Hereditary Cancer Syndromes: The Major Players and How to Identify Them

Name: Hereditary Cancer Syndromes: The Major Players and How to Identify Them
Uploaded: 2021-10-22T13:16:57.547Z
Duration: 1 h 8 min 21 s
Description: A CME Program with the Smilow Cancer Genetics and Prevention Program Presentation by: Amy Killie, MS, CGC

October 22, 2021

A CME Program with the Smilow Cancer Genetics and Prevention Program

Presentation by: Amy Killie, MS, CGC

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00:00Well, I think we'll get started
00:02up so my name is Claire Healy.
00:05I'm one of the managers in this
00:07Milo cancer genetics and prevention
00:09program and we're very excited to
00:11have all of you join us tonight.
00:13This is a two night seminar series
00:16and we've titled it Identifying and
00:18caring for individuals with high
00:20risk and inherited cancer syndrome
00:23and the goal of this seminar series
00:25is really to help provide some
00:26information to our colleagues in the
00:28community on how to recognize patients.
00:30At elevated risk to develop cancer
00:33and that those who may have an
00:37underlying hereditary cancer risk.
00:38There will be utilizing their
00:41Q&A feature for questions,
00:42so feel free to type your questions
00:44in as the talks goes on and we will
00:48plan to have a question and answer
00:50session at the end with our speaker,
00:53so I'll introduce our speaker
00:54and then turn things over to her.
00:56So tonight we're pleased to welcome
00:58Amy Kelly and Amy received her Masters
01:01degree in genetic counseling from the
01:04ICANN School of Medicine at Mount Sinai.
01:06This band with a smile.
01:07Oh cancer genetics and prevention
01:09program for four years and she's one
01:12of our more experienced counselors
01:14at a genetic counselor to level
01:16and her research interests include
01:18hereditary pancreatic cancer.
01:20So we're thrilled to have Amy and
01:22Amy thank you for joining us.
01:23I'll turn it over to you.
01:27Great, thanks so much Claire
01:29for the introduction.
01:30Good evening everyone.
01:32I'm very excited to be talking
01:34to you about hereditary cancer
01:35and things to look for and things
01:38to consider when thinking about
01:40a referral to harass her cancer.
01:42So I am just going to share my screen.
01:59Amy, I'm not seeing your slides. Yep,
02:02I just put it on pause just for one. OK.
02:08And.
02:13These things always take a second day.
02:15OK, there we go. Great OK perfect.
02:22So just for the agenda today,
02:25what I want to go over as I want to review
02:28referral guidelines for hereditary cancer,
02:30I want to review the more common
02:33hereditary cancer indications.
02:34Then I want to review a couple of more
02:36rare hereditary cancer indications,
02:38then talk about self pay,
02:40genetic testing and also direct
02:41to consumer genetic testing and
02:43talk about some of the practical
02:45practical aspects of genetic casting.
02:47Why someone may want to have genetic
02:50testing and talk about genetic counseling.
02:53As a whole.
02:55So to start talking about
02:57hereditary breast cancer,
02:58so we cannot talk about hereditary
03:01cancer without talking about BRCA
03:03one and BRCA 2 related to hereditary
03:06breast and ovarian cancer syndrome.
03:09These genes are probably the poster
03:12children of hereditary cancer
03:14testing and I know that everyone
03:16here has heard about them before.
03:18As we know they make up mutations
03:21in these genes.
03:22Germline mutations in these genes
03:24are associated with a high risk of
03:26breast cancer in women which depends
03:28slightly dependent on BRCA one or
03:30BRCA 2 but the risk is between 50
03:32to 75% lifetime risk and also a
03:34significantly increased risk of
03:36ovarian cancer in women with again
03:39arranged depending on the gene but
03:41between 15 up to 60% lifetime risk.
03:44So definitely significant lifetime risks and.
03:48This this I mentioned.
03:50These jeans are the poster children
03:51of why we do genetic testing.
03:53Is that even though these are
03:55considered to be high risk genes,
03:56there are management guidelines.
03:58There's screening options for women
04:00who test positive for a mutation,
04:02BRCA one and BRCA 2 in terms of beginning
04:06breast imaging at a younger age.
04:08Adding on breast MRI for more
04:11sensitive imaging.
04:12Prophylactic bilateral mastectomy's.
04:13I feel like they're often talked
04:15about in the media at once.
04:17Part of Angelina Jolie.
04:18Is an option women decided to pursue and
04:21of course and of course prophylactic
04:23bilateral salpingo over ectomy to be
04:25preventative against ovarian cancer.
04:27So in the advent of genetic testing for
04:30these genes and establishing guidelines
04:32you know women and other people
04:34who are at higher risk of pressure,
04:36right cancer have really been able
04:38to take this information and use
04:41it to actually lengthen their life
04:43and have a better quality of life.
04:45So really we can't.
04:46We can't talk about hereditary
04:47cancer without talking about these.
04:492 genes.
04:51However.
04:53We are now past the era of only
04:56testing BRCA one and BRCA 2.
04:59It's not uncommon for me to see a
05:02patient and say oh I'm here for the
05:05the Braca test but now you know,
05:08especially since about 2015 now.
05:12Our testing includes many other genes
05:15that we now know of relating to
05:18hereditary risk of breast cancer and
05:21we know that these genes they they
05:23can be arranged so some of these.
05:25And broke up a little categories
05:27but BRCA one and two are related to
05:30are considered a high risk breast
05:32cancer gene and there's other
05:33genes that fall into that
05:35category as well that also have guidelines.
05:38Now some of these higher risk
05:40genes often have other features
05:42that are uncommon or more rare.
05:44For example, the gene TP 53.
05:47Many people have heard of related
05:49to leave from many syndrome which is
05:51most characteristic of early onset
05:54sarcomas or early onset osteosarcomas.
05:56Very young breast cancer
05:58in childhood cancers.
06:00So not every single high risk gene is
06:03necessarily a gene of interest for a
06:06woman who has early onset breast cancer.
06:08But with the advent of larger
06:11testing we can now test for these
06:13genes all the same time.
06:15And what we now know is there are
06:17other genes that fall into more of the
06:20moderate risk which would be ATM and CHEK 2.
06:23You can see in the middle and the
06:25blue column there you know the risk.
06:27Ranges between 20 to 40% lifetime risk.
06:29You can see in the high risk category PAL B2,
06:33which has been in the news.
06:34More recently we're getting a
06:36lot of messages about PAL B2,
06:38but we consider to be a moderate
06:40to high risk breast cancer gene,
06:42which is why it's in the high
06:45risk category where the risk can
06:47be upwards of 58% lifetime risk.
06:49So there are other genes that
06:51we definitely want to be testing
06:54individuals for if they have a family.
06:57History that's concerning.
06:58For hereditary breast cancer.
07:00And now there's you see in the green
07:02the green column there are genes
07:04that have an unknown risk of breast
07:06cancer because as we've studied genes,
07:09and as we've learned more about genes,
07:11the risk is sometimes unclear where the
07:13there might be literature suggesting
07:15an increased risk of breast cancer,
07:18but maybe not enough to be
07:20significant or more data is needed.
07:22So some of these genes we off
07:25we can are included on genetic.
07:27Testing and this again just just
07:31shows the range.
07:32Specifically,
07:32I would say the the major ones that
07:35we would test for like ATM Chek 2,
07:37PALB 2,
07:38where the the lighter blue is the
07:40higher end end of the range and
07:43the darker blue is the lower end
07:45of the range so you can see.
07:48Regina is different and that's
07:51that's why we're now past this
07:52era of only doing testing for BRCA
07:54one and BRCA 2 because these genes
07:57some of them do have significant
07:59risks and most importantly we have
08:01guidelines for screening.
08:04Now this is sometimes a very common thing
08:07that we will see with with patients.
08:09Usually 1-2 testing has been
08:12around for at least 20 years,
08:14so it's not uncommon for for patients to say,
08:17oh, I've already had this test.
08:19I had this test in 2012.
