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A review of several studies finds that experts have likely overestimated the risk of
breast cancer in women who carry certain genetic predispositions to the disease.
Previously studies have found that women who have genetic mutations of BRCA1 (breast cancer gene 1) or BRCA2 (breast cancer gene 2) have a 70% to 85% risk of
developing breast cancer by age 70. However, the authors of the new analysis say those
estimates are flawed because the women in those studies had other factors (such as strong
family histories) that put them at higher risk of breast cancer than the average woman
with a BRCA gene mutation. The analysis may be important for all women considering have
preventive breast removal surgery or taking other options because they believe they are at
high risk for developing breast cancer.
BRCA1 and BRCA2 are two tumor suppressor genes that, when functioning normally, help
repair damage to DNA—a process that also prevents tumor development. In 1994,
researchers discovered that women who carry mutations of BRCA1 or BRCA2 are at higher risk
of developing both breast and ovarian cancer than women who do not have these genetic
mutations. Women with BRCA1 mutations account for 5% of all breast cancer cases.
Genetic testing is available to women with strong family histories of breast cancer or
other risk factors. These tests can determine whether a woman is carrying BRCA gene
mutations. Women who test positive for the BRCA gene mutations sometimes opt to have their
breasts removed as a preventive measure, a procedure called prophylactic mastectomy. This surgery has been
shown to reduce the risk of breast cancer by 90% since most all of the breast tissue is
removed. Other preventive options for women at high risk of breast cancer include taking
the drug tamoxifen (brand name, Nolvadex) for a period of
five years, being closely monitored by physicians with mammography
and/or other imaging tests, and in some cases, having the ovaries removed (prophylactic oophorectomy).
However, Colin B. Begg, PhD, of Memorial Sloan-Kettering Cancer Center, worried that
women may be making drastic decisions to prevent breast cancer based on genetic counseling
that presents skewed data about their true risk of developing the disease. Dr. Begg
analyzed eight studies that estimated breast cancer risk in women with BRCA gene mutations
to determine whether their findings were flawed.
His analysis found that the risk of developing breast cancer is not only associated
with genetic factors, such as BRCA gene mutations, but with several other factors.
Notably, many women who participated in the reviewed BRCA gene studies had very strong
family histories of breast cancer (i.e., their mothers and sisters had been diagnosed with
the disease). According to Dr. Begg, including these women in the studies led to
overestimating breast cancer risk because these women likely shared environmental or other
genetic factors that put them at higher risk than other women with BRCA gene mutations.
"A sample of women who have been diagnosed with breast cancer who are identified
as mutation carriers are more likely to also have other breast cancer risk factors than
similar mutation carriers who are disease-free," wrote editors Linda Wang and
Katherine Arnold in an accompanying news statement in the Journal of the National
Cancer Institute. As Dr. Begg explained, "The current strategy for estimating
[breast cancer risk from BRCA gene mutations] is unbiased only if all carriers share an
identical risk of developing the disease."
As Wylie Burke, MD, PhD, and Melissa A. Austin, PhD, of the University of Washington in
Seattle wrote in an accompanying editorial, many studies fail to address the complexity of
diseases such as breast cancer. Knowing a woman carries a BRCA gene mutation does not
completely define her risk of developing breast cancer, argue Dr. Burke and Dr. Austin.
Moreover, many studies do not account for risk modifiers, such as diet and exercise, which
can have a significant effect on reversing genetic predisposition to illnesses such as heart disease.
Thus, Dr. Begg believes that women should be aware that their risk of breast cancer
from BRCA gene mutations may be lower than what has been presented in the past. Therefore,
less invasive methods (such as the drug tamoxifen) may be preferred over complex
procedures such as prophylactic mastectomy.
Additional Resources and References
- The study, "On the Use of Familial Aggregation in Population-Based Case Probands
for Calculating Penetrance," is published in the August 21, 2002 issue of the Journal
of the National Cancer Institute. The accompanying editorial by Dr. Burke and Dr.
Austin, as well as the news statement by Wang and Arnold, are also available in the same
journal issue: http://jncicancerspectrum.oupjournals.org/jnci/
- To learn more about BRCA gene mutations, please visit http://www.imaginis.com/breasthealth/genetic_risks.asp
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