|Decrease in Breast Cancer Rates Related to Reduction
in Use of Hormone Replacement Therapy
The sharp decline in the rate of new breast cancer cases in 2003
may be related to a national decline in the use of hormone replacement
therapy (HRT), according to a new report in the April 19, 2007,
issue of the New England Journal of Medicine. The report
used data from the Surveillance, Epidemiology and End Results (SEER)
program of the National Cancer Institute (NCI), part of the National
Institutes of Health.
Age-adjusted breast cancer incidence rates in women in the United
States fell 6.7 percent in 2003. During this same period, prescriptions
for HRT declined rapidly, following highly-publicized reports from
the Women’s Health Initiative (WHI) study that showed an increased
risk of breast cancer, heart disease, stroke, blood clots, and
urinary incontinence among postmenopausal women who were using
hormone replacement therapy that included both estrogen and progestin.
The two most commonly prescribed forms of HRT in the United States,
Premarin® and Prempro, had their steepest declines starting
in 2002-2003 — from 61 million prescriptions written in 2001
to 21 million in 2004.
Led by senior investigator, Donald Berry, Ph.D., of the University
of Texas M.D. Anderson Cancer Center, Houston, Texas, the research
team showed that the decrease in breast cancer incidence began
in mid-2002 and leveled off after 2003. Comparing rates from 2001
and 2004 showed a decrease in annual age-adjusted incidence of
8.6 percent. The decrease occurred only in women over the age of
50 and was more evident in women with cancers that were estrogen
receptor (ER) positive — tumors that need estrogen in order
to grow and multiply. The speed at which breast cancer rates declined
after the WHI announcements may indicate that extremely small ER-positive
breast cancers may have stopped progressing, or even regressed,
after HRT was stopped.
“Breast cancer is the most frequently diagnosed cancer among women
in the United States, and we have made great strides in its treatment,” said
NCI Director John E. Niederhuber, M.D. “Still, we don’t know all
the causes of breast cancer, and breast cancer rates had been increasing
for two decades up to 2002. Finding the simple ways, such as limiting
HRT use to decrease breast cancer risk, is a step forward.”
Preliminary findings of this report were presented at the 29th
annual San Antonio Breast Cancer Symposium in 2006. Data from 2004,
which was of great interest to those present for the meeting, were
not available at that time. This report now includes the data from
2004, which show a leveling-off of breast cancer incidence from
2003 to 2004. This observation, combined with a stabilization of
HRT use in 2004, further strengthens the association between breast
cancer incidence and use of HRT.
Understanding the effect of cessation of HRT may be complex. Effects
may vary depending on the type of HRT used and other factors specific
to how the hormones affect the body. From the data in this report,
it seems that the decline in breast cancer incidence that is related
to a nationwide decline in use of HRT may have has run its course,
and breast cancer incidence rates may stabilize or even begin to
rise again. Researchers do not yet know if this reduction in HRT
use will have a long-term effect on rates, or whether reduction
in hormone levels simply slowed the growth of clinically detectable
tumors, in which case as HRT use stabilizes, breast cancer incidence
will begin to rise again.
Several other possibilities were considered to explain the sudden
decrease in new breast cancer cases, including changes in reproductive
factors, rates of mammography screening, environmental exposures,
and changes in diet. HRT was the only risk factor that changed
substantially from 2002 to 2003 and provides a possible explanation
for this trend. “Recent reports have suggested a small decline
in mammography use after 2000,” said Kathy Cronin, Ph.D., of the
Surveillance Research Program at NCI. “Screening may play a role
as well, and the contribution of mammography to the observed decline
in incidence is currently being investigated.”
Because this analysis is based on population statistics, the study
does not prove a link between HRT and breast cancer incidence.
Only a randomized clinical trial could prove causation. When the
link between breast cancer and HRT was first confirmed in the WHI,
which was a randomized clinical trial, women in the study were
asked to discontinue their study medications (either placebo or
hormones), and were encouraged to continue undergoing annual mammography.
These women are still being followed, and the WHI researchers are
expected to release a follow-up report later this year about the
group who received HRT (estrogen and progestin) later this year.
This report will provide a much higher level of evidence about
the influence of HRT (and cessation of HRT) on the incidence of
“The decision about use of HRT is complex,” says study researcher
Christine Berg, M.D., from the National Cancer Institute. “While
HRT provides relief from the symptoms of menopause, it may also
increase one’s risk of breast cancer. It is important that women
meet with their doctor to discuss what decision is right for them,
particularly if they are at high risk for breast cancer.”
For information on NCI’s Surveillance, Epidemiology, and End Results
(SEER) Program, please go to http://seer.cancer.gov/.
For more information about cancer, visit http://www.cancer.gov,
or call NCI's Cancer Information Service at 1-800-4 CANCER.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
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