08:21It was it was negative,
08:23so I was often common to see
08:26a test report like this.
08:28But back before I would say
08:31definitely before 2014 and probably
08:33a little bit even before then.
08:36Specially BRCA one and two testing
08:38was really limited to sequencing
08:41only and sequencing for BRCA one
08:44and BRCA 2 can detect up to 80% of
08:49detectable pathogenic mutations and
08:52sequencing covers the clinically
08:54important regions of each gene,
08:55including the coding exons,
08:57so that is that is a very informative
09:00test but sequencing cannot detect
09:03large deletions or duplications.
09:06Of your C1 and BRCA 2 so it is
09:09important when a patient has had
09:11genetic testing to know what year
09:14was it and also confirmed with
09:17records because for example in this
09:19case it says BRCA one and BRCA
09:221 sequencing BRCA 2 sequencing.
09:24No mutation detected but this test
09:27would not include what we consider
09:31large rearrangement analysis.
09:33Which is on,
09:34but you can say he see here BRCA one
09:37and BRCA 2 full gene rearrangement also
09:40sometimes called deletion duplication
09:42which detects intragenic deletions
09:45and duplications at at single exons.
09:48Some people also call this a the
09:51Bart test because back until 2013,
09:55Myriad Genetics had the patent
09:56on BRCA one and two,
09:58so their actual test name for BRCA one
10:01and two large rearrangement testing.
10:04Was Bart so some people might.
10:07You might hear patients talking
10:08about bar testing.
10:09You might hear about bar testing.
10:11Bart is just a name that Myriad gave
10:15their own tasks for large rearrangement.
10:18But now that Myriad Genetics
10:20don't have the patent,
10:21there's plenty.
10:22There's many other labs
10:23doing doing this test,
10:25and nowadays it's standard
10:26of care when we do.
10:28BRCA one and two testing to do full gene
10:31sequencing and deletion duplication.
10:34So what's also important is
10:36that if a patient reports BRC
10:39wanted to testing prior 2013,
10:41one is possible they may have only
10:44had BRCA one and two sequencing
10:46and not deletion duplication.
10:48But even if they had full gene
10:51sequencing and deletion duplication,
10:53updated genetic testing is likely
10:55to be indicated because prior
10:572013 those other genes I had
11:00talked about related to hereditary
11:02breast cancer were not included.
11:04On genetic testing,
11:05or at least very rarely included.
11:08So if patients before 2013 say
11:11that they had negative testing in,
11:14likely is worth or a new referral
11:16to talk about updated testing,
11:18and they say 2013.
11:20But even patients that 2014,
11:222015 some of these bigger tests,
11:25these bigger panels were still
11:27coming into play,
11:28but I would say anything before 2013
11:31is definitely worth a new evaluation.
11:34So I'm talking about hereditary
11:35breast cancer. So what?
11:37So what should?
11:38What should you be thinking
11:39about what I would indicate
11:41a referral to cancer genetics?
11:42If we're thinking about
11:44hereditary breast cancer?
11:45So our bread and butter for
11:48guidelines is NCCN guidelines.
11:50Based from the National
11:52Comprehensive Cancer Network,
11:53and these guidelines change every 6
11:55to 12 months before it was focusing
11:58on just pure C1 and BRCA 2 but now
12:01in the advent of panel testing,
12:04moving past the era of just BRCA 1.
12:06And BRCA two we know there are
12:09other genes if someone would
12:11meet clinical guidelines for so.
12:13NCCN used to have a nice package
12:16of just BRCA one and two relating
12:19to hereditary breast cancer.
12:21But now they've broken it up a little
12:24bit into hereditary breast cancer genes,
12:27hereditary ovarian cancer genes correct,
12:30right?
12:31Pancreatic cancer genes and
12:32hereditary prostate cancer genes.
12:34The reason for this is because.
12:36Mutations in BRCA one and BRCA two
12:39are related to hereditary breast
12:41cancer and ovarian cancer in women
12:43and and breast cancer in men but
12:46also they are related to prostate.
12:48Cancer risk in men and pancreatic
12:51cancer risk in men and women.
12:53So that's why NCCM has so many guidelines.
12:56And definitely it's not.
12:58These are in.
12:59Again, they change every 6 to 12 months,
13:00so you are not expected to be
13:02the expert on these guidelines.
13:04Again,
13:05as cancer genetics,
13:06we want to be a resource to you
13:09for your patience.
13:10So just to really distill some of
13:12these guidelines down and just some
13:15suggesting subjects things to think
13:17about when placing a referral.
13:19Is that if someone with a diagnosis
13:23of breast cancer under 50,
13:25anything premenopausal?
13:26I will say you know there there
13:30isn't blue for for testing if
13:32someone is at 50 or at 49 with
13:36no other family history.
13:37It's possible this possible they may
13:39not meet their insurance guidelines
13:41to be protesting to be clinically
13:43indicated and meet insurance guidelines.
13:45Someone would need to be
13:48diagnosed at 45 or younger.
13:50But the reason why I posted before
13:5250s because it is worth a referral,
13:54because sometimes there may be
13:56other factors that we would
13:58want to look into in the family,
14:00including small family size or
14:02limited structure or and also also
14:04just to go through more distant
14:07relatives and take the time to go
14:09through a whole family history.
14:11Now NCCN guidelines recommending
14:13genetic testing for anyone with
14:15triple negative breast cancer at
14:18any age and triple negative breast
14:20cancer is breast cancer that test
14:22negative for the estrogen receptor.
14:24Progesterone receptor and access
14:26of the her two protein.
14:29So this means essentially that the
14:31growth of the cancer is not fueled by
14:33the hormones estrogen and progesterone,
14:35and is also not fueled by the
14:37her two protein.
14:38So triple negative breast cancer tends to be.
14:41Much harder to treat and more
14:43aggressive because it does not
14:45respond to hormonal therapy, so.
14:47NCCN guidelines is now recommending
14:50triple negative breast cancer at any age.
14:53Because triple negative breast
14:54cancer is more likely to have a
14:57hereditary component than non
14:59triple negative breast cancer.
15:00For for most insurance purposes,
15:03since insurance tends to be slower
15:05on the uptake than guidelines
15:07that change every 6 to 12 months,
15:09insurance won't cover testing and
15:11without any other family history unless
15:14someone is diagnosed at 60 or younger.
15:16So something to keep in mind,
15:18but for in terms of a referral, it is def.
15:21I would say indicated,
15:23so something that we can
15:25talk about with the patient.
15:26Anyone with ovarian flopping to her primary
15:30parotta Neil Cancer at any age is genetic.
15:32Testing is indicated.
15:34Men diagnosed with breast cancer at any age.
15:37Metastatic intraductal prostate cancer
15:39diagnosis at any age and this is a
15:42more I would say a newer development
15:45within the last two years where there's
15:47been literature has suggested that
15:49men who have meta static or prostate
15:52cancer that's more locally advanced,
15:55particularly if it's a higher Gleason score.
15:57Which is used to rate aggressiveness
16:00of the prostate cancer.
16:02There is a higher prevalence of
16:04germline mutations in that group,
16:05so that's why for men with metastatic
16:08or intraductal prostate cancer,
16:09regardless of their AIDS,
16:11genetic testing is indicated,
16:13particularly since it can be helpful
16:15in their own treatment options.
16:18Same thing with pancreatic cancer.
16:19This is a relatively new development
16:22since about 2019.
16:23I guess it's not so recent, but all things.
16:26But when I started in order
16:28for pancreatic cancer to be,
16:30someone meet criteria,
16:31they will need additional family history,
16:34which is now not the case.
16:36Pancreatic cancer based on newer literature,
16:38kind of similar to metastatic
16:41prostate cancer,
16:41is more likely to have a germline
16:44mutation than more common cancers,
16:46so given that.
16:47If so,
16:48given that that's why pancreatic
16:50cancer at any age is clinically
16:53indicated for genetic testing.
16:55Also, because there is treatment options.
