Download The High Risk Breast Cancer Clinic

Making Sense of Genetic Testing for
Cancer-Causing Mutations
The High Risk
Breast Cancer Clinic
at Huntsman Cancer Institute
Women Needed for New Research Study
Upcoming Questionnaire
Vice President Biden Visits Huntsman
Cancer Institute
SUMMER 2016
Recruitment of the Next Generation Begins
HOW TO REACH US
801-585-3525
1-800-936-6343 toll free
801-585-5763 fax
www.huntsmancancer.org
For genetic counseling services
at Huntsman Cancer Institute,
contact the Family Cancer
Assessment Clinic.
www.huntsmancancer.org/fcac
801-587-9555
As part of the National Cancer Institute’s additional funding to the Breast
Cancer Family Registry (BCFR; see story on page 3), we will be contacting
the younger adult members of families currently enrolled in the BCFR. We
have a large resource of data, blood, and tissue samples from adults in many
families, and through the LEGACY study we have similar data on young girls
in the families.
In order to better understand the causes, prevention, and treatment of cancer,
we would like to add the “in-between” generation in our registry, including
younger adults between the ages of 20 and 40. Over the next few months,
we will be in touch with these members of some of your families. We are
optimistic this will provide important knowledge to advance cancer prevention
and treatment, and that it will be a productive experience for those who
choose to participate.
For a referral to genetic
counselors in your area,
contact the High Risk Breast
Cancer Clinic.
801-585-3525
1-800-936-6343 toll free
To locate genetic counseling
services in your area, visit
these websites:
National Society of
Genetic Counselors
www.nsgc.org
National Cancer Institute
www.cancer.gov/search/genetics
services
Making Sense of Genetic Testing for Cancer-Causing Mutations
who have panel testing will often be told that they have a
VUS in one of the newer genes. Investigators are much less
certain about how these changes affect the risk for cancer.
Scientists can ask several questions to try to classify a VUS
as either deleterious or benign:
• Is the VUS tracking with cancer in the family?
If all or most members of the family with cancer also
have the variant, it is more likely that it is significant,
as opposed to a family where many individuals with
cancer do not have the variant.
Many genes have been linked to an increased risk of breast
cancer. The most understood of these are BRCA1 and
BRCA2 (short for breast cancer 1 and 2), but we now know
there are 20 or 30 genes that, when altered (mutated),
increase the risk of breast cancer. Several companies offer
tests for many of these genes, usually in “panels” that test
for many genes at the same time.
The genes that have been more recently discovered have
not been as extensively studied as BRCA1 and BRCA2. In
contrast to BRCA1 and BRCA2, where the risks of breast
and ovarian cancer are both known to be high, the risks in
people with a mutation in the recently discovered genes is
not known. Mutations in some genes may increase the risk
of ovarian cancer but not breast cancer. Some genes that
increase the risk for breast cancer may increase it by only a
small amount.
In a recent paper published in the New England Journal of
Medicine, David Goldgar, PhD, and Sean Tavtigian, PhD,
of Huntsman Cancer Institute (HCI) and their colleagues
concluded that a clinically important increased risk of
cancer had been shown for only a few of the 20–30 nonBRCA genes on most of these panel tests.
Another factor that further confuses gene panel test
results is that inherited changes in the newer genes may be
identified for which the significance is unclear. “Variants of
uncertain significance” (VUS) in the BRCA genes have been
studied for many years, so investigators now understand
which of these actually increase the risk of cancer and which
do not.
In other words, most VUS in BRCA genes have been
reclassified as either deleterious (those that increase the risk
of cancer) or benign (those that do not). However, people
• How common is the VUS in people without cancer?
If the particular variant is found in many people
without cancer, it is less likely to be significant. This
information will be available when more people are
tested using gene panels.
• Does the VUS in the gene cause a change in an
important part of the protein? Some parts of the
protein made from the gene are more important than
others. Gene changes that occur in crucial parts of the
protein are more likely to be cancer-causing.
• How well do cells with the gene variant function
compared to normal cells?
• Does the VUS occur in the same part of the gene
across many species? One interesting fact in biology is
that similar genes are found in fish, frogs, birds, mice,
other mammals, and humans. If the gene change is in
a part of the gene that is otherwise the same in all these
species, it is more likely that it is harmful and increases
the risk of cancer.
The bottom line for families in the High Risk Breast Cancer
Clinic who have a VUS is that genetic testing results
alone do not allow for determining who is at higher risk
to develop cancer and who is not. Variants do not give
clear information about cancer risks, which means they
are unreliable for medical management recommendations.
