Identifying and Caring for Individuals with High Risk & Inherited Cancer Syndromes
October 29, 2021Information
Genetics CME | October 28, 2021
Implementing Screening and Prevention Strategies for Individuals Identified to be at Increased Risk for Cancer
Presentations by:
Melanie Lynch, MD | Elena Ratner, MD | Xavier Llor, MD, PhD | James Farrell, MBChB
ID7095
To CiteDCA Citation Guide
- 00:00So I think we'll get started.
- 00:02My name is Claire Healy.
- 00:04I'm one of the genetic counseling
- 00:05managers and the smilow cancer
- 00:07genetics and prevention program.
- 00:09So, on behalf of the program,
- 00:11I'll welcome you all to The Tonight.
- 00:13Two of our seminar series,
- 00:16the title of tonight's seminar is
- 00:18implementing screening and prevention
- 00:20strategies for individuals identified
- 00:22to be at high risk for cancer.
- 00:24And a few housekeeping things
- 00:26before we get started.
- 00:28Please try and keep yourself muted and
- 00:30remain muted during all of the talks.
- 00:33We've saved time at the end of all
- 00:35of our lectures for questions,
- 00:37but feel free as we go through these
- 00:39lectures to enter questions into the Q&A.
- 00:42And tonight we're going to
- 00:43start with our first speaker,
- 00:45doctor Melanie Lynch.
- 00:46Doctor Lynch is director of breast
- 00:49surgery at the Smilow Cancer
- 00:51Hospital locations in Bridgeport,
- 00:52Fairfield and Trumbull,
- 00:53and the Norma from Breast Center.
- 00:56She's a board certified general
- 00:58surgeon and fellowship trained
- 00:59surgical oncologist and Doctor Lynch.
- 01:01Thank you for joining us.
- 01:03Thank you, thank you for
- 01:05the kind introduction and
- 01:06for letting me join tonight.
- 01:08I'm gonna share my screen.
- 01:14How's that work? Yep.
- 01:19There we go. How's that look?
- 01:21Perfect OK. So when we started
- 01:25discussion of breast cancer risk,
- 01:27we certainly have to talk about
- 01:28breast cancer incidence and looking
- 01:30at breast cancer incidence and how
- 01:32this has changed over the years.
- 01:34You can see how with increasing
- 01:37screening mammography or breast
- 01:38cancer incidents did go up.
- 01:40Our mortality though has
- 01:42continued to go down,
- 01:43and that's because most of the cancers
- 01:45that were identifying now in the
- 01:47earlier stages when they are curable.
- 01:49You'll notice in this timeline you
- 01:51see this peak here in the 1980s.
- 01:53This is when screening.
- 01:55Went up dramatically when our first
- 01:57lady was diagnosed with breast cancer.
- 01:59The other thing you're going to
- 02:00notice here is this dramatic dropoff
- 02:02and breast cancer incidents that
- 02:03happened in the early 2000s with
- 02:05the publication of the Women's
- 02:07Health Initiative trial that
- 02:08demonstrated a link between hormone
- 02:10replacement therapy at the time of
- 02:12menopause and breast cancer risk.
- 02:16When we think about what
- 02:18effects breast cancer risk,
- 02:19we know that there are a number
- 02:21of factors that we can control
- 02:22and there are a number of factors
- 02:24that are out of our control.
- 02:26We know that we can decrease
- 02:28risk by maintaining a healthy
- 02:30weight by exercising regularly.
- 02:33And by limiting the amount of
- 02:35alcohol that we drink per week,
- 02:37we also know that there's some
- 02:38things that we can't control,
- 02:40including exposure to ionizing
- 02:42radiation for treatment for cancer.
- 02:44When, especially at a young age,
- 02:46a family history of cancer,
- 02:48or an inherited genetic
- 02:51susceptibility to cancer.
- 02:53When we look at breast cancer
- 02:55and these risk factors,
- 02:57the risk is variable.
- 02:58We know that breast cancer risk is
- 03:00very closely related to age that women
- 03:02who are 70 years old or 10 times as
- 03:05likely to be diagnosed with breast
- 03:07cancer is someone in their 30s.
- 03:09We know that family history has a
- 03:11significant role in breast cancer risk,
- 03:13and it really depends on the
- 03:15number of affected relatives.
- 03:16Breast density also increases
- 03:18breast cancer risk.
- 03:19We're going to look at that in
- 03:20a minute hormone replacement
- 03:22therapy as we talked about.
- 03:24Therapeutic radiation obesity has a
- 03:26very significant role in breast cancer
- 03:29risk and asked us regular alcohol use.
- 03:33I get many questions about breast
- 03:34density and breast cancer risk,
- 03:36and here's an example of what
- 03:38breast density looks like.
- 03:40This level one is an entirely
- 03:43fat replaced breast,
- 03:44which is more easily screened and
- 03:46is associated with a lower risk
- 03:48of breast cancer as opposed to an
- 03:50extremely dense breast which lowers
- 03:52the sensitivity of mammography
- 03:53but is also associated with an
- 03:55increased risk for breast cancer.