17:00And also,
17:00if there's three cases of the same
17:03cancer or or associated cancers
17:04on the same side of the family,
17:06so someone who has breast cancer and
17:09two relatives with breast cancer or
17:12someone with breast breast cancer,
17:14some cousin with ovarian cancer,
17:16someone,
17:17a man with prostate cancer and
17:19his mother with breast cancer.
17:20So those cancers all in the family is.
17:23If you were seeing that especially
17:25multiple generations,
17:26multiple relatives is definitely worth over.
17:30Referral.
17:32And finally,
17:33someone who has multiple primary cancers,
17:35such as someone who has breast and
17:38ovarian cancer and bilateral breast cancer,
17:41may be worth the referral.
17:43Bilateral breast cancer if there's
17:45no other family history and with
17:47depending on the age and may not meet
17:50insurance criteria for genetic testing,
17:52but it is worth a referral just for us
17:55to fully flush out the family history
17:57and talk about that with the patient.
18:02So this is similar to the previous slide,
18:05but for just those patients with
18:07only a family history of cancer.
18:09Something to consider is someone
18:11who is Ashkenazi Jewish ancestry,
18:13one in 40 individuals of Ashkenazi
18:16Jewish ancestry will have a
18:18BRCA one and BRCA 2 mutation.
18:20There are three founder mutations
18:23that are seen very commonly
18:25in the Ashkenazi population.
18:2895% of Ashkenazi Jewish
18:29individuals who have a BRCA 1.
18:32Or BRCA 2 mutation will have
18:34one of these three mutations.
18:36So it is more common in the
18:39Ashkenazi population while in the
18:40non Ashkenazy population the risk
18:42of a BRCA mutations about one in
18:45400 so is significantly increased.
18:47What I will say is that without a
18:50family history of breast cancer,
18:52ovarian, prostate cancer,
18:54pancreatic cancer,
18:55the likelihood someone would have
18:57a mutation is still relatively
18:59low and at this point in time
19:00there is no recommendations.
19:02For general screening of the Ashkenazi
19:05Jewish population without a family history,
19:08so it is something I think worth
19:10to consider for a referral,
19:12because at least then we can talk about
19:14with the patient and we can go through,
19:16go through the family history.
19:17But I do want to make that caviar.
19:21Kind of similar to the before slide,
19:22if someone has at least three breast
19:25cancers in the family and their,
19:28you know in their mother and their
19:29aunt and a cousin again clustered
19:31on the same side of the family,
19:32that was worth the referral.
19:35Someone who has a close relative
19:37with breast cancer diagnosed at 45
19:40or younger is worth a referral.
19:41And someone who has a relative
19:44with ovarian cancer.
19:45Someone if someone reports out there on
19:48how to ovarian cancer that individual
19:50does meet criteria based on family history.
19:53Same thing with male breast cancer.
19:55Having an uncle or father with male
19:58breast cancer is a referral is indicated.
20:01Pancreatic cancer in a close relative,
20:04particularly if specifically
20:06if it's apparent.
20:07For a child or a sibling that is
20:09worth a referral and same thing
20:12with metastatic prostate cancer.
20:14This in a close male relative.
20:17And finally, as before.
20:20Leave any close relatives with a
20:21combination of the above cancer types.
20:23Again, if you're seeing in the same family,
20:26prostate, ovarian, breast,
20:27pancreatic, any combination of that,
20:30that is definitely worth a referral.
20:32'cause cancers all can be associated
20:34through a single gene mutation.
20:37Now switching gears and going
20:38to her age right colon cancer.
20:40Kind of like with hereditary breast cancer.
20:42We cannot talk about her age rate colon
20:45cancer without talking about Lynch syndrome.
20:47Lynch syndrome is caused by germline
20:49mutations in one of the five,
20:51so we one of the four mismatch repair
20:54proteins or deletions in the Epcam gene.
20:57The risk is very dependent upon the gene,
21:00especially in the last few years.
21:02We've actually realized that the lifetime
21:04risks with specifically with mutations.
21:07And TM,
21:07S2 and MSH six are quite different
21:10than the risks associated with them.
21:12Which one and MSH.
21:132 and that could actually be
21:15a whole whole talking in of itself.
21:17So I'm not going to go into all the
21:19details of how they're different,
21:21but essentially the main cancer risks
21:24with Lynch syndrome is colorectal cancer
21:28and uterine or endometrial cancer.
21:30As you can see in this chart,
21:32which is mainly based on the high,
21:34I would say the more high
21:36penetrance genes Emily Quan and H.
21:38Two, but there are risk of
21:40other types of cancers,
21:41including other GI cancers like
21:43cancer of the stomach file,
21:45duct cancer of the pancreas.
21:48You can also see ovarian cancer
21:49and women who have Lynch syndrome
21:52and cancer of the urinary tract,
21:54like the bladder and also individuals
21:56with Lynch syndrome can have sebaceous
21:58adenomas which are very specific
22:00types of skin of skin findings.
22:05So when we think about hereditary
22:07colon cancer, I often think about in
22:09these two buckets where one bucket is
22:12what we call nonpolyposis syndromes,
22:14which essentially is mainly Lynch syndrome,
22:17maybe other hereditary
22:18colon cancer syndromes.
22:20This just means that someone is at a
22:23high risk genetically of colon cancer,
22:26but it's not necessarily because they're
22:29developing a large number of polyps.
22:32The polyps and Lynch syndrome
22:33are not numerous like with.
22:35Polly process,
22:36but the polyps in Lynch syndrome
22:38do advance much faster than non
22:41lynch syndrome associated polyps.
22:43So nonpolyposis syndromes you would
22:45see a high risk of colon cancer but
22:48not the high risk of numerous polyps.
22:51Poly Post syndromes are different
22:54because an individual would be
22:56genetically predisposed to developing
22:58large number of column of colon.
23:01Polyps depend.
23:02The type is dependent on the the
23:04polyposis syndrome and I will.
23:06Review those briefly on the next slide,
23:08but typically they polyps tend
23:10to be numerous, usually over 10,
23:13and that numerous those numerous
23:15polyps or what's causing the
23:17increased risk of colon cancer.
23:21So hurry, Polly pulses syndrome.
23:23Most people have heard about familial
23:26adenomatous polyp ossis or FAP
23:28which is characterized by someone
23:30developing in the classic form,
23:32developing hundreds,
23:34possibly up to 1000 adenomatous colon
23:37polyps beginning at a very young age,
23:40usually in the 20s and 20s.
23:42Eat or even younger and for
23:45the majority of individuals.
23:47If this was left untreated,
23:49it's with with a total colectomy.
23:52There would, uh,
23:53the risk of colon cancer
23:54approaches 100% even by age 40,
23:57so this is a significant
23:59Poly pulses syndrome,
24:00attenuated as as the name implies,
24:03is attenuated,
24:03meaning that the polyps develop
24:05at a later age and there can
24:07be a smaller number of polyps,
24:09such usually over usually over 12
24:12/ 20 up to 100 adenomatous polyps,
24:16usually beginning in the 30s or 40s
24:19fifties and we have seen a variety of.
24:22Even very attenuated forms
24:24even in our own clinic.
24:26So there does appear to be some
24:28variability we're discovering map can
24:31sometimes mimic attenuated faps UM,
24:34but the only difference with that is
24:36that the all the cancer syndromes I've
24:39talked about or autosomal dominant,
24:41meaning someone would need to inherit a
24:44single pathogenic variant in one copy
24:46of the gene map is autosomal recessive.
24:49So for someone to have map,
24:51they would need their parents,
24:52we need to be carriers.
24:54In math,
24:54is can present in a similar way too,
24:57attenuated faps with again over,
25:00usually over a dozen polyps up to
25:03100 polyps beginning in someones 40s
25:05or or 50s Paula Mac and sometimes
25:08present with a more mixed Poly
25:10poesis type where there's adenomas
25:13but also non adenomatous polyps
25:15like hyperplastic polyps and others.
25:17Play Seeger syndrome is a is
25:20A is a rare syndrome.
25:23It presents particularly with
25:24Poly pulses of the small bowel.
