D G Risk Assessment and Management of Women BRCA

November 2009
Risk Assessment and Management of Women
With BRCA Mutations
Kevin S. Hughes, MD, FACS; Veronica Ravnikar, MD, FACOG
uring a routine visit, a
the general population carry a
young single mother
mutation in BRCA1 or BRCA2.1
uidelines from ACOG
tells you that her sister
An estimated 1 in 40 people of
encourage ObGyns
was just diagnosed with breast
Ashkenazi Jewish descent have a
cancer. A new postmenopausal
mutation.1 The estimated lifeto provide breast and
patient reveals that her mother
time risk for breast cancer in
ovarian cancer risk
had breast cancer. These are
women with a BRCA1 or BRCA2
assessment as part of
common scenarios in ObGyn
mutation is 65% to 74%.1
practice, but do you provide
routine clinical practice.
follow-up cancer risk assessIdentifying Patients:
ment and genetic counseling
Clinical Assessment
for hereditary breast and ovarian cancer (HBOC)?
One of the most challenging aspects of risk assessIf not, you may want to consider that ACOG
ment is identifying which patients to test. Not every
guidelines encourage ObGyns to do so as part of
patient should be tested, but those who need testing
routine clinical practice and that the widespread
should receive it. Start by taking a full medical and
availability of genetic testing makes it easier than
family history covering 3 generations (the patient,
ever to provide this valuable service.1
her parents, and her grandparents), using a combination of a written questionnaire and personal consulHBOC Patients Are in Your Practice
tation. Questions to ask include:
Most likely, you have patients with HBOC in
•Breast cancer before age 50?
your practice who need to be identified. It is
•Breast cancer in 2 or more relatives?
estimated that about 1 in 300 to 1 in 800 people in
•Breast cancer in a male relative?
•Breast cancer in both breasts or twice in the
same breast?
Kevin S. Hughes, MD, FACS, is Surgical Director,
•Breast cancer and Ashkenazi ancestry?
Breast Screening, and Co-Director, Avon Comprehensive
Breast Evaluation Center, Massachusetts General Hospital,
•Ovarian cancer at any age?
Boston; Veronica Ravnikar, MD, FACOG, is AssociInclude in the history any relevant environmenate Clinical Professor of Obstetrics and Gynecology and
exposures, risk factors for breast and ovarian
Reproductive Medicine, Harvard Medical School, Boston,
cancer, and surgeries that may have obscured the
and Chair, Department of Obstetrics and Gynecology,
South Shore Hospital, South Weymouth, MA.
hereditary cancer pedigree.
Supported by an educational grant from Myriad Genetics, Inc.
Risk Assessment and Management of Women With BRCA Mutations
To assist in identifying potential candidates for testing,
ACOG provides a detailed list
in the “Criteria for Genetic
Risk Assessment” table in its
guidelines.1 ACOG recommends genetic testing for patients with a greater than 20%
chance of having a BRCA1 or
BRCA2 mutation. For women
with a 5% to 10% or greater
risk, ACOG recommends genetic risk assessment and possible testing.1 Many patients
in your practice meet these
criteria and need to be identified and counseled.
Whether the test
results are positive or
negative, the information
is important and useful to
both the patient and the
health care professional.
Either result leads to
informed development
of critical patient
management strategies.
Discussing the Options
When a patient falls into a group recommended
for testing, it is time to discuss the options. The
conversation might begin like this:
“I recommend a blood test that is usually
covered by insurance that can help you better
understand your risk for hereditary breast and
ovarian cancer, or HBOC. Knowing your risk
can help you take steps to reduce your risk for
these conditions. HBOC is most often caused
by a mutation, or alteration, in either of 2
genes, BRCA1 and BRCA2. Although the risk
for these cancers is high, not everyone with
HBOC syndrome will develop cancer. This test
can help me care for you better and can help
you better care for yourself. Would you like to
hear more about this test?”
Whether the test results are positive or negative, the information is important and useful to
both the patient and the health care professional.2 Either result leads to informed development
of critical patient management strategies.
