October 21, 2025 • 42 mins
For Breast Cancer Awareness Month, Dr. Susan Domchek joins the show to talk about the importance of knowing your genetic history, using genetic testing to understand cancer risk, and what you can do if you learn that you have BRCA gene mutation.
Links to resources mentioned in this episode:
National Society of Genetic Counselors
National Comprehensive Cancer Network
Note: In this show, we use “women” as shorthand for people with XX chromosomes. We understand sex and gender are more complex, and acknowledge the experiences we describe reach beyond that word.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:17):
Pushkin.
Speaker 2 (00:24):
This show is not a substitute for professional medical advice, diagnosis,
or treatment. It is for informational purposes. Please consult your
healthcare professional with any medical questions.
Speaker 1 (00:37):
My mom was diagnosed with breast cancer in her fifties. Luckily,
it wasn't complicated and she quickly went into remission. But
this April, she was diagnosed with pancreatic cancer, one of
the most lethal and hardest cancers to treat. It was
devastating news. I assumed it wasn't a hereditary cancer. Most aren't,
but some cancers can be caused by genetic mutations like
(01:01):
the Brca one and Brca two genes, sometimes referred to
as the Braca genes. These are genes that normally protect
cells from damage, but when they don't work, cancerous skyrockets.
Years ago, I was actually testing myself for Brocca mutations.
I sent off blood work for genetic testing with a
private company. I never got the results back, and I
(01:23):
sort of forgot about it. That is until my mom's
doctors tested her blood and found out that she carried
a Broco one mutation. Her cancer had a genetic heritable element.
I contacted the testing company that I had sent my
blood work to years earlier, and I finally got those results.
(01:44):
I was positive for a BRCA one mutation. Myself, I
would have been livid. If I wasn't so scared. I'd
already had my own battle with HPV related cancer in
twenty twenty one, and as a pelvic surgeon, I know
too well the realities of ovarian cancer. Within weeks, I
had my ovaries and fallopian tubes removed. The wildest part.
(02:07):
I have a PhD in genetics. I worked with some
of the best vision icians and scientists in the world.
I am an expert in ovarian cancer, yet this potentially
fatal mutation when undetected in me for nearly sixty three years.
I'm doctor Elizabeth Pointer. And this is Decoding Women's Health,
(02:27):
a show from Pushkin Industries and the Atria Health Institute.
This elevating the conversation about women's health in midlife and
frankly challenging some of the status quote information out there.
Speaker 3 (02:40):
As a medical and cologist, I was really interested in
breast cancer and I was seeing so many young women
with breast cancer and a family history, so trying to
help people not have to face these terrible situations that
they found themselves in was really compelling to me. So
it was really being able to see how devastating this
can be in families and at the same time, how
(03:03):
he doesn't have to be.
Speaker 1 (03:04):
That's doctor Susan Domchuk. She's the executive director of the
Bachsor Center for Braka at the Universe Pennsylvania. She's an
oncologist who specializes in research, treatment, and prevention of BRCA
related cancers. I wanted to have her on the show
to talk about the importance of knowing your family history,
(03:25):
when you should get tested, who should get tested, and
what to do if you, like me, discover you carry
a BRACA mutation. I realize that this can be a
really scary topic for people, but I hope you leave
this conversation like I did, feeling empowered. There are so
many ways we can be proactive about our health, and
(03:47):
simply having more information can make a big impact. So
what do women need to know about their family history?
Is that three generations back? You know? Sometimes when I
(04:07):
take a family history, people will say, Oh, my immediate
family doesn't have any cancer, but I have some aunts
and uncles that may have had cancer. So what do
women need to know about their family history.
Speaker 3 (04:18):
So this is such an important point, is knowing your
family history and knowing this in more detail than previously
has been understood. It's important to know who had cancer
at what ages, going back three generations, as we say,
so looking at cousins and grandparents and more distant relatives
(04:40):
is extremely important. The second thing is that it's not
just breast cancer. For br SA one and ber C two,
those stand for breast cancer one and breast cancer two
because we're just not creative, so BRCA one and BRSA two.
But when we speak about those two specific genes, which
are the most common cause of reditary breast and ovarian cancer,
(05:03):
the cancers that are seen are breast cancer, ovarian cancer,
pancreatic cancer, and prostate cancer. So really having a complete understanding.
In addition, as you're alluding to, people in past generations
didn't necessarily talk about cancer, so finding out why Aunt
Martha died at forty is really important even if the
(05:25):
family didn't talk about it. So having an open conversation
with your relatives about the family history. And by the way,
genetics isn't just about BERC one and two. People die
of colon cancer and they're in colon cancer susceptibility genes,
there's early onset cardiovasclar issues. And finally, individuals who are
Ashkenazi Jewish descent have a much higher chance of having
(05:45):
a BRC one or two mutation. That risk is one
in forty as opposed to one in two hundred in
the general population. So knowing your ethnicity, knowing your family
history are all really important.
Speaker 1 (06:00):
Let's tat a little bit about if a Broka wan
or brock A two gene mutation is being passed down
the father side of the family, it can be a
little bit more challenging to look at, right because your
father is not going to get ovarian cancer. He may
get breast cancer, but it can make it a little
bit more challenging to look at these family histories and
interpret them. Can you just talk about that a little bit.
Speaker 3 (06:21):
In the past, people felt that it was only the
mother's side that mattered, that it was only breast cancer
that mattered when you were thinking about family history and
the risk of having a genetic susceptibility. But none of
that is true. You're really looking at both sides of
the family. Fifty percent of all cancer genetic susceptibility genes.
They will come from the dad, not the mom. If
(06:43):
you line up every r C mutation carry in the world,
half our men. And we can't emphasize this point enough
since it's so often missed. So we can see families
which are really male dominated in which there's a ton
of early on set prostate cancer, and that is justice concerning.
It's also important to recognize that family size matters. So
(07:05):
if it's just your dad and he was an only
child and his father was an only child, cancer susceptibility
genes can be hidden in those types of families. I
want to also emphasize, and this may be a different point,
that we have lower and lower thresholds to do genetic
testing all the time, so sometimes we get a little
caught up in these issues of the exact family history
(07:27):
that we meet for genetic testing. But really it's just
a matter of knowing anything about your family history, including well,
I have a tiny family on my dad's side and
I am concerned about having a genetic susceptibility for whatever reason.
We also recognize that not everybody knows their family history
if they're adopted, or for instance, the Holocaust may have
(07:49):
taken out an entire generation, so we have a much
lower threshold for testing in those situations.
Speaker 1 (07:56):
When we talk about this generic genetic testing for cancer,
what are we talking about in.
Speaker 3 (08:01):
The old days, if you will, you know, fifteen years ago,
we would be testing for two genes, generally BARC one
and br C two. But what we've learned since the
nineties is that there are other genes that are also
associated with breast cancer. One of those is pretty like beer,
say one and two. It's called PALBI two. But there
(08:22):
are some other genes, notably genes called CHECK two and ATM,
which increase your risk of breast cancer only modestly. So
with beer, say one and two, that lifetime risk is
seventy percent, with check two it's about twenty to twenty
five percent. So now when people get genetic testing, they
are almost never tested for just two genes. They're tested
(08:43):
for a panel of genes that will include not only
beer say one and two, but other genes associated with
breast cancer risk. There's colon cancer susceptibility genes as well.
There's kidney cancer susceptibility genes. So in general, we send
sort of a panel of genes that hits the most
common cancers. The specific genes on those panels are looking
(09:07):
for what we call a pathogenic variant otherwise and as
a mutation in a gene that basically makes the protein
not function and that's what increases the risk of cancer.
Speaker 1 (09:19):
And these genes that we're testing for are pretty much
all what we call tumor suppressor genes.
Speaker 3 (09:22):
Correct. That's correct. So what we mean by that is
that all of us are born with two copies of
each gene and in general cancer sceptibility genes. Say, beer
SA one is good. Beer C one actually helps ourselves
repair a specific type of DNA damage called bubble strand
(09:43):
and break. So BERSA one and ber C two are
good for us. They help us. It's only when we
lose them where you are at increased risk or cancer.
Speaker 1 (09:55):
I just want to pause for a moment here and
walk you through this. These concepts can feel so overwhelming
and frankly terrifying for women who are trying to better
understand their family history and their own risk. So you
might have been surprised to hear doctor Domchek say Brako
one and Broko two are good for us. But she's right,
(10:15):
Broca genes aren't cancer causing genes. They're cancer preventing genes.
They're actually helpful. They protect us by fixing damaged DNA.
Like doctor John Chuck said, we're all born with two
copies of those genes. People with Brocca mutations have a
broken copy of the gene. Most of the time, that
one working copy is enough to keep you safe, but
(10:37):
if something happens to damage or turn off that second
working copy, then you don't have any protection. When working properly,
these genes literally suppress tumors. You can imagine. It's almost
like having security guards that keep cancer from getting in.
