The National Comprehensive Cancer Network (NCCN) has implicated
several additional mutations when planning risk management strategies in
patients with hereditary breast and ovarian cancer. These mutations confer a
risk of either or both cancers with relatively high penetrance.
Dr. Tuya Pal MD, from
the Moffitt Cancer Center, Tampa, Florida said “ the recent discovery that the
genetic mutation PALB2 is associated with an aggressive form of breast
cancer, as well as the realization that the newer ovarian cancer genes RAD51C,
RAD51D, and BRIP1 pose an added lifetime risk for ovarian
cancer, should prompt physicians to discuss possible prophylactic procedures
with patients who are found to carry these mutations” at 21st Annual
National Comprehensive Cancer Network (NCCN) conference in Hollywood, FL.
It is known that women who have BRCA1 carriers have
a 55 to 65 percent chance of developing breast cancer and 35 to 70 % chance of
developing ovarian by age 70 and the corresponding numbers for BRCA2 carriers are 45% and 10-30% respectively. Women with Lynch syndrome have around
10% chance of developing ovarian cancer. The researchers at the conferences
implicated additional mutation BARD1, BRIP1, RAD51C, RAD51D and
PALB2 with similar level of evidence as BRCA1/2 for ovarian cancer.
Together with established Ovarian Cancer (OC) genes, this
addition bring the total number of genes suspected to cause hereditary OC to
11.
Till now, the NCCN was advising or recommending risk
reduction surgery of salpingo-oophorectomy as a part of preventive strategy in
BRCA1/2 mutation carrier. According to National Cancer Institute( NCI) the
lifetime risks of ovarian cancer are 5.2% in RAD51C mutation carriers,
5.8% in BRIP1 mutation carriers, and 12% in RAD51D mutation
carriers; risk-reducing salpingo-oophorectomy (RRSO) may be considered for
these patients upon completion of childbearing.
Screening for these genes is specifically important in
regards to Ovarian cancer as there are no screening test and diagnostic
modalities at present to catch the disease at an early stage.
A family history should always be taken into account and
with strong family history; prophylactic risk management in the form of oophorectomy
should be considered.
PALB2 is also an important genetic mutation added to
the list along with PTEN, and PT53 that causes the Breast cancer. Women with
an abnormal PALB2 gene have a 14% risk of developing breast cancer by age 50
and a 35% risk of developing breast cancer by age 70. It is also seen that
cancers developing in patients with the genetic mutation PALB2 are
very aggressive and in a polish study survival for women with breast cancer and a PALB2
mutation was 48·0% compared with 74·7% for patients without a mutation.
So, genetic testing at this point of time has become an
important part of cancer management, because if we are proactive we can
diagnose the cancer at very early stage or prevent it altogether if we know our
risk for them.
Much progress has been made in the field of genetic testing
with increased use of multi-gene testing. Genetic testing allow the patients to
make an informed decision, about there course of treatment, prognosis and any
other cancer risks due to genetic mutation.
The updated NCCN Guidelines for Women with Mutations in
PALB2, ATM, CHEK2, BRIP1, RAD51C, and RAD51D
Annual
MRI beginning at age 30 or earlier, based on family breast cancer history for
women with mutations in following genes: ATM, CHEK2 and PALB2
Discussing the option of risk-reducing mastectomy for women with mutations in: PALB2
3) Ovarian Cancer Risk Management
Women
with mutations in following genes should consider risk-reducing removal of
ovaries and fallopian tubes: BRIP1, RAD51C and RAD51D.
References:
Contribution of
Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in
the Population JCO
(2015) 33 (26):
2901-2907
A genetic testing for breast cancer gene is a blood test that checks to see if you have a genetic mutation that may increase your risk for breast and ovarian cancer.
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