25:27You could also see it in the colon,
25:29but the small bowel is the
25:30part that's mostly affected.
25:32They develop specific pretty agurs polyps.
25:34There's other features such as
25:37Miko cutaneous pigmentation
25:38that's present in childhood around
25:40the lips on the fingertips,
25:42even on the nostrils,
25:44and there isn't also associated risk
25:46of breast cancer and pancreatic cancer.
25:49Juvenile polyp Ossis syndrome is
25:51not related to the age of onset of
25:55polyps because is not necessarily mean.
25:58Someone develops polyps as
25:59a juvenile or a child,
26:01but the these individuals develop
26:03specific types of juvenile polyps
26:06and juvenile polyps are not.
26:08They're not common types of polyps to have,
26:10so someone who presents with multiple
26:14juvenile polyps would warrant
26:16investigation or juvenile polipo SIS.
26:19And then there's other more newly
26:21described Poly closest Jeanswear.
26:23The risk there does appear to
26:24be some risk of of Poly poesis,
26:26but how that presents exactly is less clear.
26:32So since there are those,
26:33those two buckets,
26:34so let's talk about some of the the
26:36guidelines for the referral guidelines
26:38for her age right colon cancer.
26:40So Lynch syndrome and the guidelines
26:43on NCCN are a little bit more clear
26:47in terms of when to when to refer.
26:51I'm not going to go through all of
26:53this because I know it's a lot and
26:55I'm gonna again distill it down.
26:56But essentially it is based in a similar
26:59way to BRC wanted to based on the age of
27:04diagnosis and the number of people affected.
27:07Poly post syndromes.
27:08The testing strategy can be as you can see,
27:11branched off a lot so as to
27:13focus on this part here.
27:15Probably most important thing to
27:17think about is the number of polyps.
27:20It says here over 10 helps me.
27:23Over 20 adenomas.
27:24We sometimes are more conservative
27:27and if we see more than 10 adenomas,
27:30it's it's worth a referral just
27:32to look at the family history.
27:35If someone has exactly 10, you know,
27:38depending on their their age,
27:40how many colonoscopies they've had.
27:42Again, adenomas are common,
27:44especially if people get older.
27:45So having a few or a couple adenomas is
27:48not does not mean someone has Polly Pocest.
27:51But something to think about.
27:53Also, as someone's age.
27:54Also,
27:54the size of the polop a young person
27:57with a very large adenomas polyp,
28:00even with a single a single polyp,
28:02may still be worth worth the referral.
28:06But these are these are suggestions,
28:08so anyone with a colon or uterine
28:11and demetral cancer diagnosis
28:12under the age of 50 that would be
28:15specifically suspicious of Lynch
28:16syndrome because we expect to see
28:18those cancers at younger ages.
28:21Any Lynch syndrome associated cancer,
28:23that is microsatellite instable
28:26or has abnormal MMR staining
28:28by immunohistochemistry.
28:29So during it once now here at at a young
28:34and haven and offered other other places,
28:37they're now doing universal screening
28:40of colon and endometrial tumors,
28:44which is done through immunohistochemistry.
28:46So staining of of the tumor to look for
28:49the presence or absence of MMR proteins.
28:53For individuals who have Lynch syndrome,
28:55if we would expect that those MMR
28:58proteins would actually be absent
29:01on IHC staining and if those
29:03MMR proteins are absent,
29:05it actually results in
29:07microsatellite instability.
29:08So this is something that is
29:10on is on pathology.
29:11It would comment if there was loss
29:13or presence of these proteins if
29:16there was microsatellite instability.
29:18And so the presence of MMR proteins
29:21would actually be reassuring.
29:23And it actually would reduce
29:24the risk of Lynch syndrome,
29:25but that's why any cancer with
29:29abnormal IHC missing MMR proteins,
29:32regardless of age, is is warrants a referral.
29:36As I mentioned before,
29:38multiple or you know over over 10
29:41or early onset gastro GI polyps,
29:44particularly in the in the colon,
29:46but also again I mentioned
29:48with puts Jaeger syndrome.
29:50If there is or there are polyps of the
29:53small bowel that can also warrant a referral.
29:58And specifically,
29:59I would say over 10 adenoma
30:01dis or mixed Histology polyps.
30:04Meaning if someone had a mix of adenomas
30:07or other polyps like hyperplastic polyps
30:10that weren't warrant or referral.
30:13With since Hammertoe medicine juvenile
30:15polyps are more rare polyp types,
30:18if we if we see there's essentially
30:20a lower threshold
30:21for the number of those polyps.
30:23So seeing at least five of those polyps
30:25could warrant a referral and ***** aggers
30:28polyps are a particular type of colon,
30:30polyp or small bowel polyp,
30:33so if that is confirmed on pathology,
30:35at least two it definitely
30:38is warrants or referral.
30:40I'm adding this here for
30:41diffuse gastric cancer.
30:42It's not necessarily related to her edge,
30:44right colon cancer,
30:46but diffuse gastric cancer is
30:48a rare type of gastric cancer,
30:51and it actually can be related.
30:53It is related to win this
30:55hereditary related also to lobular
30:57risk of lobular breast cancer.
31:00So diffuse gastric cancer again is rare.
31:03A specific pathology,
31:05but definitely diagnosis under
31:0750 would warrant or referral.
31:10And similar to BRCA one and two,
31:12if there's three cases of the same cancer
31:16like 3 colon cancers or colon uterine colon,
31:20stomach,
31:20bladder, stomach,
31:21colon all in close relatives
31:24and multiple generations.
31:26You know looking for those associated
31:28cancers that would warrant a referral.
31:31And similar for another for BRCA one and
31:34two multiple cancers in one individual,
31:37such as someone who's had two
31:39colon cancers or someone who's
31:42had colon and any material cancer.
31:44For his patients with with just
31:46a family history of cancer.
31:48Again, as I mentioned before,
31:50someone with at least three colon
31:52cancers or Lynch syndrome associated
31:54cancers in first and second degree
31:57relatives so close relatives.
31:59At least one first of your relative
32:01with colon or endometrial cancer
32:02under the age of 50.
32:04So if someone's parent had color,
32:06sibling had colon cancer under
32:0950 or uterine cancer under 50.
32:12And for second or third of your
32:13relatives with a combination
32:14of the above cancer types,
32:16again looking for those patterns of cancer.
32:21So I'm I'm. I'm sure everyone here again
32:24as I talked about with knows about BRCA
32:26one and two Lynch syndrome Poly Pulsus.
32:29I want to talk about a few of more
32:31rare indications that you may not come
32:33across but just something I wanted
32:36to bring up as a rare indication.
32:38So hereditary paraganglioma and
32:40Pheochromocytoma syndrome is is very
32:43rare and as as the name implies,
32:47individuals or increased risk
32:49to develop rare tumor.
32:52Here is called Paraganglioma
32:54and pheochromocytomas,
32:56so they develop from specific
32:57nerve nerve cells.
32:58The the chromaffin cells and
33:00paragangliomas developed along the
33:02Para vertebral axis from the base
33:04of the skull to the pelvis so they
33:06can show up in the head and neck.
33:08They can show up in the abdomen.
33:10Pheochromocytomas are a specific
33:12type of paraganglioma that is
33:15confined to the adrenal medula.
33:18Both of these tumors can
33:20secrete calcaneus specifically.
33:22Feos almost always secrete
33:24these excess of hormones,
33:27so someone who has a pheochromocytoma can
33:29actually present with severe hypertension,
33:32flushing, sweating,
33:33heart palpitations.
33:35The majority of these tumors are benign,
33:39but they some of them can be malignant,
33:42particularly for some of these
33:46hereditary predispositions.
33:47So it's something that that's
33:49why if some you know a patient
33:51presents with a sudden neck, neck,
33:53mass or a mass mass in the abdomen,
33:56or is complaining of episodes of sweating,
34:00fatigue, anxiety, that makes me not fatigue,
34:03anxiety, heart palpitations,
34:04it's you know it might.
34:07It's it's, it's something.