Only when you lose both guards can cancer develop. Briefly,
(11:00):
what can you tell us about the biology of inherited cancers.
They're a little different. They present a little bit earlier,
so people a little bit younger when they're diagnosed, and
they may have a little bit of a better outcome
to treatment. Correct.
Speaker 3 (11:11):
Yeah, it's a great point, and this is where not
all genetic susceptibility is equal. BRSA one is different than
Chuck two. And the reason I emphasize this is because
when we lump it all together, patients can make decisions
that may not make sense for them. So it's really
important to get gene specific information. BRSA one and two
(11:32):
related cancers generally do occur earlier. The median onset of
the cancers is in the early forties. But you're right
that these tumors for BARSA one and two do seem
to be more sensitive to chemotherapy, and so specifically, an
ovarian cancer outcome is better with ovarian cancer if you
have a br SA one art mutation. In breast cancer,
(11:53):
it's kind of complicated because of the different types of
breast cancer, but in ovarian cancer that prognosis is clearly
better if you have a BRSA one on mutation. So
the reason people with cancer should be tested is because
we have drugs available that we can give them that
will make their cancer do better. Every single person with
(12:15):
ovarian cancer needs to have testing. Every single person with
pancreatic cancer, with metastatic prostate cancer. That's enough. We don't
have to think for a minute about family history. Those
are sufficient for people to get genetic testing for breast cancer. Absolutely,
anyone under fifty and more recently sort of anyone under
(12:36):
sixty five is a candidate for genetic testing, and anyone
with a certain type of breast cancer called triple negative
breast cancer should get genetic testing. We should not leave
a single person in those categories behind. They should all
get genetic testing. At big academic medical centers. We're doing
better and better. We keep track of our metrics, and
(12:58):
we're at over eighty percent in any of those, but
across the country those numbers are terrible. For ovarian cancer,
it's under fifty percent, and it's hard to imagine why
that is, because it actually helps us make decisions about therapy.
So if anyone out there that's listening, if you fall
into any of those groups, or any of your family
(13:18):
members DOE, you absolutely should get genic testing.
Speaker 1 (13:23):
Let's face it, getting a cancer diagnosis is devastating, but
a better understanding of any underlying genetic cause can significantly
improve treatment outcomes coming up. If genetic testing can save lives,
why are we all getting it done? Decoding women's health
(13:44):
will be right back. Welcome back to Decoding women's health.
You might be surprised to learn, as I was, that
even when genetic testing is offered, many people are slow
(14:05):
to take it up. Doctor Susan Donchek has been engaged
in some really important work around this.
Speaker 3 (14:11):
Increasingly, there's discussion about what we call population screening, which
is offering everybody if you will be or s one
and two testing. The complications with that is that it's
not entirely clear how many people really want to do
that right now, and also how we actually will get
it done. We've done some studies to offer genetic testing
(14:36):
to if you will, anyone who's of Ashkenazi Jewish descent.
The uptake wasn't as much as we thought. We did
a study a few years ago testing about four thousand
individuals in that situation, and they didn't have to have
any family history. We thought it would take about three
months to test four thousand people in for cities, and
it took us three years. And other data have really
(14:56):
suggested that it matters if your doctor recommends this to you.
And this is why this is so important to get out.
We need to educate patients people out there in the
community about the potential risk, and we also need to
educate for to have a really low threshold to do
genetic testing if there's a family history or again if
(15:17):
people are of Ashkenazi Jewish to sent we're just going
to the electronic health record and pulling out individuals who've
told their providers that they have a family history and
sending them messages saying you should consider getting genetic testing.
And just in our preliminary data, just that simple effort,
twenty five percent of people schedule appointments to get genetic testing.
(15:39):
So people are interested, they just don't know about it.
I think that we can use simple solutions of asking
people at the right time and then immediately referring them
to genetics. Our primary care doctors have a lot to do,
so this idea that we can expect them to also
do a great screening for these things and get people tested.
(16:01):
It might happen, but it's a lot we need to
help our primary care doctors.
Speaker 1 (16:05):
About what age did you start to consider genetic testing?
Twenty two to twenty five.
Speaker 3 (16:10):
There's really two reasons to test. The first reason is
because you're going to change your medical decision making, and
for most cancer susceptibility genes, you know, we don't start
doing anything different medically until age twenty five. That's when
we start. For instance, restmeris for BERC one mutation cares. Now,
there are sometimes where there's a particularly early onset in
(16:33):
the family where we would potentially do it earlier, but
in general, we have twenty five in our heads. There's
another reason to get genetic testing for BRSA one two
and other cancer sceptibility genes, and that's for reproductive decision making,
and that takes on two different pieces. One pre implantation
genetic testing, So this is when individuals go through in
(16:55):
vitro fertilization, screen the embryos and only reimplant the embryos
that don't have the BRC one or BRC two mutation. Well,
some people are not interested in this, but this technology
is available. So there are times that you know, women
are interested in starting their families before their twenty five
So that's another reason to consider screening. In addition, several
(17:19):
of the genes that we're talking about, and I'll give
br C two as an example. In rare situations, a
baby can inherit two bad copies of ber C two,
one from each parent, and when that occurs, there's a
twenty five percent chance that the baby will have a
condition called fincnianemia, which is a serious medical condition. So
(17:39):
these are all reasons to consider genetic testing sort of
at the time you're starting to think about your family
or medical decision making, and so that matters for the
men too, because in general, we don't really start much
for men in terms of their personal screening until closer
to forty, but when they're ready to start having their children.
If one of their parents has a BERC mutation, then
(18:01):
we certainly talk about screening before they start having their kids.
So I think it's really important that people know that
even if their doctor doesn't bring it up, that it
still may be real to them, and that they can
either talk to their doctors about it they're gynecologists, a
primary care doctor, or see a genetic counselor for testing.
There are also direct to consumer approaches to genetic testing,
(18:23):
where people can just go online and order the tests themselves.
There are pros and cons to those approaches, but right
now you know it's all hands on deck. There are
multiple ways to get this testing done, and we should
make sure that people know about all of them.
Speaker 1 (18:41):
I took the direct to consumer route myself. There are
plenty of companies that offer easy to use at home
testing kits that you can just mail in and get
the results online. The benefit is that it's quick, easy,
and relatively inexpensive. The problem is is that you don't
have guidance and support necessarily that comes with getting tested
(19:01):
with a personal physician. So if you go this route,
I strongly advise connecting with the genetic counselor beforehand. Even
if you think that you're prepared to learn that you
carry a genetic mutation, actually getting that result can still
pack a huge emotional punch. Having an expert in your
corner helps you understand what the result means and what
(19:23):
steps to take next. The National Society of Genetic Counselors
has a registry where you can find professionals to guide you.
Having said that, in an ideal world, everyone would be
guided through genetic testing in person by a physician they trust,
but one of the barriers to this sort of testing
for many patients is cost. In some cases, patients can
(19:46):
get the testing paid for by their insurance. The National
Comprehensive Cancer Network provides guidelines for testing that include the
big factors that we've discussed today, If you're of Ashkenizi
Jewish descent, if you've had blood relatives with a confirmed
cancer causing gene variant, or if you or a family
member has a personal history of a rare or multiple cancers.
(20:08):
I asked doctor Domchek, what about patients are women who
don't fall into these categories.
Speaker 3 (20:13):
If people don't meet those guidelines at most labs, there
are still self pay options that cost about three hundred dollars.
But I will say that navigating this can sometimes be
frustrating and complex for patients. So I think that when
people meet clear criteria for JANK testing, everything goes through
(20:33):
very well. If people are more on the bubble, self
pay options are actually going to be cheaper than if
you will going through insurance where it may not be
covered at.
Speaker 1 (20:42):
All, for people who may not be able to afford
the three hundred dollars. Are you aware of any support
services for these individuals?
Speaker 3 (20:49):
Yes, there are, and oftentimes the labs have held there
are various programs that exist. It does get a little
bit complicated if people do not have insurance at all.
It can be tricky because even if we could get
someone free testing, we're not able to then get them
the medical care that they need. So that is a
(21:10):
big gap right now. Is people who are completely uninsured.
We really do struggle because even if we could test them,
we would not really be able to care for them,
and that doesn't feel great. So hopefully all insurance problems
in the United States will be fixed and we won't
have to worry about it. But I'm not going to
hold my breath right now for that.
Speaker 1 (21:30):
So a lot of upside to genetic testing allowing you
to do some planning, and we'll move into that in
just a moment.