Medical management options that should be
discussed before testing include an increased
surveillance plan, chemoprevention (tamoxifen,
oral contraceptives), and risk-reducing surgery (mastectomy, oophorectomy).1 It is important to remember that if the patient does not
pursue testing, you and she will still need to
develop a more intensive management strategy
based on her risk level. Testing can help you
The Female Patient Supplement NOVEMBER 2009
both make that strategy
more tailored to her actual
situation. A simple approach
to confirm you have given
complete information is to
read through and discuss
with the patient the “Elements of Informed Consent
for Cancer Susceptibility
Testing” as they appear in
the American Society of
Clinical Oncology guidelines.3 It is also helpful to
provide her with written
information she can share
with relatives.
Going Forward With Testing
Once the decision is made to go forward with testing, it is ideal to initiate testing in an affected
person, whether it is the patient or a family member. If an affected person is not available, testing is
still beneficial.
If you would prefer to refer the patient for
testing rather than manage the process yourself, you can identify a risk assessment clinic
in your area by going to the National Cancer
Institute’s Cancer Genetics Services Directory
Risk assessment and genetic counseling can
be provided by licensed genetic counselors,
medical geneticists, medical oncologists, social
workers, surgeons, oncology nurses, nurse
practitioners, and/or psychologists.4 Many
patients do not follow up with these appointments, however. As the testing information is
essential for effectively managing your patients’
health, consider integrating assessment and
testing into your practice.
Discussion of Test Results
Results of HBOC testing are usually available
in about 2 weeks. Discussion of test results
requires sensitive communications and informed consent. Explain that the test results
are disclosed only to you and that federal
laws prohibit discrimination against patients
who undergo genetic testing. Remind the patient that the test does not detect cancer; it
provides information on inherited risk for cancer.
Possible test results are
positive, negative, or uninformative. Patients will respond
to the results based on their
life circumstances, age, and
cancer mindset. For example,
the young single mother mentioned above may not want to
undergo prophylactic surgery,
whereas the older woman
might welcome it. Of course,
refer patients to an appropriate
counselor if they have problems with the information.
Ideally, all women
at risk for HBOC
would be identified
before cancer develops.
Screening and prevention
strategies could then
be implemented that
could potentially
save lives.
Management of Women
With BRCA Mutations
Ideally, all women at risk for HBOC would be
identified before cancer develops. Screening and
prevention strategies could then be implemented
that could potentially save lives. In addition to
ACOG, the National Cancer Center Network
recommends that women be screened for potential mutations.1,4,5
Currently, women learning that they have a
BRCA mutation fall into 3 broad categories:
unaffected, newly diagnosed with cancer, and
diagnosed with cancer in the past. Management options differ for these groups and include screening with or without chemoprevention or risk-reducing surgery. Management
should be based on age, overall health, and
personal preferences.
A critical element is dissemination of risk information to as many family members as possible. Once a carrier is identified, a concerted
effort should be made to identify every other
carrier in the family.
Options for Unaffected Women
Surgery. Prophylactic bilateral total mastectomy is the most effective strategy for prevention
of breast cancer, offering a 95% reduction in
risk. Nipple-sparing mastectomy may be an option and is currently under investigation. Nipple-sparing mastectomy is not to be confused
with subcutaneous mastectomy, which leaves behind a
large amount of breast tissue
and is not considered acceptable for prophylaxis.
Screening With or Without
Chemoprevention. For those
who opt against prophylactic mastectomy, screening
is essential, with or without
chemoprevention. Screening
should include monthly breast
self-examination and, starting
at age 25, clinical examinations, annual mammograms, and annual magnetic
resonance imaging (MRIs).
Tamoxifen has been shown to decrease risk
for breast cancer in high-risk women; raloxifene has similar effects but is indicated only for
postmenopausal women. Neither has been
proved effective in the BRCA carrier population; however, it is reasonable to discuss these
in addition to screening.
In premenopausal women, prophylactic bilateral salpingo-oophorectomy (BSO) significantly reduces risk for both breast and ovarian cancer.
Surgery. W hereas mastectomy is optional,
BSO is essential. As effective screening modalities are not available for ovarian cancer,
BSO is strongly recommended after age 35,
once childbearing is complete.
Screening With or Without Chemoprevention.
Twice-yearly transvaginal ultrasound and
CA-125 testing should be done starting at age
35 (or earlier if appropriate) until the ovaries are
removed. A note of caution: This strategy has
unproven efficacy but is still recommended.