34:08Something to think about, you know,
34:10maybe a referral to endocrinology.
34:12Not saying that everyone that presents
34:13with that will have these tumors,
34:15'cause they're very rare, but.
34:17They are something that we do.
34:20We do screen form.
34:21We do see patients with these tumors
34:23because there is also screening.
34:25For individuals who have a
34:27hereditary predisposition.
34:30Another, more rare hereditary predisposition
34:34is hereditary hyperparathyroidism,
34:36and I think when people think of
34:39hyperparathyroidism, they may not
34:40initially think of hereditary cancer.
34:42'cause hyperparathyroidism is not
34:44a cancer diagnosis, of course,
34:47is just an overactive parathyroid gland,
34:50but hereditary hyperparathyroidism can
34:53be related to other risks of humors,
34:57so the most common form of
34:59hereditary hyperparathyroidism.
35:01Is multiple endocrine neoplasia type
35:04one or M1 where the individuals with
35:07this with me and one will develop
35:11hyperparathyroidism over 90% of
35:13the time by the time they are 50,
35:16usually when they're in their 20s or 30s
35:18and they are at risk of other endocrine
35:21tumors of of the endocrine system,
35:24such as neuroendocrine tumors of the
35:26pancreas of the stomach of carcinoid.
35:29So it is important.
35:31When someone has particularly early onset
35:34hyperparathyroidism to actually evaluate,
35:37to evaluate if they have possibly
35:40have me in one and possibly some of
35:43these less common forms of fresh
35:46or hyperparathyroidism because it
35:48possibly could mean they might be
35:51at risk of other endocrine tumors.
35:53So those are just two examples,
35:55but just some of the other
35:57indications that you know maybe may
35:58not immediately come to mind when
36:00we think about hereditary cancer.
36:02Some of the more rare indications anyone
36:06with with medullary thyroid cancer,
36:08adrenocortical carcinoma,
36:09paraganglioma, pheochromocytoma,
36:11or red no blastoma at any age warrants
36:16a referral or anyone that has a close
36:19relative with any of these cancers.
36:22Anyone with any again rare or
36:24unusual tumors or physical findings
36:26so there are specific skin findings
36:29that even if they're benign,
36:31they actually can be indicative
36:33of a hereditary cancer syndrome,
36:35such as sebaceous carcinoma or
36:37sebaceous adenomas which we can see
36:39with Lynch syndrome or tricholoma
36:41which we can see with Cowden syndrome,
36:44which is related to the.
36:46The P10 gene. Melanoma is is common.
36:51The biggest risk factor for
36:53Melanoma or any skin cancer is of
36:55course fair skin and sun exposure.
36:58But if someone's had multiple
37:00melanomas usually over over 3,
37:03specially if they're at a younger age,
37:05that would warrant a referral
37:08to cancer genetics to rule out
37:11a hereditary Melanoma syndrome.
37:13Leukemia in children is unfortunately common,
37:16but if there are other rare
37:18childhood tumors that might,
37:20that would be an indication for
37:21a cancer genetics referral,
37:23such as again, a Renault blastoma.
37:27Sarcoma and osteosarcoma.
37:28Some tumors that are diagnosed in
37:32children can be indicative of a
37:35rare hereditary cancer syndrome.
37:38And anyone diagnosed with primary
37:40hyperparathyroidism before the age
37:42of 50 warrants a referral again,
37:44since the most common type of
37:48hyperparathyroidism, me and one.
37:51I'm hypercalcemia,
37:53which often is the first presenting sign
37:55that someone has hyperparathyroidism
37:57because elevated parathyroid hormone
37:59causes an elevation of serum calcium.
38:03The almost all people with me and
38:05one will have hypercalcemia by
38:07the time they're 50,
38:08so if someone has hyperparathyroidism
38:10before they're 50,
38:11that could indicate that you
38:14know it is important to rule
38:17out another previous position.
38:19And I say this for the end because it is
38:21not a rare indication,
38:22but anyone that has a fame
38:24reports a family history,
38:25but no mutation in any cancer gene
38:30Jersey one MLH one pal B2 ATM.
38:33Any cancer gene you know in a cousin,
38:37even in a first cousin once removed,
38:39if someone is reporting that that is
38:42a definite indication for genetic
38:44testing and it is very important if
38:46a patient is reporting that to you.
38:48That you do encourage them to get a
38:50copy of their relatives test results,
38:52because that can actually be really
38:55helpful in their own testing and
38:57actually ensuring their tests.
38:59Their own testing is accurate.
39:03So let's talk about out of pocket
39:06genetic casting options and
39:07direct to consumer testing.
39:09So out of pocket genetic testing options.
39:11Luckily in the last few years the
39:13cost of genetic testing has gone down
39:16significantly in the last several years,
39:18so years, years and years ago,
39:20over ten years ago,
39:21testing may have been a few $1000
39:24even just for BRCA one and two.
39:26Testing now because the technology is faster,
39:30it's better. It's cheaper now.
39:33Genetic testing can be performed
39:35through a large panel of genes.
39:38Again, all the genes that we've talked about.
39:40For an out of pocket costs of $250,
39:42there are a few commercial
39:44labs that are offering this,
39:46which has been really excellent because
39:48it doesn't prove access to genetic testing
39:52for patients without insurance coverage.
39:54For those patients who are
39:56motivated to pursue genetic testing,
39:58even if we don't seal are risk
40:00factors in their family.
40:01For a hereditary cancer syndrome
40:04and just one example here in vitae,
40:06they do actually have their own
40:08self pay option.
40:09Where to be $250 for diagnostic
40:13testing and this testing is different
40:17than the direct to consumer testing
40:21like 23 and me or ancestry.com
40:23which this test again detained
40:25other other labs is testing is a
40:29clinical diagnostic test but other
40:31direct to consumer testing like 23
40:33and me and ancestry.com is well how
40:36I've heard it described.
40:38It is like cocktail genetics.
40:39It's it's something fun.
40:41It's, you know, an ancestry.
40:43There's nothing indicating that the
40:45ancestry is actually is inaccurate.
40:47If anything actually appears
40:48to be quite quite accurate,
40:50but it's not something that should
40:53be used for clinical decision making.
40:56So just something to.
40:58To think about so.
41:01As a as an example,
41:04you know,
41:04let's say Diana is a 36 year old female.
41:07She's in good health.
41:08She comes in for an annual exam.
41:10She has Spanish ancestry.
41:12She's reports her mom had breast
41:15cancer 44 and passed away,
41:17but no other family history of cancer.
41:19And then Diana reports that she sent
41:22in a sample for genetic testing at
41:2423 and me and that her results were
41:27negative for BRCA one and BRCA 2.
41:29So the question I have and I was going to do.
41:32Cool,
41:33but it wasn't working out so
41:35I'm just going to.
41:37Close the question for
41:38you to think about and you
41:40can answer out loud where
41:42you are or in your head.
41:44Are Diane is genetic tests isn't informative.
41:48And does she need to be retested
41:50for BRCA one and BRCA 2 if
41:52her testing is negative?
41:53And let's say we actually have the report.
41:55Is confirmed does she need to be retested?
41:58Is this informative?
42:02And the answer is no,
42:06and and no so. So so 23andMe?
42:10Uhm, it's not to say so.
42:13Essentially what is important to
42:15know is that 23 NI they do offer
42:20testing for BRCA one and BRCA 2.
42:23But only selected variants
42:26you might remember.
42:28I said that earlier in the earlier in
42:31the talk I said that there are three
42:33specific mutations that are seen commonly
42:36in people that are Ashkenazi Jewish.
42:38Those are the three variants that.
42:41Are being tested for, so for Diana
42:44she may not have those variants and.
42:47A manned, but she also has Spanish ancestry,
42:51so she would not have been expected
42:53to have those variants at all,
42:55and 23 me does not do full gene
42:57sequencing of beers they wanted to.
42:59Does not do deletion duplication,
43:02and those three mutations are seen
43:04almost exclusively in people or
43:07Ashkenazi Jewish make up only three
43:09of 1000 known pathogenic mutations.