Instead, family history is the basis for determining cancer
risk in individuals in VUS families. Laboratories studying
VUS notify us when a VUS is reclassified. In turn, we let
participants know of that change in classification.
Hopefully, enough progress will soon be made to better
understand variants so our participants have a clearer
understanding of their risk of developing cancer.
— page 2 —
Women Needed for New Research Study
Huntsman Cancer Institute, the Abramson Cancer Center at
the University of Pennsylvania, and Memorial Sloan-Kettering
Cancer Center in New York are recruiting more than 2,000
women for a study titled “MRI Background Parenchymal
Enhancement as a Risk Factor for Breast Cancer: The
IMAGINg and Epidemiology (IMAGINE) Study.”
This study compares MRIs from normal breasts of women
who have cancer in the opposite breast and MRIs of
breasts in women who do not have cancer. Investigators
are hoping in the future they can predict the risk of getting
breast cancer by looking at breast tissue characteristics on
MRI. The investigators will also compare the information
collected from questionnaires and medical records to help
better understand how this may affect the risk of developing
breast cancer. If a saliva or tissue sample is collected for
future use, this information will allow investigators to study
genetic risk factors as well.
Women between 21 and 69 years old who have had a
breast MRI in the past five years may be able to participate.
Involvement includes completing a brief questionnaire,
giving permission for study investigators to review copies of
MRIs and mammograms, and providing an optional saliva
sample to be used for future studies.
To learn more about the IMAGINE Study, contact:
Karen O’Toole
801-581-8795
[email protected]
Cathy Ricci
801-585-7526
[email protected]
Upcoming Questionnaire
In 2012, the National Cancer
Institute provided five years of
additional funding for the High Risk
Breast Cancer Clinic/Breast Cancer
Family Registry (HRBCC/BCFR),
which was originally funded in 1994.
A portion of the new funding was
set aside for the development of a
questionnaire that will help clarify the
risk factors for cancer and examine the
type of screenings and surgery chosen
by women in the HRBCC.
During the past year, six BCFR sites
nationwide have worked collectively
to develop the questionnaire so we
can meet the funding goal. The Utah
BCFR site at Huntsman Cancer
Institute recently received approval
from the University of Utah’s ethics
review board to begin sending the
questionnaire to eligible female
participants. This spring we plan to
send batches of approximately 100
questionnaires each month and hope
to complete all mailings by spring
2017. If the response
to the mailing goes
well, we may finish the
process sooner.
You can help by
completing the
questionnaire soon
after receiving it
and returning it in
the postage-paid
envelope provided by
the study. Although
the questionnaire may seem long,
there are several sections that do not
apply to everyone, so please read
the instructions carefully to avoid
answering unnecessary questions.
Also, several questions ask for a select
number of responses: for example,
we will ask that you pick your best
two or three choices from a list of
multiple options. Please be careful
not to select more or less than the
requested number. We will include a
date on page 1 of the questionnaire
— page 3 —
that refers to the last time you completed
a questionnaire for us. This will be called
your “Reference Date.” When you see
“Reference Date” in the questionnaire,
simply refer to the date on page 1.
As in the past, we will include our
contact information and encourage
you to contact us with concerns or
questions. Thank you for your continued
participation.
Vice President Biden Visits Huntsman Cancer Institute
As part of his plan to hear from academic, biotech, and
pharmaceutical leaders around the country, Vice President
Biden visited Huntsman Cancer Institute (HCI) February
26, 2016. During his visit, HCI leaders discussed, among
other items, three topics related to the Cancer Moonshot
(and which are also of interest to our HRBCC participants):
• High-risk clinics, which allow us to provide precise cancer
detection and prevention to individuals at risk for cancer
• Outreach to provide cancer education, including genetic
counseling and testing, and cancer care to patients in
rural and frontier areas
Huntsman Cancer Institute
2000 Circle of Hope, Room 1146
Salt Lake City, Utah 84112
During his 2016 State of the Union address, President Obama
asked Vice President Joe Biden to lead the “National Cancer
Moonshot” initiative. The Cancer Moonshot has set a goal to
achieve ten years’ progress against cancer in the next five years.
This will include better prevention and detection of cancer and
will make more effective treatment available to more patients.
RETURN SERVICE REQUESTED
From left: HCI’s Jewel Samadder, MD; Vice President Biden;
Jon Huntsman, Jr.; Utah Senator Orrin Hatch
• The Utah Population Database, which links genealogical
records to cancer registry and electronic medical records
to create a database of more than 8 million individuals.
This database was used to discover many cancer
predisposition genes, including BRCA1 and BRCA2
SALT LAKE CITY, UTAH
PERMIT NO. 1529
PAID
NONPROFIT ORGANIZATION
U.S. POSTAGE