Speaker 3 (21:36):
Any downsides, Sure, this is information that can be extremely
difficult to learn. I had a physician once tell me
she felt that the genetic testing both saved your life
had ruined it. And she didn't really mean ruin it,
but she just at dealing with this information making the
decisions she had to make well really difficult. And so,
(21:58):
first of all, we always like to emphasize that when
you get your genetic test result back, if it's positive,
that was always there. You were positive from the time
you were born. You know, you didn't change on a
dime day to day. We also like to talk about
lifetime risks. So when we talk about lifetime risk of
cancer as highly seventy percent, that's not your risk tomorrow,
that's your risk over your whole life. But you can
(22:20):
imagine that feeling getting that information is really overwhelming, and
so our job is to try to counsel people through it.
To focus on the immediate next steps of what needs
to happen. Currently, the only effective strategy for a varying
cancer risk reduction is early surgery, so premenopausal to me
(22:40):
removable of your ovaries before you or otherwise we go
into menopause, and that has significant issues for women. We
try to get people through it as best we can,
but it's still fun to have to consider these things
and then deciding whether to continue to screen or do astectomy.
That can be challenging for parents to get tested. We
(23:01):
see a lot that when individuals get tested that have children,
they can feel very sad and sometimes guilty about the
potential that they've passed this belong to their children. Of course,
we all pass along good and bad genes to our kids.
In this case, you just kind of know what it is.
But these are real issues that we know that people
struggle with, and our job is to try to help
(23:22):
people through this time and really focus on the fact
that this information can be life saving, but at the
same time acknowledge the grief that's involved in having to
make these decisions.
Speaker 1 (23:33):
So I'm diagnosed with the bracket one mutation in twenty
twenty five, what does taking action look like as a
younger woman, as a primin apausal woman.
Speaker 3 (23:42):
Yes, and so in twenty twenty five, there are clear
things that women can do, but we are actively hoping
for better options. So right now, at twenty five, all
someone needs to do is get a breast MRI once
a year. The risk of developing breast cancer prior to
age thirty when you're a twenty five year old beer
C one mutation carries less than five percent, but that's
(24:05):
still much higher than an average woman. So brust emri
once a year. At thirty, we have to mammogram, so
that every six months you're getting an MRI or a mammogram. Unfortunately,
between age thirty five and forty women should undergo remove
all the pilopian tubes and ovaries. So this is for
bars one now. Risk reducing mass tec to me or
(24:27):
prophylactic masks tec to me can be done at any
time with an individual with a br c in one
or two or other gene mutations. Some women are not
interested in mask tec tomy at all and will continue screening,
so we like to have an honest conversation about their
goals about body image, about sexuality, and other quality of
life issues as people make their decisions.
Speaker 1 (24:50):
What about just removal of the pelopian tubes alone, without
removing the ovaries. Is that data mature enough for us
to make that recommendation now?
Speaker 3 (24:57):
Not? Yeah, but boy, I want it to be.
Speaker 1 (24:59):
So.
Speaker 3 (25:00):
The theory behind this, as you're alluding to, is that
there's data that many ovarian cancers arise in the philopian
tube and that potentially if we just remove the philippian tubes,
we can decrease the risk of ovarian cancer. And there's
some interesting sort of data out there, including a study
that's being done in British Columbia where every woman who's
(25:21):
coming in to have her tubes tied just has their
tubes removed, and again the very early data suggests that
there's a decrease in ovarian cancer risk. We call that
an opportunistic salve in theectimy. So that I think nobody
should have their tubes tied anymore, you know, in the
general population or beer sacres, they should have their tubes
removed if they're using that for their family planning and
(25:44):
first control. The question becomes in beer sacres, how certain
are we about this? Because again, ovarian cancer has no
effective screening and Most women who are diagnosed with ovarian
cancer are diagnosed at elite stage, and most women with
a late stage ovarian cancer die of their disease. So
this is where the challenge is. The studies are ongoing,
but when will we feel strong enough to recommend that
(26:06):
as a routine care when we know how bad ovarian
cancer is. Right now, again, we don't have data sufficient
to tell people that they can avoid having their ovaries removed.
So what we're seeing more and more of is that
a b r C one Karen might have her twos
removed at thirty five and then her ovaries removed at forty.
For a br C two care, that's more like forty
(26:27):
and forty five.
Speaker 1 (26:28):
When do you think that data is going to be
mature five years, ten years, twenty years.
Speaker 3 (26:32):
Here's my worry that if people are getting their twos
removed at thirty five and then they still get their
ovaries removed at forty one, we won't have the data.
People have to keep their ovaries in long enough for
us to prove it works right sort of past forty
five or even un till each fifty. And I think
this is the tension I always have in the clinic
(26:54):
I'm really a clinician. First, I'm taking care of my patients.
I'm a bit of a researcher. Second, for my patients,
I don't want her to keep her overrays in. But
from a research perspective, and less enough people continue to
keep their ovaries, we're not going to have the data.
So I think it's going to be a little bit tricky,
and it might be a little bit entirely.
Speaker 1 (27:15):
Once I found out that I was a Brocco one carrier,
the decision to remove my uterus, ovaries and fallopian tubes
for me was straightforward. I was older, I'd already had
children and experienced menopause. For younger women, making the same
choice means two things. First, no further chance to conceive,
(27:36):
and second, entering menopause overnight. These are big decisions and
surgery might not be the best course of action for everyone.
When we come back from the break, we'll discuss other
preventive strategies for women to lower their risk, and we'll
talk about some groundbreaking new treatments on the horizon. More
from my conversation with Darja Susan Domchek in just a moment.
(28:11):
Welcome back to the show. I'm speaking with doctor Susan
damchek All about genetic testing. Her work is at the
forefront of cancer prevention, cutting edge strategies that seek to
stop cancer in its earliest stages. But before we get
to that, I wanted to ask doctor Domck about some
newer methods for identifying genetic risk. Let's move into just
(28:33):
the different types of genetic testing that are out there
now in terms of polygenic risk scores and whole genome sequencing.
Can you speak to these newer forms of genetic testing
a little bit?
Speaker 3 (28:42):
Sure, So let's start with polygenic risk scores. And but
that is a single alteration in FUERCA one increases your
risk of breast cancer by up to seventy percent. It
increases your risk google veering cancer up to forty five percent.
Polygenic risk scores look at small, little changes throughout your DNA.
(29:03):
The challenges of polygenic risk scores are that they're very
dependent on ethnicity, and so in the United States when
people are often sort of ethnically diverse, we haven't really
figured it all out yet. Okay, So moving on a
whole genome. So what is that? So, just as a reminder,
we have a certain number of genes over twenty thousand.
(29:26):
But when we test for genetics astibility, what we usually
do is focus on genes known to be associated with cancer.
So that can be a twenty five gene panel or
an eighty gene panel or something like that. There is
an approach that you can take called whole xome sequencing,
which just sequences the known genes, but it sequences all
the nome genes. And then there's whole genome sequencing, which
(29:50):
sequences the whole genome. If you do a whole xome sequencing,
you will find stuff. Most of us have stuff. The
question then becomes does that stuff matter? And it might
seem obvious that that stuff should matter, right that if
you find something that it obviously should matter. But it
turns out that genetics is not that simple as we
(30:13):
sometimes say. Genetics is not destiny. Just because you have
an alteration in some finding doesn't mean that you're going
to get that condition. And there are a lot of
genes where the risks associated with those genetic mutations aren't
very high. An example I'll give is something called SDHA
alterations in that gene predispose you to certain types of
(30:34):
rare tumors, but the risk of that happening if you
have an SDHA mutation is less than five percent. So
if we identify someone with that, generally speaking, we don't
do anything about it unless there's a family history consistent
with it. I'm only using that as an example to
show how you can get into trouble with things like
collexm and whole genome sequencing, which is we're going to
(30:57):
find a lot of stuff, but we won't necessarily know
exactly how to use it for that individual patient.
Speaker 1 (31:03):
Let's move into prevention strategies, right for the woman who's
not ready for prophylactic surgery, undergoing some screening, birth control pills,
even life style. What are the impact of these strategies
for women who carry brocka wan and Brocketo mutation.
Speaker 3 (31:15):
I think lifestyle is you know, the effects in berca
in one and two mutation carriers may be modest, just
because the genetics stuff is driving a lot of the risk.
Having said that, healthy weight, minimizing alcohol, regular exercise, not smoking,
these are all excellent things to do for women. There's
a lot of debate about what safe level of alcohol is,
(31:36):
but there has been some suggestion that you know, up
to three drinks a week. The risk is very very low,
so that's lifestyle always a good thing to do. The
data for medications such as tamoxifin, loxifen, and another drug
called exemesting in terms of decreasing the risk of breast
cancer is limited in beer CA carriers, although it does
seem like there is an impact in terms of ovarian
(31:58):
cancer risk reduction. Oral contraceptive pills do seem to decrease
the risk of a virile cancer. They also do slightly
increase the risk of breast cancer, so it's a risk
benefit decision. People have endometriosis or terrible heavy bleeding or
just really terrible cycles in general, and birth control pills
are really helpful or they need birth control, and particularly
(32:21):
in this day and age in the United States, it's
really important that people have access to affective birth control.