- 03:59When we think about breast cancer and
- 04:02inherited risk related to family history,
- 04:04we know that if we look at the total
- 04:06number of breast cancer cases 70 to 80%
- 04:09of them are unrelated to family history.
- 04:11Where a family history is
- 04:13associated with up to 20% of cases,
- 04:15and of those cases we know hereditary breast
- 04:19cancers make up five to 10% of the total.
- 04:25So how do we estimate
- 04:26individual breast cancer risk?
- 04:28There are a number of statistical models.
- 04:31And I think we're probably all
- 04:33familiar of heard the quote that
- 04:36all statistical models are wrong,
- 04:38but some are useful.
- 04:39And here's one that is particularly useful.
- 04:42This is called the Tyra Kuzyk model
- 04:45that takes into account some of
- 04:47the things we just talked about.
- 04:49Age agent men are key, height and weight.
- 04:53Childbirth, previous biopsies
- 04:55and their results,
- 04:57breast density and family history.
- 05:00We can enter these into this model
- 05:03and then calculated breast cancer
- 05:05risk for individual patients.
- 05:08We have guidelines for management
- 05:10patients who are considered at increased
- 05:12risk for breast cancer and that has
- 05:15been defined by expert opinion at a
- 05:17lifetime risk of greater than 20%
- 05:19for women who fall into this group,
- 05:21we might consider advanced screening,
- 05:25which would include both
- 05:27mammogram and breast MRI.
- 05:29We use elements from the family history
- 05:31and the patient's personal history
- 05:33to decide the age to begin screening
- 05:35and most guidelines suggest that
- 05:37we stop screening within 10 years.
- 05:39At the end of life.
- 05:41I just wanted to share this
- 05:44picture of a screening breast MRI
- 05:46from a recent patient of mine.
- 05:48This was a patient who in her mid
- 05:5130s was diagnosed with pancreatic
- 05:52cancer and treated successfully
- 05:54and was a long term survivor.
- 05:57She had been undergoing routine
- 05:59screening when her endocrinologist
- 06:01suggest that she get genetic
- 06:02testing and she was found to have
- 06:04a mutation in the BRCA gene.
- 06:06She came to see me and we got
- 06:08a breast MRI for screening and
- 06:10despite having a very normal.
- 06:11Looking mammogram,
- 06:12she had this area on her of
- 06:16enhancement on her breast MRI
- 06:18that was in occult breast cancer
- 06:21and so this is an example of how
- 06:24screening MRI adds to our ability
- 06:26to screen high risk patients.
- 06:30So my professional society,
- 06:32which is the American Society of
- 06:34Breast Surgeons, along with the
- 06:37American College of Radiologists,
- 06:38have now moved towards a
- 06:40model of recommending risk
- 06:42based breast cancer screening,
- 06:44which includes a risk assessment for
- 06:46all women at by the age of 30 to
- 06:50determine if you're at average risk
- 06:52or higher than average risk and how
- 06:55women should be screened based on
- 06:57their individual risk assessment.
- 06:58It's a move from.
- 07:00Age based screening to risk based screening.
- 07:03And at women who are higher
- 07:05than average risk,
- 07:06who recommend starting with
- 07:08a mammogram and breast MRI,
- 07:11the MRI can start at a younger
- 07:14age at 25 if needed.
- 07:16If the family history suggests that,
- 07:17or if there's a genetic
- 07:20syndrome that suggests that.
- 07:22And also that women with a prior
- 07:23history of breast cancer at a young
- 07:25age and with non dense breasts versus
- 07:27dense breasts that we might add
- 07:29MRI for women with dense breasts.
- 07:34So we know that genetics plays a
- 07:37role in breast cancer risk and that
- 07:40of those cases where genetics where
- 07:43there's a mutation in a breast
- 07:45cancer gene that the majority of the
- 07:47mutations that we identify associated
- 07:48with breast cancer are two genes,
- 07:50BRCA, one and two.
- 07:52Although there were several other
- 07:55genetic syndromes associated
- 07:56with increase breast cancer risk.
- 07:59When we look at those genes,
- 08:01we and make a plan for both screening
- 08:04and prevention for patients with genetic
- 08:07syndromes we consider how penetrant gene is.
- 08:11How likely is a patient to develop
- 08:13cancer if they have a mutation in that
- 08:16gene and so for the very high penetrance.
- 08:19Genes where there's a very
- 08:21high risk of cancer,
- 08:22we find those to be less common and
- 08:25those genes include BRCA one and two,
- 08:27which are more commonly known.
- 08:30Other genetic syndromes,
- 08:32including P53 and P-10.
- 08:34The modern,
- 08:35the moderate penetrance genes ATM palb
- 08:382 and check two have a lower risk of
- 08:41breast cancer associated with them,
- 08:43but they're much more common in the
- 08:46population and I just saw a very busy
- 08:48clinic today and I saw examples of
- 08:51patients with all three of those.
- 08:53Mutations.
- 08:57So when we talk about breast cancer
- 09:00prevention, we can identify a group
- 09:02of women where we might consider
- 09:04treatment to help reduce their
- 09:07lifetime risk of breast cancer.