43:11So for Diana this is a very uninformative
43:14test and she would be recommended to have.
43:17Formal BRC wanted two testing gene
43:21sequencing and deletion duplication.
43:23And that's essentially what
43:24direct to consumer testing does.
43:26It looks at specific variants,
43:28and some of these variants may have a
43:30very small effect on health and may have
43:33a very questionable effect on health,
43:35and it's not.
43:35It's not very clear some for
43:37some of these variants,
43:39for even other diseases,
43:41how much risk is actually giving,
43:44and if something is not clear exactly how
43:46little of the gene that actually looking
43:48at so direct to consumer testing is,
43:50you know it is something that the the people.
43:53Lou,
43:54but it's something that should not be
43:56used for any clinical determination.
43:59What's what some people have been
44:01doing is that they can take the raw
44:03data from 23 and me and actually
44:06upload it to programs like one called
44:09promethease that actually builds a
44:11personal DNA report by looking at the
44:15genotype so they actually they actually
44:18can do that at not a large cost,
44:21but the problem with that is actually
44:23uploading these raw data files.
44:25There's actually a high false positive rate.
44:29Because just in terms of of how the
44:31data is uploaded and how the programs
44:34are there is it can actually report
44:36a pathogenic mutation that if we
44:39look test the patient clinically
44:41limitation is not there.
44:44So this is so this is is 11
44:48figure from from this test which
44:51actually showed that out of.
44:53Out of the the number of patients that
44:55report that had pathogenic variant
44:58detected by uploading the raw data,
45:0140% were a false positive and you can
45:03see most of those were in jeans that
45:06we often know about PRC two BRCA,
45:08one ATM MLH one related to Lynch syndrome.
45:12Check two TB 53 so genes that if
45:16someone had a mutation those genes
45:19that has clinical significance so
45:21individuals if they aren't aware of.
45:24The risk of false positives.
45:26They may be doing screening or
45:29preventative surgeries that may
45:30not be indicated so,
45:32particularly with things like raw
45:34data and direct to consumer testing.
45:36If there is a family history
45:37and a patient is concerned,
45:39the best thing they can do is meet
45:41with a genetic counselor and have a
45:44clinical test for hereditary cancer.
45:46And there are position statements
45:48from the National Society of Genetic
45:50Counselors about at home testing and
45:53things to consider and the American
45:55College of Obese and Gynecologists
45:57also have a position statement.
46:00Actually say quite nicely in their
46:02title that it creates confusion,
46:04so direct to consumer testing.
46:06Again for ancestry.
46:07For small things like that
46:09is something that again,
46:11cocktail genetic something that's fun.
46:13But for things like BRCA one and
46:15two testing or anything else,
46:16it's clinically indicated.
46:18Definitely a clinical diagnostic
46:21test is warranted,
46:22particularly if there's a family history.
46:26So let's talk about,
46:28you know genetic testing and
46:29kind of what would we talk about
46:32with with patients so.
46:33When we do genetic testing,
46:34there are three possible results we
46:36can get from a task which will one
46:39will stay positive means there is
46:41a pathogenic mutation detected in
46:43one of the genes analyzed and that
46:46there are associated cancer risks.
46:48Negative straightforward means
46:49that when the genes are analyzed,
46:52there's no known pathogenic mutations.
46:54The jeans look normal,
46:56there's no detectable hereditary cancer risk.
46:58And then there's the variant
47:01of uncertain significance,
47:02which is a variation in a gene.
47:05That the laboratory has not yet
47:08classified to pathogenic meaning it's
47:11causing cancer risk or benign variation,
47:14meaning it's just a polymorphism
47:17that's actually not impacting the gene.
47:20And variants of uncertain significance.
47:23They are very.
47:24They're quite common,
47:25especially when we do larger testing,
47:28which we do nowadays.
47:29We actually find variants of
47:31uncertain significance.
47:3220 to 30% of the time.
47:34This is an example report,
47:37and particularly it's always hard
47:39when you get a variant of uncertain
47:41significance in a gene like BRCA 2,
47:44but most of these variants are
47:47reclassified by the laboratory 2 benign.
47:50Two normal changes.
47:52That's why on the previous slide,
47:55if a varying divine stern
47:57significance is detected,
47:58medical management is not
48:00based on that variant.
48:02It's based only on personal
48:04family history factors.
48:05We have seen cases where someone
48:08is followed as if they have a
48:11real mutation in BRCA 1, BRCA 2,
48:14another gene that's actually a
48:16variant of uncertain significance
48:18and they're screened. They they may.
48:21They may have preventive surgery and
48:22then they find out in the future.
48:24It is actually a benign variation so
48:26we always go back to family history
48:28to guide management is something
48:30we kind of say innocent till proven
48:32guilty because most of the time the
48:35laboratory will update us with the
48:37report when they can get enough
48:39information to change their classification.
48:41Uhm,
48:42no,
48:42and actually I already talked about this,
48:44so I I've already.
48:46I'm I'm when someone step ahead.
48:48So really we also I want to mention
48:51point out we don't test relatives for
48:54variants of uncertain significance,
48:56only if it might be helpful in
48:59reclassifying that variant,
49:01meaning that sometimes it can be
49:02helpful to know did the variant come
49:05from your momma from your dad because
49:07your dad had pancreatic cancer and
49:09your mom is 85 and still living so.
49:12If the speakers say two variant
49:13came from your mom,
49:15I we might be less suspicious,
49:16but it came from your dad that maybe
49:19could maybe could add evidence or at
49:21least keep it at the level that it is.
49:23So that's why we only really test relatives.
49:26If it might be helpful,
49:27and reclassifying the the variant.
49:30And and this this can be hard for patients.
49:33It can be hard to have that uncertainty of.
49:36Is this something I'm gonna
49:38have to think about?
49:39It is something that is actually going
49:41to we find out that I'm as positive in
49:43the future and it can be hard to how
49:46to communicate this to family members.
49:48It's you know,
49:49it's something members can
49:50won't understand it.
49:51They might want to be tested for it.
49:53So this can be particularly tricky in
49:55communicating this with with patients,
49:57which is why we do take time
50:00before and after.
50:01Even before someone has testing to
50:02prep them and let them know this
50:04isn't this as a possible result,
50:06we can find that is quite common.
50:10And testing options are, they're all.
50:13They're all a little bit different.
50:14We do single site testing.
50:16If there's a known mutation in the family
50:18and no other suspicious cancer history,
50:21meaning that there's a mutation.
50:24We've confirmed with their report,
50:25there's nothing else.
50:26In those cases we would test
50:29for just that single mutation.
50:31Other options for those families
50:32where there's not a no mutation
50:35is a cancer site specific panel
50:37meaning related to genes.
50:39Only.
50:40Genes that are only related to
50:41the cancer is seen in the family,
50:43meaning that maybe if there's just
50:45breast or varying cancer in the family,
50:47limiting it to jeans that have a
50:50known association with hereditary
50:51breast or ovarian cancer.
50:53Well, this colon cancer in the family,
50:55keeping it only to hereditary colon cancer,
50:58expanded panels.
50:59We've been doing more often, meaning that.
51:01You look at multiple genes related
51:03to several types of cancer,
51:05including cancers.
51:06We may not even be seeing in
51:08someone's family.
51:09Such as colon cancer,
51:11Melanoma, uterine cancer,
51:12stomach cancer.
51:13So essentially all the more common horizon
51:16right cancer types we often can do that and
51:19will be called an expanded panel testing.
51:22But panel testing there are considerations
51:24because the more genes we look at,
51:26the higher chance we'll find something
51:28in a hereditary cancer gene,
51:30which could be expected
51:32or possibly unexpected.
51:33Some patients don't want to
51:35find an unexpected result,
51:37as I mentioned earlier,
51:38there are some genes that are
51:40included in testing nowadays,
51:41particularly panel testing that
51:43are have not been studied as long
51:46they have an unknown cancer risk,
51:48so there may not actually be
51:51screening recommendations 'cause for
51:52syndrome. Like Lynch syndrome
51:54and mutations in BRCA,
51:56one of your C2 there are very
51:59clear screen recommendations
52:00with some of these newer genes.
