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Benefit of
Cancer Prevention Surgery differs between
women with BRCA1 and BRCA2 mutations
Newswise — The surgical removal of the
ovaries has been widely adopted as a
cancer-risk-reducing strategy for women with
either BRCA1 or BRCA2 mutations.
A
new multicenter study led by researchers at
Memorial Sloan-Kettering Cancer Center (MSKCC)
is the first prospective examination of the
impact of this procedure in which BRCA2
mutation carriers were analyzed separately
from BRCA1 mutation carriers.
All previous studies evaluating this
approach have only examined BRCA1 and BRCA2
mutation carriers together or have limited
their analysis to BRCA1 mutation carriers
alone.
The findings of the new study, to be
published in the March 2008 issue of the
Journal of Clinical Oncology, may have
important implications for women comparing
the risks and benefits of specific
cancer-risk-reduction options.
According to the research, the surgery –
called risk-reducing salpingo-oophorectomy (RRSO)
– may confer different benefits for women at
inherited risk for breast and ovarian cancer
depending upon whether BRCA1 or BRCA2 is
abnormal.
The efficacy of this procedure for the
prevention of breast and gynecologic cancer
had never been evaluated in groups of women
stratified according to mutation type,
despite 17 percent to 39 percent of all BRCA
mutation carriers having a mutation in the
BRCA2 gene.
“These findings will allow doctors to better
tailor risk-reduction approaches for women
at inherited risk for breast and ovarian
cancer,” said the study’s lead author, Noah
Kauff, MD, a gynecologist and geneticist at
MSKCC.
“Given
these results, further studies evaluating
the efficacy of risk-reduction strategies in
BRCA mutation carriers will likely need to
stratify by the specific gene mutated,” he
added.
Researchers compared the incidence of breast
and gynecologic cancers between a group of
509 women 30 years of age or older who
carried a BRCA1 or BRCA2 mutation and had
undergone RRSO, and a group of 283 women
with these mutations who did not have the
surgery.
The women were followed prospectively for
three years via questionnaire and medical
record review.
Investigators found that RRSO was associated
with a 72 percent breast cancer risk
reduction in women with BRCA2 mutations –
nearly twice the reduction in breast cancer
risk compared to women with BRCA1 mutations.
The
surgery also reduced the risk of gynecologic
cancer by 85 percent in women with a BRCA1
mutation. While protection against
gynecologic cancer was suggested in women
with a BRCA2 mutation, researchers were not
able to estimate the level of reduced risk
due to the low incidence of gynecologic
cancers among women with these mutations.
Further analyses demonstrated that RRSO
appeared to reduce the risk of estrogen
receptor (ER)-positive breast cancer by 78
percent in women with a mutation in either
BRCA1 or BRCA2, but had no effect on the
development of ER-negative breast cancers.
Because BRCA1 carriers are more likely to be
diagnosed with ER-negative breast cancers,
the authors note that carriers of these
mutations need to consider additional
breast-cancer-risk-reduction strategies,
such as intensive screening with breast MRI
or prophylactic mastectomy.
“While our results suggest that removal of
the ovaries in women with BRCA1 or BRCA2
mutations is highly protective against
ER-positive breast cancers, further research
is urgently needed to develop effective
non-surgical prevention strategies for the
ER-negative cancers that are frequently
associated with these mutations,” said Dr.
Kauff.
Researchers from the following institutions
also contributed to this study: University
of Pennsylvania, Philadelphia, PA;
Dana-Farber Cancer Institute, Boston, MA;
Lombardi Comprehensive Cancer Center,
Washington, DC; Manchester Regional Genetics
Service, Manchester, United Kingdom;
Creighton University School of Medicine,
Omaha, NE; The Institute of Cancer Research,
Sutton, United Kingdom; University of
California at Irvine, Irvine, CA; Fox Chase
Cancer Center, Philadelphia, PA; Yale
University, New Haven, CT; and
Baylor-Charles A. Sammons Cancer Center,
Dallas, TX.
This work was partially supported by the
Department of Defense Breast Cancer Research
Program, the US Public Health Service,
Cancer Research UK, the Lucius N. Littauer
Foundation, the Frankel Foundation, the
Genet Fund, the Koodish Fellowship Fund, the
Project Hope Fund for Ovarian Cancer
Research and Education, QVC Network, the
Fashion Footwear Association of New York,
the Edward Spiegel Memorial Fund, revenue
from Nebraska cigarette taxes awarded to
Creighton University by the Nebraska
Department of Health and Human Services, the
Charles F. and Mary C. Heider Chair in
Cancer Research at Creighton University, the
University of Pennsylvania Cancer Center,
and the Prevention, Control, and Population
Research Program of MSKCC.
MSKCC is the world’s oldest and largest
private institution devoted to prevention,
patient care, research, and education in
cancer.
Our scientists and clinicians generate
innovative approaches to better understand,
diagnose, and treat cancer. Our specialists
are leaders in biomedical research and in
translating the latest research to advance
the standard of cancer care worldwide. For
more information, go to
www.mskcc.org.
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