So the birth control discussion with the risk benefit profile
just needs to be individualized, so no easy answers there.
We're obviously really interested in other approaches, so this new
era of getting people better options is super important.
Speaker 1 (32:42):
Screening strategies, so breast screening is pretty well established with
MRI mammogram ultrasound ovarian cancer screening a mind filled anything
that you're excited about.
Speaker 3 (32:53):
Oh, varian cancer screening, it's just so difficult. As you know,
we've been through other blood tests in the distant past, overshore,
overseek over one, and I don't even remember all the
OVAs that came and went over the years that weren't
good tests. You know, I think that these new multi
cancer early detection tests are interesting but as yet unproven
and ovarying cancer early detection. This is why, unfortunately everyone
(33:18):
feels so strongly still about removal of the oversease. It's
because we don't have this well established the issue of
transnagal ultrasend. They really just don't work very well at all,
and there's a lot of false positives associated with them
because pre menopausal women have all sorts of cysts depending
on the timing of their cycle. So you know, the
(33:39):
guidelines have sort of been all over the map given
the absence of data. But a common strategy is to
start ovarian cancer screening sort of at the time you
would start considering removal of the ovarias, so like thirty
five for BARC one or forty for br C two,
in which case a false positive that led you down
to removal of the ovarias. I'm not saying is not
(34:00):
so bad because it's we're still taling with the impact,
but it's in the range that we would consider that.
So I'm curious about your approach to it, but that's
often the approach that we take in the absence of
better data.
Speaker 1 (34:11):
I'm looking forward to research and development of new screening tools.
I think that you know twenty five ultracent. We use them,
employ them, but realize that they're limited. But as the
best we can do. Have to be super careful though
in terms of caution, interpretation of results, really really really careful.
But I want to get into your really exciting work
(34:32):
with cancer interception and cancer vaccines. You know, our family
history is pancreas cancer. You can't take out you're pancreas,
and screening for pancreas cancer is limited and not well proven.
So talk to me about cancer interception and cancer prevention vaccines.
Speaker 3 (34:47):
Yeah. Sure, So this phrase cancer interception, what does it
even mean anyway, It's a way to try to differentiate
from prevention. You know, when we talk about prevention, if
it's a little bit like you don't smoke because smoking
causes those changes that lead to cancer. Right, So prevention
is you don't smoke, so you don't even start those changes.
Cancer interception, which was going by Loose Blackburn and no
(35:11):
prize winning scientists. It's trying to target the earliest stages
of cancer development. The cancer has just started, but you
can't detect it yet, and so that's cancer interception. So
the idea here is that we try to target those
first cells that are turning into cancer in a beer
C carrier, so maybe I've lost the second copy of
beer C for instance. So when you think about potential strategies,
(35:35):
one of those strategies could be immune interception. So we
really have a better understanding over the last you know,
fifteen plus years that the immune system is incredibly important
in cancer in a way that would have been you know,
laughed at twenty five years ago. But we know that
we can use immune therapies to help treat cancer. So
(35:56):
one of the strategies that we're trying is to develop
a vaccine that might develop immune cells that find those
earliest cancer cells. You know, they're surveying your body and
then as soon as that cell develops, they they target
it and kill it. So we recently completed a study
where we did vaccinate healthy BRC carriers using something called
(36:17):
the DNA plasmid vaccine. What we were vaccine two isn't
specific to BRC carriers, but it's the idea that you
could identify a group that's at a high enough risk
to try this. So the vaccine was safe, and now
we're waiting to get the imminology results and then figure
out our next phase. So that's sort of one approach.
Let's use the immune system, let's target different types of
(36:41):
immune strategies. We are also looking at mRNA types of
approaches to vaccines. I mean, I do not view vaccines
as a dirty word here, but if you want to
call it immune interception as opposed to vaccines, I'll take
that as well. But there's other ways to think about interceptions.
So let's talk about pancreatic cancer. Pancreatic cancer. The risk
(37:01):
of pancreatic cancer's highest in br C two rather than
BRC one mutation carres, although the risk is elevated in both,
and as you said, pancreatic cancer is a tough cancer.
We do offer screening with either a endoscopic ulture sound
or abdominal MRI, but as you mentioned, you know, it
is limited, but almost all pancreatic cancers develop something called
k Wrass mutations. So we actually also have work being
(37:25):
done in the pass Or center looking at whether or
not k wrass inhibitors in mice can decrease the risk
of developing pancreatic cancer. So those are some some of
the ideas that we have. There's other work going on.
Could we use short doses of apartment hit er, these
drugs that we use in the advanced cancer setting and
in high risk breast cancer setting, could we use those
(37:47):
intermittently to if you will, weed the garden and take
out all those weeds before they develop into something, right,
intermittently getting rid of all of those pre cancerous cells.
So more to come, but it's a really exciting area
that we're working on.
Speaker 1 (38:03):
If listeners could take away one point from this conversation,
what would you like it to be to.
Speaker 3 (38:09):
Be proactive about getting your family history taken seriously? I
think that patients can be, if you will, a little
put off and be like, oh, don't worry about that.
That's not enough to get genetic testing. And the fact
is is that most doctors out there learned about genetic
testing in medical school, you know, fifteen or twenty years ago,
(38:30):
and they're not entirely up to date. It's not their fault.
There's too much to do. But there's a lot of
resources out there, and you can self refer to a
genetic counselor to get more information if you're not getting
the answers that you want.
Speaker 1 (38:43):
Are there resources for our listeners actually in terms of
where they can go to learn more about this.
Speaker 3 (38:49):
Yeah, we do at faster dot org so BA s
ser dot org. We have a lot about why genetic
testing can be helpful and have provided some resources, including
any large comprehensive cancer center will have genetic counselors available.
There are plenty of physicians, gecologists, and primary care directors
(39:10):
who comfortable with this and do you do it? So
asking your primary care doctor first can always make sense,
But if your primary care doctor doesn't know a lot
about it or it's not really offering it to you,
don't stop there. There are lots of different ways to
get this done.
Speaker 1 (39:29):
I had cancer and I had seen some of the
best physicians in the country for treatment. None of them
ever mentioned to me genetic testing. I am literally a geneticist,
and I didn't think that this applied to me. If
you have family members with breast ovarian, pancreatic, or prostate cancer,
it's worth it to consider genetic testing, even if your
(39:51):
doctor hasn't suggested it, Even if you've been tested in
the past a ten years or so, I'd recommend thinking
about testing again. Technology is getting better and better each day.
We're aware of more cancer causing genes than we were
a decade ago, and we have more tools to treat
those specific diseases. Your health insurance may cover genetic testing
(40:12):
if you fall into a high risk group, but if not,
there are lots of alternative ways that you can get
genetic information you need. Direct to consumer options like I
did are quick and easy, but I would always recommend
connecting with a genetic counselor to help interpret your results.
If you are positive for genetic mutation, there are a
multitude of preventative measures that you can take, from prophylactic
(40:35):
surgeries to risk reducing drugs like tomoxifen or reluxaphene. Ultimately,
you are responsible for your own health. You have to
advocate for yourself, but you don't have to do it alone.
There are amazing places like the beast Or Center that
can help you navigate this, Organizations that have testing, genetic counseling,
(40:56):
treatment options, and positive communities all in one place. Taking
that first step could save your life or the life
of someone you love. Coming up on the next episode
of Decoding Women's Health, I speak with a world renowned
(41:16):
expert in medical cannabis. You are not going to want
to miss this one.
Speaker 4 (41:21):
The top three indications for medical cannabis use across the
country are chronic pain, mood or anxiety, and sleep disruption.
Not surprisingly, these are the three top conditions we hear
about in individuals who are either perimenopausal or postmenopausal.
Speaker 1 (41:35):
Decoding Women's Health is a production of Pushkin Industries and
the Atria Health and Research Institute. This episode was produced
by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid,
mastering by Sarah Buguer. Our associate producer is Sonia Gerwit,
backchecking by doctor David Dodick. Our executive producer is Alexandra Garreton.
(41:57):
Our theme song was composed by HANNS. Brown. Concept and
creative development by Shavn O'Connor. A special thanks to Alan
Tish David Saltzman, Sarah Nix, Eric Sandler, More Ratner, Amy Hagdorn,
Owen Miller, Jordan McMillan, and Greta Cohne. If you have
(42:18):
questions about women's health and midlife and want expert advice,
leave us a voicemail at four FI five two oh one,
three three eight five, or send us a message at
Decoding Women's Health at pushkin dot FM. I'm doctor Elizabeth Pointer,
and thanks for listening. Until next time,
Pushkin.