52:02We can find a mutation and still just
52:04follow someone based on personal or
52:06family history until we learn about
52:08what that gene is doing specifically.
52:11And as I mentioned earlier that
52:13when we do a larger panel probably
52:16more standard panel that we do,
52:17we find a VUS 20 to 30% of the
52:21time so that's that's quite a.
52:23A big chunk of the time we find at least one,
52:26and so some patients may not want the
52:29possibility of finding uncertain results,
52:31so something else to also think
52:33about when we offer genetic testing.
52:35Some of the benefits of genetic testing,
52:37you know it can end uncertainty.
52:39You know if there is cancer in the family,
52:41it can be helpful to know do is there
52:43a reason for why there's cancer in
52:45my family and do I have the reason
52:47for the cancer in the family?
52:49If I cancer risks for an individual,
52:51so then we know what screening we can.
52:53We need to be doing.
52:54It can also clarify cancer risks for
52:57relatives. If there is a positive result.
52:59We then know that other relatives
53:00would be at risk of inheriting
53:02that same mutation and then they
53:05can also have their own testing.
53:07And it can aid in medical decision making.
53:09Knowing again what screening
53:11they should be doing.
53:12Is it worth thinking about a
53:14prophylactic bilateral mastectomy and
53:16that can actually relieving anxiety?
53:18There are studies showing that even
53:20a positive result could actually
53:22be anxiety relieving,
53:23because some actually has the answer.
53:26They actually know why there's cancer
53:28in the family, what's causing it,
53:30and they know the specific
53:32risks instead of an unknown.
53:34There are some risks and
53:35limitations to genetic testing,
53:37such as a negative result
53:39may be uninformative,
53:40or it may be falsely reassuring.
53:43There are concerns about
53:45genetic discrimination,
53:46so there are laws in place that do
53:48make it illegal for most health
53:50insurance companies and most employers
53:53from discriminating against someone
53:54with a positive genetic test result,
53:57but these do not apply to things
54:00like life insurance,
54:01long term care or disability and it actually.
54:04Possibly could impact fitness
54:06for duty in the military,
54:08so it is something to think about
54:10when someone has genetic testing.
54:13You know what policies they have in place?
54:15Are they actively serving in the
54:17military just to just to think about?
54:19In timing of testing,
54:21might not be optimal depending
54:22on someone's current.
54:24Current lifestyle or current current
54:26plans and Shank testing is an option.
54:29Even though there are
54:30clinical recommendations,
54:31it is an option and for some
54:33patients they actually prefer not
54:34to know if they have hereditary
54:36risk of cancer and they may not
54:38wish to know future cancer risks.
54:39There are limitations in the testing,
54:42so it is possible even though are the
54:45testing technology has grown a lot,
54:47though there are sometimes undetectable
54:50mutations and current technology that
54:52could be missed in a known hereditary
54:54cancer gene testing technology will
54:56change and improve overtime just
54:58like it has in the last ten years.
55:00But that is a limitation and not all
55:03inherited cancer syndromes are known.
55:05So in the future kind of like I
55:08mentioned with BRCA one and BRCA 2.
55:10Four 2013 is out is outdated.
55:14Is possible I could be saying
55:16in you know 2030 if any test
55:19after 20 before 2033 is outdated.
55:21You know we are likely learn more about
55:24inherited cancer syndromes and new genes.
55:26So more testing may be needed in the future
55:29to help clarify risk for some families.
55:32And this is an example of.
55:34Uninformative genetic testing,
55:36where the probe and two were there.
55:39The circle there is pointing to
55:41she's had negative genetic testing,
55:43but has a very striking family history,
55:45so her testing is really not
55:47informative and it's not someone
55:49that you feel comfortable saying oh
55:51you are at average risk for cancer.
55:54We always go back to family history
55:56to This is why we go back to family
55:58history to guys screening until we
56:00can get informative relative tested
56:02and determine is is there a familial.
56:05Mutation,
56:06but maybe this probe and did not inherit.
56:09Which is why, again,
56:10it is very important for sometimes
56:12testing the affected relative first,
56:14and if that relative has had genetic
56:16testing it is really important for
56:18you to be talking to your patients
56:20and explaining it is important to
56:22get those medical records for us.
56:26Engineer counseling in the session,
56:27what would I do and will my colleagues do?
56:30It's really a combination of education,
56:33talking about the diagnosis
56:35of hereditary cancers,
56:36syndromes offering psychosocial support,
56:39advocating for our patients,
56:41talking about talking about risks.
56:43So it is really this.
56:45We're we're here for resource for,
56:47for patients were also here
56:49for resource for you.
56:50You know,
56:51in terms of in terms of risk
56:54assessments and patients going forward.
56:56The main I'll go through some of
56:58this this briefly 'cause I don't
57:00wanna go over too much overtime,
57:02but there is a lot.
57:05There's a lot in a genetic counseling
57:08session where we go through medical history.
57:11We take a detailed family history.
57:13We talked about the risk factors.
57:14We've seen, the family,
57:15we do, a risk assessment.
57:17We talk about specific genes or specific
57:19syndromes the patient may be at risk for.
57:22We talk about,
57:23you know the what hereditary cancer is,
57:26why we do testing.
57:28What screening would change
57:29if someone was positive?
57:31You know why are we doing
57:32this testing at all?
57:33We talk about different testing
57:35options in terms of limited
57:37panels or expanded panels.
57:39There's research.
57:39Of course we coordinate the testing we
57:42call the patients with their results,
57:44explain their results,
57:45and then of do any follow up in terms
57:48of referrals to specialists and also
57:50just be a resource for the patient.
57:52Transfer information,
57:53so for what you can do to help,
57:56have your patients prepare
57:57probably the most important thing
57:59is to encourage their patients
58:01to collect their family history.
58:02So if you place a referral
58:04for cancer genetics,
58:05the most helpful thing is for
58:07that patient to be talking to
58:09relatives getting that information,
58:11particularly if there's no mutation,
58:13it's very important for to have
58:15that confirmed with records.
58:16It actually can be impact the accuracy
58:19of the patient's own testing,
58:20which some patients may not understand.
58:23There can be differences in laboratories
58:25and detecting specific variants,
58:27so we cannot confirm what lab or
58:30what specific variant or relative
58:31had it's possible the patient
58:33could get an uninformative or
58:35even a false negative result,
58:37so anything any medical
58:39records from relatives,
58:40any information is very helpful.
58:45Which I just you know,
58:46bring those milk records visit to the visits.
58:49And. And again, encourage them to get
58:53copies of any any genetic test results.
58:57So after the referral, it takes about,
59:00UM, the initial jet counseling visit is
59:0360 minutes. They are sent a questionnaire.
59:06And the patient schedules an appointment.
59:08They do a very brief intake.
59:10Again, the initial genetic counseling
59:12visit takes about 60 minutes.
59:14We again go through that that whole
59:16session and the cases are reviewed.
59:18Our weekly cancer genetics and prevention
59:21program the just out of a meeting where
59:24we review all the cases altogether.
59:27Patients are disclosed.
59:28The results over the phone or in person.
59:30If the patient prefers and the
59:32patient does get a copy of their
59:35results and a detailed summary letter.
59:37So I guess I'll just end this by saying,
59:40uhm, you don't have to be the
59:43experts on her Ezra Cancer.
59:45We care for a resource for you.
59:47You're really, you know,
59:47the the front,
59:48the front line for these patients to really
59:50gauge their personal and family history.
59:52So I really just less last thing I'll say,
59:56and I think everyone for your attention
59:59and is a pleasure talking everyone.
01:00:01And I will take any questions.
01:00:07Hi Amy, thanks for a great
01:00:09talk that was really you.
01:00:11You managed to pack in a lot there so
01:00:14thank you so much I do just want to
01:00:16let all of the attendees know that the
01:00:19session is being recorded and a link to
01:00:21the recording will be on our website.