Oral contraceptives have been demonstrated
to reduce risk for ovarian cancer in the general
population, as well as in women who carry
BRCA mutations. The small potential risk for
breast cancer should be considered, though the
benefit most likely outweighs the risk. In smokers, morbidly obese women, and women older
The Female Patient Supplement November 2009 Risk Assessment and Management of Women With BRCA Mutations
than 40, there may be more
risk than benefit.
There are still
Discussion of genetic risk
and genetic testing is an
an inordinate number of
Options for Patients
integral part of ObGyn
Newly Diagnosed
clinical care. There is subBRCA carriers who are
With Cancer
stantial benefit to identifyunaware of their status,
The BRCA carrier must choose
ing BRCA1 and BRCA2 carmany of whom are cancer
between breast conservation
riers, as there is a plethora
and bilateral mastectomy. Overof management options that
survivors. Identification
all, while bilateral mastectomy
can decrease the morbidity
of these women and their
is likely the most appropriate
and mortality of disease.
procedure, it is not proved supeIdentifying carriers and
families has substantial
rior, and many women are not
instituting these strategies
ready to take this step so soon
can be lifesaving. It is critinot be overlooked.
after being diagnosed as a carcal to leverage the status of
rier. If lumpectomy is chosen,
each carrier for the maxiMRI should be done before
mal family benefit by testsurgery. If childbearing is complete, oophorectomy
ing as many family members as possible.
is recommended, as it will markedly decrease the
Acknowledgment: The authors would like to
risk for ovarian cancer and may have a role as
acknowledge Constance Roche, MSN, RN, CS,
an adjuvant treatment in premenopausal women
for her critical review of this manuscript.
with estrogen receptor–positive cancer. The
BRCA carrier with newly diagnosed ovarian
Disclosures: Dr Hughes is a member of the
cancer should undergo a complete course of
speakers bureau of Myriad Genetics. Dr
therapy and then, based on her prognosis,
Ravnikar is a member of the speakers bureau
begin a commensurate level of breast screening.
and a consultant of Teva Pharmaceuticals.
Prophylactic mastectomy should be considered
with caution.
Patients Diagnosed With Breast or
Ovarian Cancer in the Past
There are still an inordinate number of BRCA
carriers who are unaware of their status, many of
whom are cancer survivors. Identification of
these women and their families has substantial
benefit and should not be overlooked. Management decisions should be based on cancer history,
prognosis, and prior treatment.
The patient who has had breast cancer and
whose prognosis is good should be managed
similarly to the unaffected woman, based on remaining organs. Bilateral mastectomy is appropriate if she prefers. Oophorectomy is suggested
once childbearing is complete. Ovarian screening
until the ovaries are removed is appropriate. The
patient who has had ovarian cancer and whose
prognosis is good should be managed similarly to
the unaffected woman.
The Female Patient Supplement NOVEMBER 2009
1. A merican College of Obstetricians and Gynecologists; ACOG
Committee on Practice Bulletins—Gynecology; ACOG
Committee on Genetics; Society of Gynecologic Oncologists.
ACOG practice bulletin no. 103: hereditary breast and ovarian
cancer syndrome. Obstet Gynecol. 2009;113(4):957-966.
2. Berliner JL, Fay AM; Practice Issues Subcommittee of the
National Society of Genetic Counselors’ Familial Cancer
Risk Counseling Special Interest Group. Risk assessment and
genetic counseling for hereditary breast and ovarian cancer:
recommendations of the National Society of Genetic Counselors. J Genet Couns. 2007;16(3):241-260.
3. A merican Society of Clinical Oncology. American Society
of Clinical Oncology policy statement update: genetic
testing for cancer susceptibility. J Clin Oncol. 2003;21(12):
4. National Cancer Center Network. Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment:
Breast and Ovarian. Available at: www.nccn.org/professionals/
physician_gls/PDF/genetics_screening.pdf. Accessed
August 8, 2009.
5. Schwartz GF, Hughes KS, Lynch HT, et al. Proceedings of
the International Consensus Conference on Breast Cancer
Risk, Genetics, & Risk Management, April, 2007. Cancer.