Speaker 2 (00:24):
This show is not a substitute for professional medical advice, diagnosis,
or treatment. It is for informational purposes. Please consult your
healthcare professional with any medical questions.
Speaker 1 (00:37):
My mom was diagnosed with breast cancer in her fifties. Luckily,
it wasn't complicated and she quickly went into remission. But
this April, she was diagnosed with pancreatic cancer, one of
the most lethal and hardest cancers to treat. It was
devastating news. I assumed it wasn't a hereditary cancer. Most aren't,
but some cancers can be caused by genetic mutations like
(01:01):
the Brca one and Brca two genes, sometimes referred to
as the Braca genes. These are genes that normally protect
cells from damage, but when they don't work, cancerous skyrockets.
Years ago, I was actually testing myself for Brocca mutations.
I sent off blood work for genetic testing with a
private company. I never got the results back, and I
(01:23):
sort of forgot about it. That is until my mom's
doctors tested her blood and found out that she carried
a Broco one mutation. Her cancer had a genetic heritable element.
I contacted the testing company that I had sent my
blood work to years earlier, and I finally got those results.
(01:44):
I was positive for a BRCA one mutation. Myself, I
would have been livid. If I wasn't so scared. I'd
already had my own battle with HPV related cancer in
twenty twenty one, and as a pelvic surgeon, I know
too well the realities of ovarian cancer. Within weeks, I
had my ovaries and fallopian tubes removed. The wildest part.
(02:07):
I have a PhD in genetics. I worked with some
of the best vision icians and scientists in the world.
I am an expert in ovarian cancer, yet this potentially
fatal mutation when undetected in me for nearly sixty three years.
I'm doctor Elizabeth Pointer. And this is Decoding Women's Health,
(02:27):
a show from Pushkin Industries and the Atria Health Institute.
This elevating the conversation about women's health in midlife and
frankly challenging some of the status quote information out there.
Speaker 3 (02:40):
As a medical and cologist, I was really interested in
breast cancer and I was seeing so many young women
with breast cancer and a family history, so trying to
help people not have to face these terrible situations that
they found themselves in was really compelling to me. So
it was really being able to see how devastating this
can be in families and at the same time, how
(03:03):
he doesn't have to be.
Speaker 1 (03:04):
That's doctor Susan Domchuk. She's the executive director of the
Bachsor Center for Braka at the Universe Pennsylvania. She's an
oncologist who specializes in research, treatment, and prevention of BRCA
related cancers. I wanted to have her on the show
to talk about the importance of knowing your family history,
(03:25):
when you should get tested, who should get tested, and
what to do if you, like me, discover you carry
a BRACA mutation. I realize that this can be a
really scary topic for people, but I hope you leave
this conversation like I did, feeling empowered. There are so
many ways we can be proactive about our health, and
(03:47):
simply having more information can make a big impact. So
what do women need to know about their family history?
Is that three generations back? You know? Sometimes when I
(04:07):
take a family history, people will say, Oh, my immediate
family doesn't have any cancer, but I have some aunts
and uncles that may have had cancer. So what do
women need to know about their family history.
Speaker 3 (04:18):
So this is such an important point, is knowing your
family history and knowing this in more detail than previously
has been understood. It's important to know who had cancer
at what ages, going back three generations, as we say,
so looking at cousins and grandparents and more distant relatives
(04:40):
is extremely important. The second thing is that it's not
just breast cancer. For br SA one and ber C two,
those stand for breast cancer one and breast cancer two
because we're just not creative, so BRCA one and BRSA two.
But when we speak about those two specific genes, which
are the most common cause of reditary breast and ovarian cancer,
(05:03):
the cancers that are seen are breast cancer, ovarian cancer,
pancreatic cancer, and prostate cancer. So really having a complete understanding.
In addition, as you're alluding to, people in past generations
didn't necessarily talk about cancer, so finding out why Aunt
Martha died at forty is really important even if the
(05:25):
family didn't talk about it. So having an open conversation
with your relatives about the family history. And by the way,
genetics isn't just about BERC one and two. People die
of colon cancer and they're in colon cancer susceptibility genes,
there's early onset cardiovasclar issues. And finally, individuals who are
Ashkenazi Jewish descent have a much higher chance of having
(05:45):
a BRC one or two mutation. That risk is one
in forty as opposed to one in two hundred in
the general population. So knowing your ethnicity, knowing your family
history are all really important.
Speaker 1 (06:00):
Let's tat a little bit about if a Broka wan
or brock A two gene mutation is being passed down
the father side of the family, it can be a
little bit more challenging to look at, right because your
father is not going to get ovarian cancer. He may
get breast cancer, but it can make it a little
bit more challenging to look at these family histories and
interpret them. Can you just talk about that a little bit.
Speaker 3 (06:21):
In the past, people felt that it was only the
mother's side that mattered, that it was only breast cancer
that mattered when you were thinking about family history and
the risk of having a genetic susceptibility. But none of
that is true. You're really looking at both sides of
the family. Fifty percent of all cancer genetic susceptibility genes.
They will come from the dad, not the mom. If
(06:43):
you line up every r C mutation carry in the world,
half our men. And we can't emphasize this point enough
since it's so often missed. So we can see families
which are really male dominated in which there's a ton
of early on set prostate cancer, and that is justice concerning.
It's also important to recognize that family size matters. So
(07:05):
if it's just your dad and he was an only
child and his father was an only child, cancer susceptibility
genes can be hidden in those types of families. I
want to also emphasize, and this may be a different point,
that we have lower and lower thresholds to do genetic
testing all the time, so sometimes we get a little
caught up in these issues of the exact family history
(07:27):
that we meet for genetic testing. But really it's just
a matter of knowing anything about your family history, including well,
I have a tiny family on my dad's side and
I am concerned about having a genetic susceptibility for whatever reason.
We also recognize that not everybody knows their family history
if they're adopted, or for instance, the Holocaust may have
(07:49):
taken out an entire generation, so we have a much
lower threshold for testing in those situations.
Speaker 1 (07:56):
When we talk about this generic genetic testing for cancer,
what are we talking about in.
Speaker 3 (08:01):
The old days, if you will, you know, fifteen years ago,
we would be testing for two genes, generally BARC one
and br C two. But what we've learned since the
nineties is that there are other genes that are also
associated with breast cancer. One of those is pretty like beer,
say one and two. It's called PALBI two. But there
(08:22):
are some other genes, notably genes called CHECK two and ATM,
which increase your risk of breast cancer only modestly. So
with beer, say one and two, that lifetime risk is
seventy percent, with check two it's about twenty to twenty
five percent. So now when people get genetic testing, they
are almost never tested for just two genes. They're tested
(08:43):
for a panel of genes that will include not only
beer say one and two, but other genes associated with
breast cancer risk. There's colon cancer susceptibility genes as well.
There's kidney cancer susceptibility genes. So in general, we send
sort of a panel of genes that hits the most
common cancers. The specific genes on those panels are looking
(09:07):
for what we call a pathogenic variant otherwise and as
a mutation in a gene that basically makes the protein
not function and that's what increases the risk of cancer.
Speaker 1 (09:19):
And these genes that we're testing for are pretty much
all what we call tumor suppressor genes.
Speaker 3 (09:22):
Correct. That's correct. So what we mean by that is
that all of us are born with two copies of
each gene and in general cancer sceptibility genes. Say, beer
SA one is good. Beer C one actually helps ourselves
repair a specific type of DNA damage called bubble strand
(09:43):
and break. So BERSA one and ber C two are
good for us. They help us. It's only when we
lose them where you are at increased risk or cancer.
Speaker 1 (09:55):
I just want to pause for a moment here and
walk you through this. These concepts can feel so overwhelming
and frankly terrifying for women who are trying to better
understand their family history and their own risk. So you
might have been surprised to hear doctor Domchek say Brako
one and Broko two are good for us. But she's right,
(10:15):
Broca genes aren't cancer causing genes. They're cancer preventing genes.
They're actually helpful. They protect us by fixing damaged DNA.
Like doctor John Chuck said, we're all born with two
copies of those genes. People with Brocca mutations have a
broken copy of the gene. Most of the time, that
one working copy is enough to keep you safe, but
(10:37):
if something happens to damage or turn off that second
working copy, then you don't have any protection. When working properly,
these genes literally suppress tumors. You can imagine. It's almost
like having security guards that keep cancer from getting in.
Only when you lose both guards can cancer develop. Briefly,
(11:00):
what can you tell us about the biology of inherited cancers.