01:00:24So if you wanna go back and listen
01:00:26to parts of Amy's talk you will
01:00:28have access to that in the future.
01:00:30We also have a number of resources on
01:00:33our website including fact sheets that
01:00:35you and your patients may find helpful so.
01:00:37And encourage everyone to
01:00:39look at their website.
01:00:40And I believe that, UM,
01:00:42the website will be included and
01:00:45post conference communications soum.
01:00:47We'd like to encourage people to enter
01:00:51some questions for Amy in the Q&A and Amy,
01:00:54we do have a couple here,
01:00:56and so the first one,
01:00:58the first question we have,
01:01:00is whether Gardner's syndrome
01:01:02is something separate or whether
01:01:05that actually is attenuated.
01:01:08Uhm Polly process.
01:01:10Great, great question.
01:01:12So Gardner syndrome is I would
01:01:14say it's an outdated syndrome.
01:01:17It was mainly used to describe
01:01:20if someone had specific.
01:01:23Less common features that we
01:01:26would see with classic faps,
01:01:28but we know now that people
01:01:30with Gardner syndrome do have
01:01:32pathogenic mutations in a PC,
01:01:35so we really just prefer to
01:01:38call it faps or attenuated faps.
01:01:41So it's not so I would say
01:01:43the answer to your question.
01:01:45They they are the same.
01:01:47They just said Gardner syndrome was house,
01:01:50certain phenotypes were were described,
01:01:53particularly some of the less
01:01:55common features of of faps like
01:01:58extra teeth and things like
01:02:00that oftentimes was described
01:02:02with the four Gardner syndrome,
01:02:04but nowadays it is packaged together.
01:02:07But that is an important point
01:02:09that some people still use some
01:02:11of the older terminology.
01:02:12For Gardner syndrome.
01:02:13So if someone does report a family
01:02:16history of Gardner syndrome,
01:02:17even though that's may not be
01:02:19a term we use currently,
01:02:20that would also warrant a referral.
01:02:26And the next question we
01:02:28have is an interesting one.
01:02:30There's an attendee who's wondering
01:02:32if we think the ages at the time
01:02:36of diagnosis are getting younger
01:02:38in subsequent generations.
01:02:40So, for example,
01:02:41if someone's mother had breast
01:02:43cancer at 55 with a BRCA mutation,
01:02:47are we seeing her daughter
01:02:49who has a mutation having her
01:02:51breast cancer earlier in life?
01:02:54That is, that's a great question.
01:02:58As with with BRCA one and BRCA 2 this
01:03:02and we we often call this in genetics
01:03:06anticipation where the phenotype appears
01:03:08to present at a younger and younger age.
01:03:13There's no known evidence of
01:03:16anticipation in BRCA one and BRCA 2.
01:03:20It's it's it's. It's hard to say,
01:03:22but there can be what we
01:03:24call variable expressivity,
01:03:25meaning that someone could have
01:03:27the same mutation and beers
01:03:28they want to be receipt to,
01:03:30but they will not always develop
01:03:32breast cancer at the same
01:03:34age or even develop breast.
01:03:36You know someone made available
01:03:37varying cancer or or breast cancer,
01:03:39which we call variable expressivity.
01:03:41So that might explain why in some
01:03:43families it does appear that Amma,
01:03:45a mother may have breast cancer at a later
01:03:48age and her daughter has breast cancer and.
01:03:50Earlier age,
01:03:51not because of something like anticipation,
01:03:54but possibly do that variable expressivity.
01:03:57Although I do,
01:03:58I do know that there was some older data.
01:04:00I think Claire you mentioned this
01:04:02to me a few years ago where there
01:04:05is some data suggesting maybe
01:04:06anticipation with Lee from Mini
01:04:08syndrome where individuals actually
01:04:10appear to develop Lee from many
01:04:12syndrome associated cancers,
01:04:14particularly breast cancer at younger
01:04:17age and subsequent generations I.
01:04:20In terms of additional research on that,
01:04:22I have not seen anything recent about that,
01:04:25but I know there was some hypothesis
01:04:28that leaf armenie syndrome may
01:04:30have some level of anticipation.
01:04:32But in terms of other hereditary
01:04:34breast cancer syndromes,
01:04:34there's none that we know of yet.
01:04:40Yeah, and I would just add that even
01:04:42with these hereditary cancer syndromes,
01:04:44the mutation is not the only
01:04:46contributing factor to cancer risk.
01:04:48Lifestyle environment.
01:04:49All of those things still play
01:04:51a role in cancer development,
01:04:54and so it's possible that some
01:04:56of those earlier cancer diagnosis
01:04:58that you're you're mentioning
01:04:59are related to other factors
01:05:02outside of the genetic mutation,
01:05:04or in addition to the genetic mutation.
01:05:07And I think we still have a
01:05:09lot to learn about hereditary.
01:05:10Cancer genetics we've come a long way.
01:05:12We know a lot and they will learn
01:05:14more and perhaps some of these
01:05:16hereditary cancer syndromes do,
01:05:18in fact have anticipation.
01:05:19And we just don't know yet.
01:05:25Those are all the questions
01:05:26that were entered into the Q&A,
01:05:28so I don't know if any of our
01:05:30panelists have any questions or if
01:05:32we want to give people just a minute
01:05:35in case any other questions come up.
01:05:40Maybe while waiting I'll post a
01:05:42question Amy that was a great talk.
01:05:45So quick question.
01:05:46You just you went over very nicely
01:05:48about what happened with Brad.
01:05:50Can white people got retested
01:05:52then and then towards the end?
01:05:54You also discuss a little bit
01:05:55more that there may be some.
01:05:56Uh, in the future,
01:05:59opportunities for bettering the
01:06:00testing and actually being able to
01:06:02detect a few more number 4 so when
01:06:05do you think people will will have
01:06:07to consider re sending the patient?
01:06:10Who previously had tested negative.
01:06:12I'm talking in general terms.
01:06:13What do you think would be a general
01:06:16recommendation that we could follow
01:06:18in terms of in terms of that?
01:06:20That's a, that's a.
01:06:22That's a great question,
01:06:23and it's something that patients also ask me.
01:06:25Even now they they say, well,
01:06:27when should I call you?
01:06:28You know, for more testing, I think it's.
01:06:31It's hard now that testing has gone so
01:06:34comprehensive, I would say so quickly.
01:06:37Even the last five years.
01:06:38What I've been saying.
01:06:39What I was saying to patients,
01:06:41and this is,
01:06:42but again,
01:06:43this is not something that's
01:06:44really hard and fast rule.
01:06:46I would say at least five
01:06:48years to check back,
01:06:50unless there was a change in someone's
01:06:53family history like a new cancer diagnosis,
01:06:55that possibly could mean that other
01:06:57genes related to that diagnosis
01:06:59were not included in the testing.
01:07:01But if there's no changes.
01:07:03Someone's personal or family history.
01:07:05I would say every five years
01:07:08is a good place to check,
01:07:09and it's possible even in
01:07:11five years from now.
01:07:12Maybe it's it might not change as much,
01:07:16but I can't imagine the testing jumping
01:07:19to such a huge amount of clinical
01:07:22significance in less than five years.
01:07:25I don't know Clearview any other
01:07:27thoughts on that in particular?
01:07:30No, I agree. I mean,
01:07:31I think the testing technology doesn't.
01:07:33It changes quickly,
01:07:34but not that quickly.
01:07:36So five years is probably a good.
01:07:39An estimate, but I would also just reiterate
01:07:41one other thing that you said there.
01:07:43If the personal or family history changes,
01:07:46that's another really important
01:07:47touch point for patients to
01:07:49get back in contact with us,
01:07:51because that could certainly change things,
01:07:55so those are good time point
01:07:57to consider re evaluation.
01:08:02Right, I think that's it for question.
01:08:05So Amy, thanks again for your talk
01:08:07and we hope that everyone will
01:08:09join us next week for the second
01:08:12half of this seminar series.
01:08:16Thank you everyone. Have a good night.