through 2006.

They concluded that breast cancer rates rose 26% from the early 1980s to the
early 1990s, rose an additional 15% to 2002 , then dropped 18% from 2003
through 2006.

The initial rise occurred in concert with sharp increases in mammography
rates and the rise of hormone replacement therapy. During that period, the
use of mammography grew from just a few percent of patients to about 75% of
all older women.

The 15% increase in breast cancer rates from 1992 to 2002 paralleled a
continued rise in hormone replacement therapy, while mammography rates
remained at the 1991 level.

The sharp drop in breast cancer rates starting in 2003 occurred in concert
with a 75% drop in hormone use among the Kaiser patients, while mammography
rates remained at 1991 levels. By the end of 2006, they found, the breast
cancer rate  126.2 cases per 100,000 women  was the lowest since the

The bulk of the change over the years was in the so-called
estrogen-receptor-positive tumors, whose growth is stimulated by estrogen.
These tumors account for 70% to 80% of all breast cancers.

The Kaiser data showed that the estrogen-receptor-negative tumors did not
experience the increase seen for the receptor-positive tumors during the
1980s and 1990s. They did, however, drop sharply from 2003 to 2006, for
reasons that are unclear.

Amos Pines, president of the International Menopause Society, noted,
however, that Glass' data showed a decline in breast cancer beginning in
1999 similar to that of Jemal's data. "There must be another, non-hormonal
and still unknown factor explaining, at least in part, these changes in

Long-term therapy may be associated with a small increase in risk, but "in
women younger than 60, hormone therapy," particularly estrogen alone, he
concluded, "is safe."


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Michael Balter
Contributing Correspondent, Science
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