They're a little different. They present a little bit earlier,
so people a little bit younger when they're diagnosed, and
they may have a little bit of a better outcome
to treatment. Correct.
Speaker 3 (11:11):
Yeah, it's a great point, and this is where not
all genetic susceptibility is equal. BRSA one is different than
Chuck two. And the reason I emphasize this is because
when we lump it all together, patients can make decisions
that may not make sense for them. So it's really
important to get gene specific information. BRSA one and two
(11:32):
related cancers generally do occur earlier. The median onset of
the cancers is in the early forties. But you're right
that these tumors for BARSA one and two do seem
to be more sensitive to chemotherapy, and so specifically, an
ovarian cancer outcome is better with ovarian cancer if you
have a br SA one art mutation. In breast cancer,
(11:53):
it's kind of complicated because of the different types of
breast cancer, but in ovarian cancer that prognosis is clearly
better if you have a BRSA one on mutation. So
the reason people with cancer should be tested is because
we have drugs available that we can give them that
will make their cancer do better. Every single person with
(12:15):
ovarian cancer needs to have testing. Every single person with
pancreatic cancer, with metastatic prostate cancer. That's enough. We don't
have to think for a minute about family history. Those
are sufficient for people to get genetic testing for breast cancer. Absolutely,
anyone under fifty and more recently sort of anyone under
(12:36):
sixty five is a candidate for genetic testing, and anyone
with a certain type of breast cancer called triple negative
breast cancer should get genetic testing. We should not leave
a single person in those categories behind. They should all
get genetic testing. At big academic medical centers. We're doing
better and better. We keep track of our metrics, and
(12:58):
we're at over eighty percent in any of those, but
across the country those numbers are terrible. For ovarian cancer,
it's under fifty percent, and it's hard to imagine why
that is, because it actually helps us make decisions about therapy.
So if anyone out there that's listening, if you fall
into any of those groups, or any of your family
(13:18):
members DOE, you absolutely should get genic testing.
Speaker 1 (13:23):
Let's face it, getting a cancer diagnosis is devastating, but
a better understanding of any underlying genetic cause can significantly
improve treatment outcomes coming up. If genetic testing can save lives,
why are we all getting it done? Decoding women's health
(13:44):
will be right back. Welcome back to Decoding women's health.
You might be surprised to learn, as I was, that
even when genetic testing is offered, many people are slow
(14:05):
to take it up. Doctor Susan Donchek has been engaged
in some really important work around this.
Speaker 3 (14:11):
Increasingly, there's discussion about what we call population screening, which
is offering everybody if you will be or s one
and two testing. The complications with that is that it's
not entirely clear how many people really want to do
that right now, and also how we actually will get
it done. We've done some studies to offer genetic testing
(14:36):
to if you will, anyone who's of Ashkenazi Jewish descent.
The uptake wasn't as much as we thought. We did
a study a few years ago testing about four thousand
individuals in that situation, and they didn't have to have
any family history. We thought it would take about three
months to test four thousand people in for cities, and
it took us three years. And other data have really
(14:56):
suggested that it matters if your doctor recommends this to you.
And this is why this is so important to get out.
We need to educate patients people out there in the
community about the potential risk, and we also need to
educate for to have a really low threshold to do
genetic testing if there's a family history or again if
(15:17):
people are of Ashkenazi Jewish to sent we're just going
to the electronic health record and pulling out individuals who've
told their providers that they have a family history and
sending them messages saying you should consider getting genetic testing.
And just in our preliminary data, just that simple effort,
twenty five percent of people schedule appointments to get genetic testing.
(15:39):
So people are interested, they just don't know about it.
I think that we can use simple solutions of asking
people at the right time and then immediately referring them
to genetics. Our primary care doctors have a lot to do,
so this idea that we can expect them to also
do a great screening for these things and get people tested.
(16:01):
It might happen, but it's a lot we need to
help our primary care doctors.
Speaker 1 (16:05):
About what age did you start to consider genetic testing?
Twenty two to twenty five.
Speaker 3 (16:10):
There's really two reasons to test. The first reason is
because you're going to change your medical decision making, and
for most cancer susceptibility genes, you know, we don't start
doing anything different medically until age twenty five. That's when
we start. For instance, restmeris for BERC one mutation cares. Now,
there are sometimes where there's a particularly early onset in
(16:33):
the family where we would potentially do it earlier, but
in general, we have twenty five in our heads. There's
another reason to get genetic testing for BRSA one two
and other cancer sceptibility genes, and that's for reproductive decision making,
and that takes on two different pieces. One pre implantation
genetic testing, So this is when individuals go through in
(16:55):
vitro fertilization, screen the embryos and only reimplant the embryos
that don't have the BRC one or BRC two mutation. Well,
some people are not interested in this, but this technology
is available. So there are times that you know, women
are interested in starting their families before their twenty five
So that's another reason to consider screening. In addition, several
(17:19):
of the genes that we're talking about, and I'll give
br C two as an example. In rare situations, a
baby can inherit two bad copies of ber C two,
one from each parent, and when that occurs, there's a
twenty five percent chance that the baby will have a
condition called fincnianemia, which is a serious medical condition. So
(17:39):
these are all reasons to consider genetic testing sort of
at the time you're starting to think about your family
or medical decision making, and so that matters for the
men too, because in general, we don't really start much
for men in terms of their personal screening until closer
to forty, but when they're ready to start having their children.
If one of their parents has a BERC mutation, then
(18:01):
we certainly talk about screening before they start having their kids.
So I think it's really important that people know that
even if their doctor doesn't bring it up, that it
still may be real to them, and that they can
either talk to their doctors about it they're gynecologists, a
primary care doctor, or see a genetic counselor for testing.
There are also direct to consumer approaches to genetic testing,
(18:23):
where people can just go online and order the tests themselves.
There are pros and cons to those approaches, but right
now you know it's all hands on deck. There are
multiple ways to get this testing done, and we should
make sure that people know about all of them.
Speaker 1 (18:41):
I took the direct to consumer route myself. There are
plenty of companies that offer easy to use at home
testing kits that you can just mail in and get
the results online. The benefit is that it's quick, easy,
and relatively inexpensive. The problem is is that you don't
have guidance and support necessarily that comes with getting tested
(19:01):
with a personal physician. So if you go this route,
I strongly advise connecting with the genetic counselor beforehand. Even
if you think that you're prepared to learn that you
carry a genetic mutation, actually getting that result can still
pack a huge emotional punch. Having an expert in your
corner helps you understand what the result means and what
(19:23):
steps to take next. The National Society of Genetic Counselors
has a registry where you can find professionals to guide you.
Having said that, in an ideal world, everyone would be
guided through genetic testing in person by a physician they trust,
but one of the barriers to this sort of testing
for many patients is cost. In some cases, patients can
(19:46):
get the testing paid for by their insurance. The National
Comprehensive Cancer Network provides guidelines for testing that include the
big factors that we've discussed today, If you're of Ashkenizi
Jewish descent, if you've had blood relatives with a confirmed
cancer causing gene variant, or if you or a family
member has a personal history of a rare or multiple cancers.
(20:08):
I asked doctor Domchek, what about patients are women who
don't fall into these categories.
Speaker 3 (20:13):
If people don't meet those guidelines at most labs, there
are still self pay options that cost about three hundred dollars.
But I will say that navigating this can sometimes be
frustrating and complex for patients. So I think that when
people meet clear criteria for JANK testing, everything goes through
(20:33):
very well. If people are more on the bubble, self
pay options are actually going to be cheaper than if
you will going through insurance where it may not be
covered at.
Speaker 1 (20:42):
All, for people who may not be able to afford
the three hundred dollars. Are you aware of any support
services for these individuals?
Speaker 3 (20:49):
Yes, there are, and oftentimes the labs have held there
are various programs that exist. It does get a little
bit complicated if people do not have insurance at all.
It can be tricky because even if we could get
someone free testing, we're not able to then get them
the medical care that they need. So that is a
(21:10):
big gap right now. Is people who are completely uninsured.
We really do struggle because even if we could test them,
we would not really be able to care for them,
and that doesn't feel great. So hopefully all insurance problems
in the United States will be fixed and we won't
have to worry about it. But I'm not going to
hold my breath right now for that.
Speaker 1 (21:30):
So a lot of upside to genetic testing allowing you
to do some planning, and we'll move into that in
just a moment.
Speaker 3 (21:36):
Any downsides, Sure, this is information that can be extremely
difficult to learn. I had a physician once tell me
she felt that the genetic testing both saved your life
had ruined it. And she didn't really mean ruin it,
but she just at dealing with this information making the
decisions she had to make well really difficult. And so,
(21:58):
first of all, we always like to emphasize that when
you get your genetic test result back, if it's positive,
that was always there. You were positive from the time
you were born. You know, you didn't change on a
dime day to day. We also like to talk about
lifetime risks. So when we talk about lifetime risk of
cancer as highly seventy percent, that's not your risk tomorrow,
that's your risk over your whole life. But you can
(22:20):
imagine that feeling getting that information is really overwhelming, and
so our job is to try to counsel people through it.
To focus on the immediate next steps of what needs
to happen. Currently, the only effective strategy for a varying
cancer risk reduction is early surgery, so premenopausal to me
(22:40):
removable of your ovaries before you or otherwise we go
into menopause, and that has significant issues for women. We
try to get people through it as best we can,
but it's still fun to have to consider these things
and then deciding whether to continue to screen or do astectomy.
That can be challenging for parents to get tested. We
(23:01):
see a lot that when individuals get tested that have children,
they can feel very sad and sometimes guilty about the
potential that they've passed this belong to their children. Of course,
we all pass along good and bad genes to our kids.
In this case, you just kind of know what it is.
But these are real issues that we know that people
struggle with, and our job is to try to help
(23:22):
people through this time and really focus on the fact
that this information can be life saving, but at the
same time acknowledge the grief that's involved in having to
make these decisions.
Speaker 1 (23:33):
So I'm diagnosed with the bracket one mutation in twenty
twenty five, what does taking action look like as a
younger woman, as a primin apausal woman.
Speaker 3 (23:42):
Yes, and so in twenty twenty five, there are clear
things that women can do, but we are actively hoping
for better options. So right now, at twenty five, all
someone needs to do is get a breast MRI once
a year. The risk of developing breast cancer prior to
age thirty when you're a twenty five year old beer
C one mutation carries less than five percent, but that's
(24:05):
still much higher than an average woman. So brust emri
once a year. At thirty, we have to mammogram, so
that every six months you're getting an MRI or a mammogram. Unfortunately,
between age thirty five and forty women should undergo remove
all the pilopian tubes and ovaries. So this is for
bars one now. Risk reducing mass tec to me or
(24:27):
prophylactic masks tec to me can be done at any
time with an individual with a br c in one
or two or other gene mutations. Some women are not
interested in mask tec tomy at all and will continue screening,
so we like to have an honest conversation about their
goals about body image, about sexuality, and other quality of
life issues as people make their decisions.
Speaker 1 (24:50):
What about just removal of the pelopian tubes alone, without
removing the ovaries. Is that data mature enough for us
to make that recommendation now?
Speaker 3 (24:57):
Not? Yeah, but boy, I want it to be.
Speaker 1 (24:59):
So.
Speaker 3 (25:00):
The theory behind this, as you're alluding to, is that
there's data that many ovarian cancers arise in the philopian
tube and that potentially if we just remove the philippian tubes,
we can decrease the risk of ovarian cancer. And there's
some interesting sort of data out there, including a study
that's being done in British Columbia where every woman who's
(25:21):
coming in to have her tubes tied just has their
tubes removed, and again the very early data suggests that
there's a decrease in ovarian cancer risk. We call that
an opportunistic salve in theectimy. So that I think nobody
should have their tubes tied anymore, you know, in the
general population or beer sacres, they should have their tubes
removed if they're using that for their family planning and
(25:44):
first control. The question becomes in beer sacres, how certain
are we about this? Because again, ovarian cancer has no
effective screening and Most women who are diagnosed with ovarian
cancer are diagnosed at elite stage, and most women with
a late stage ovarian cancer die of their disease. So
this is where the challenge is. The studies are ongoing,
but when will we feel strong enough to recommend that
(26:06):
as a routine care when we know how bad ovarian
cancer is. Right now, again, we don't have data sufficient
to tell people that they can avoid having their ovaries removed.
So what we're seeing more and more of is that
a b r C one Karen might have her twos
removed at thirty five and then her ovaries removed at forty.
For a br C two care, that's more like forty
(26:27):
and forty five.
Speaker 1 (26:28):
When do you think that data is going to be
mature five years, ten years, twenty years.
Speaker 3 (26:32):
Here's my worry that if people are getting their twos
removed at thirty five and then they still get their
ovaries removed at forty one, we won't have the data.
People have to keep their ovaries in long enough for
us to prove it works right sort of past forty
five or even un till each fifty. And I think
this is the tension I always have in the clinic
(26:54):
I'm really a clinician. First, I'm taking care of my patients.
I'm a bit of a researcher. Second, for my patients,
I don't want her to keep her overrays in. But
from a research perspective, and less enough people continue to
keep their ovaries, we're not going to have the data.
So I think it's going to be a little bit tricky,
and it might be a little bit entirely.
Speaker 1 (27:15):
Once I found out that I was a Brocco one carrier,
the decision to remove my uterus, ovaries and fallopian tubes
for me was straightforward. I was older, I'd already had
children and experienced menopause. For younger women, making the same
choice means two things. First, no further chance to conceive,
(27:36):
and second, entering menopause overnight. These are big decisions and
surgery might not be the best course of action for everyone.
When we come back from the break, we'll discuss other
preventive strategies for women to lower their risk, and we'll
talk about some groundbreaking new treatments on the horizon. More
from my conversation with Darja Susan Domchek in just a moment.
(28:11):
Welcome back to the show. I'm speaking with doctor Susan
damchek All about genetic testing. Her work is at the
forefront of cancer prevention, cutting edge strategies that seek to
stop cancer in its earliest stages. But before we get
to that, I wanted to ask doctor Domck about some
newer methods for identifying genetic risk. Let's move into just
(28:33):
the different types of genetic testing that are out there
now in terms of polygenic risk scores and whole genome sequencing.
Can you speak to these newer forms of genetic testing
a little bit?
Speaker 3 (28:42):
Sure, So let's start with polygenic risk scores. And but
that is a single alteration in FUERCA one increases your
risk of breast cancer by up to seventy percent. It
increases your risk google veering cancer up to forty five percent.
Polygenic risk scores look at small, little changes throughout your DNA.
(29:03):
The challenges of polygenic risk scores are that they're very
dependent on ethnicity, and so in the United States when
people are often sort of ethnically diverse, we haven't really
figured it all out yet. Okay, So moving on a
whole genome. So what is that? So, just as a reminder,
we have a certain number of genes over twenty thousand.
(29:26):
But when we test for genetics astibility, what we usually
do is focus on genes known to be associated with cancer.
So that can be a twenty five gene panel or
an eighty gene panel or something like that. There is
an approach that you can take called whole xome sequencing,
which just sequences the known genes, but it sequences all
the nome genes. And then there's whole genome sequencing, which
(29:50):
sequences the whole genome. If you do a whole xome sequencing,
you will find stuff. Most of us have stuff. The
question then becomes does that stuff matter? And it might
seem obvious that that stuff should matter, right that if
you find something that it obviously should matter. But it
turns out that genetics is not that simple as we
(30:13):
sometimes say. Genetics is not destiny. Just because you have
an alteration in some finding doesn't mean that you're going
to get that condition. And there are a lot of
genes where the risks associated with those genetic mutations aren't
very high. An example I'll give is something called SDHA
alterations in that gene predispose you to certain types of
(30:34):
rare tumors, but the risk of that happening if you
have an SDHA mutation is less than five percent. So
if we identify someone with that, generally speaking, we don't
do anything about it unless there's a family history consistent
with it. I'm only using that as an example to
show how you can get into trouble with things like
collexm and whole genome sequencing, which is we're going to
(30:57):
find a lot of stuff, but we won't necessarily know
exactly how to use it for that individual patient.
Speaker 1 (31:03):
Let's move into prevention strategies, right for the woman who's
not ready for prophylactic surgery, undergoing some screening, birth control pills,
even life style. What are the impact of these strategies
for women who carry brocka wan and Brocketo mutation.
Speaker 3 (31:15):
I think lifestyle is you know, the effects in berca
in one and two mutation carriers may be modest, just
because the genetics stuff is driving a lot of the risk.
Having said that, healthy weight, minimizing alcohol, regular exercise, not smoking,
these are all excellent things to do for women. There's
a lot of debate about what safe level of alcohol is,
(31:36):
but there has been some suggestion that you know, up
to three drinks a week. The risk is very very low,
so that's lifestyle always a good thing to do. The
data for medications such as tamoxifin, loxifen, and another drug
called exemesting in terms of decreasing the risk of breast
cancer is limited in beer CA carriers, although it does
seem like there is an impact in terms of ovarian
(31:58):
cancer risk reduction. Oral contraceptive pills do seem to decrease
the risk of a virile cancer. They also do slightly
increase the risk of breast cancer, so it's a risk
benefit decision. People have endometriosis or terrible heavy bleeding or
just really terrible cycles in general, and birth control pills
are really helpful or they need birth control, and particularly
(32:21):
in this day and age in the United States, it's
really important that people have access to affective birth control.
So the birth control discussion with the risk benefit profile
just needs to be individualized, so no easy answers there.
We're obviously really interested in other approaches, so this new
era of getting people better options is super important.
Speaker 1 (32:42):
Screening strategies, so breast screening is pretty well established with
MRI mammogram ultrasound ovarian cancer screening a mind filled anything
that you're excited about.
Speaker 3 (32:53):
Oh, varian cancer screening, it's just so difficult. As you know,
we've been through other blood tests in the distant past, overshore,
overseek over one, and I don't even remember all the
OVAs that came and went over the years that weren't
good tests. You know, I think that these new multi
cancer early detection tests are interesting but as yet unproven
and ovarying cancer early detection. This is why, unfortunately everyone
(33:18):
feels so strongly still about removal of the oversease. It's
because we don't have this well established the issue of
transnagal ultrasend. They really just don't work very well at all,
and there's a lot of false positives associated with them
because pre menopausal women have all sorts of cysts depending
on the timing of their cycle. So you know, the
(33:39):
guidelines have sort of been all over the map given
the absence of data. But a common strategy is to
start ovarian cancer screening sort of at the time you
would start considering removal of the ovarias, so like thirty
five for BARC one or forty for br C two,
in which case a false positive that led you down
to removal of the ovarias. I'm not saying is not
(34:00):
so bad because it's we're still taling with the impact,
but it's in the range that we would consider that.
So I'm curious about your approach to it, but that's
often the approach that we take in the absence of
better data.
Speaker 1 (34:11):
I'm looking forward to research and development of new screening tools.
I think that you know twenty five ultracent. We use them,
employ them, but realize that they're limited. But as the
best we can do. Have to be super careful though
in terms of caution, interpretation of results, really really really careful.
But I want to get into your really exciting work
(34:32):
with cancer interception and cancer vaccines. You know, our family
history is pancreas cancer. You can't take out you're pancreas,
and screening for pancreas cancer is limited and not well proven.
So talk to me about cancer interception and cancer prevention vaccines.
Speaker 3 (34:47):
Yeah. Sure, So this phrase cancer interception, what does it
even mean anyway, It's a way to try to differentiate
from prevention. You know, when we talk about prevention, if
it's a little bit like you don't smoke because smoking
causes those changes that lead to cancer. Right, So prevention
is you don't smoke, so you don't even start those changes.
Cancer interception, which was going by Loose Blackburn and no
(35:11):
prize winning scientists. It's trying to target the earliest stages
of cancer development. The cancer has just started, but you
can't detect it yet, and so that's cancer interception. So
the idea here is that we try to target those
first cells that are turning into cancer in a beer
C carrier, so maybe I've lost the second copy of
beer C for instance. So when you think about potential strategies,
(35:35):
one of those strategies could be immune interception. So we
really have a better understanding over the last you know,
fifteen plus years that the immune system is incredibly important
in cancer in a way that would have been you know,
laughed at twenty five years ago. But we know that
we can use immune therapies to help treat cancer. So
(35:56):
one of the strategies that we're trying is to develop
a vaccine that might develop immune cells that find those
earliest cancer cells. You know, they're surveying your body and
then as soon as that cell develops, they they target
it and kill it. So we recently completed a study
where we did vaccinate healthy BRC carriers using something called
(36:17):
the DNA plasmid vaccine. What we were vaccine two isn't
specific to BRC carriers, but it's the idea that you
could identify a group that's at a high enough risk
to try this. So the vaccine was safe, and now
we're waiting to get the imminology results and then figure
out our next phase. So that's sort of one approach.
Let's use the immune system, let's target different types of
(36:41):
immune strategies. We are also looking at mRNA types of
approaches to vaccines. I mean, I do not view vaccines
as a dirty word here, but if you want to
call it immune interception as opposed to vaccines, I'll take
that as well. But there's other ways to think about interceptions.
So let's talk about pancreatic cancer. Pancreatic cancer. The risk
(37:01):
of pancreatic cancer's highest in br C two rather than
BRC one mutation carres, although the risk is elevated in both,
and as you said, pancreatic cancer is a tough cancer.
We do offer screening with either a endoscopic ulture sound
or abdominal MRI, but as you mentioned, you know, it
is limited, but almost all pancreatic cancers develop something called
k Wrass mutations. So we actually also have work being
(37:25):
done in the pass Or center looking at whether or
not k wrass inhibitors in mice can decrease the risk
of developing pancreatic cancer. So those are some some of
the ideas that we have. There's other work going on.
Could we use short doses of apartment hit er, these
drugs that we use in the advanced cancer setting and
in high risk breast cancer setting, could we use those
(37:47):
intermittently to if you will, weed the garden and take
out all those weeds before they develop into something, right,
intermittently getting rid of all of those pre cancerous cells.
So more to come, but it's a really exciting area
that we're working on.
Speaker 1 (38:03):
If listeners could take away one point from this conversation,
what would you like it to be to.
Speaker 3 (38:09):
Be proactive about getting your family history taken seriously? I
think that patients can be, if you will, a little
put off and be like, oh, don't worry about that.
That's not enough to get genetic testing. And the fact
is is that most doctors out there learned about genetic
testing in medical school, you know, fifteen or twenty years ago,
(38:30):
and they're not entirely up to date. It's not their fault.
There's too much to do. But there's a lot of
resources out there, and you can self refer to a
genetic counselor to get more information if you're not getting
the answers that you want.
Speaker 1 (38:43):
Are there resources for our listeners actually in terms of
where they can go to learn more about this.
Speaker 3 (38:49):
Yeah, we do at faster dot org so BA s
ser dot org. We have a lot about why genetic
testing can be helpful and have provided some resources, including
any large comprehensive cancer center will have genetic counselors available.
There are plenty of physicians, gecologists, and primary care directors
(39:10):
who comfortable with this and do you do it? So
asking your primary care doctor first can always make sense,
But if your primary care doctor doesn't know a lot
about it or it's not really offering it to you,
don't stop there. There are lots of different ways to
get this done.
Speaker 1 (39:29):
I had cancer and I had seen some of the
best physicians in the country for treatment. None of them
ever mentioned to me genetic testing. I am literally a geneticist,
and I didn't think that this applied to me. If
you have family members with breast ovarian, pancreatic, or prostate cancer,
it's worth it to consider genetic testing, even if your
(39:51):
doctor hasn't suggested it, Even if you've been tested in
the past a ten years or so, I'd recommend thinking
about testing again. Technology is getting better and better each day.
We're aware of more cancer causing genes than we were
a decade ago, and we have more tools to treat
those specific diseases. Your health insurance may cover genetic testing
(40:12):
if you fall into a high risk group, but if not,
there are lots of alternative ways that you can get
genetic information you need. Direct to consumer options like I
did are quick and easy, but I would always recommend
connecting with a genetic counselor to help interpret your results.
If you are positive for genetic mutation, there are a
multitude of preventative measures that you can take, from prophylactic
(40:35):
surgeries to risk reducing drugs like tomoxifen or reluxaphene. Ultimately,
you are responsible for your own health. You have to
advocate for yourself, but you don't have to do it alone.
There are amazing places like the beast Or Center that
can help you navigate this, Organizations that have testing, genetic counseling,
(40:56):
treatment options, and positive communities all in one place. Taking
that first step could save your life or the life
of someone you love. Coming up on the next episode
of Decoding Women's Health, I speak with a world renowned
(41:16):
expert in medical cannabis. You are not going to want
to miss this one.
Speaker 4 (41:21):
The top three indications for medical cannabis use across the
country are chronic pain, mood or anxiety, and sleep disruption.
Not surprisingly, these are the three top conditions we hear
about in individuals who are either perimenopausal or postmenopausal.
Speaker 1 (41:35):
Decoding Women's Health is a production of Pushkin Industries and
the Atria Health and Research Institute. This episode was produced
by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid,
mastering by Sarah Buguer. Our associate producer is Sonia Gerwit,
backchecking by doctor David Dodick. Our executive producer is Alexandra Garreton.
(41:57):
Our theme song was composed by HANNS. Brown. Concept and
creative development by Shavn O'Connor. A special thanks to Alan
Tish David Saltzman, Sarah Nix, Eric Sandler, More Ratner, Amy Hagdorn,
Owen Miller, Jordan McMillan, and Greta Cohne. If you have
(42:18):
questions about women's health and midlife and want expert advice,
leave us a voicemail at four FI five two oh one,
three three eight five, or send us a message at
Decoding Women's Health at pushkin dot FM. I'm doctor Elizabeth Pointer,
and thanks for listening. Until next time,
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