- 09:09The chemo prevention criteria that are
- 09:12commonly accepted include women who
- 09:14are older than age 35 who have a life
- 09:17expectancy of at least ten years and
- 09:20have one of these high risk factors.
- 09:22We talked about thoracic radiation
- 09:25for treatment, especially if you're.
- 09:27Young, A history of lobular carcinoma
- 09:30Insight 2A predicted five year cancer risk.
- 09:33We looked at one model called the GAIL model.
- 09:35There are called the tire acoustic
- 09:38model earlier.
- 09:38There's also the GAIL model,
- 09:40which is predictive of five year
- 09:42cancer risk or any woman who
- 09:44has a biopsy that shows atypical
- 09:46cells or atypical hyperplasia.
- 09:51As we start to talk about prevention,
- 09:53I just wanted to clarify
- 09:54a couple definitions.
- 09:55The first one is Chemoprevention,
- 09:57which is the use of drugs,
- 09:59vitamins or other agents to reduce
- 10:01cancer risk and to delay the
- 10:04development or recurrence of cancer.
- 10:06We have two medications that
- 10:08we types of medications we
- 10:10currently use for chemoprevention.
- 10:12The first is selective
- 10:13estrogen response modifiers.
- 10:15This is a drug you might have heard
- 10:17of called tamoxifen or Raloxifene.
- 10:19These block estrogen at its receptor.
- 10:22The other class of drugs we
- 10:24might use or called the aromat
- 10:26ACE inhibitors and these reduce
- 10:28estrogen levels in the body.
- 10:30For women who are post menopausal by
- 10:33blocking an enzyme called aromat ace,
- 10:36this is a quick diagram that just
- 10:38shows the difference of tamoxifen
- 10:41would block the binding of estrogens
- 10:43to the receptor on the cells.
- 10:46The Aromat ace inhibitors block
- 10:48the production of estrogens by the
- 10:51peripheral fat cells in the body.
- 10:53Which is the primary source
- 10:55of estrogen after menopause?
- 10:59So there's been several
- 11:00studies that have been done.
- 11:01Looking at these medications
- 11:03for breast cancer prevention,
- 11:05these have been summarized
- 11:06in a meta analysis by EU.
- 11:09S. Public Health task force.
- 11:11It's kind of a busy slide,
- 11:13but you can see over here in
- 11:15this column that when you
- 11:17take these studies altogether,
- 11:19they basically favors treatment,
- 11:21showing that these medications are
- 11:24effective in reducing breast cancer risk.
- 11:30And there's a recent trial that we're all
- 11:33very excited about that looked at low dose
- 11:37tamoxifen for prevention of breast cancer.
- 11:40So many women who are increased risk for
- 11:43cancer where we recommend medical therapy
- 11:45will often have symptoms or side effects
- 11:48related to therapy that limits its use.
- 11:51The dose of tamoxifen that we use
- 11:53for treatment of cancer patients and
- 11:54that was used in the initial trials
- 11:57with 20 milligrams a day.
- 11:58The newest trial looked at a dose.
- 12:00Of five milligrams a day,
- 12:02and would that lower dose still be
- 12:05effective for cancer prevention?
- 12:07It was a randomized trial conducted at
- 12:10multiple sites that included 500 women
- 12:13who had a diagnosis of atypical abnormal
- 12:16cells on a biopsy or lobular carcinoma.
- 12:19Insight two,
- 12:19they were given 5 milligrams of
- 12:22tamoxifen a day for three years,
- 12:24or a placebo,
- 12:26and then they were followed for five years.
- 12:30Just a quick look at the data.
- 12:32If you look at the graphs here,
- 12:34these looked at the rates of breast cancer.
- 12:38Comparing the women who took placebo,
- 12:40which is the blue line to women
- 12:43who took tamoxifen,
- 12:44which is the red line and it showed that
- 12:48tamoxifen prevented about half of the
- 12:50episodes of breast cancer in these patients.
- 12:53Even better,
- 12:54if you look over here,
- 12:56it showed that of the adverse events
- 12:58that can be associated with tamoxifen,
- 13:01including a DVT or pulmonary
- 13:04embolism or uterine tumors that it
- 13:07appeared that this lower dose of
- 13:10tamoxifen was as safe as placebo.
- 13:12So this gives us a new effective
- 13:16tool for risk reduction.
- 13:18And of course,
- 13:19as a surgeon,
- 13:20I would need to talk about surgery
- 13:22for risk reduction.
- 13:23We only use this for patients with the
- 13:26BRCA one mutation who have the highest
- 13:29risk of breast cancer related to that
- 13:31previous graph that we looked at.
- 13:33So the studies that have looked at
- 13:36surgery for risk reduction have only
- 13:39looked at this very high risk population.
- 13:42And in the large studies that have
- 13:44been combined and looked at together,
- 13:46the risk reduction by performing a
- 13:50preventive mastectomy is greater than 95%,
- 13:52and we know that the there's also a
- 13:55mortality benefit for these patients
- 13:57that they live longer and do better.
- 14:01I just wanted to show a brief picture
- 14:02of a ****** sparing mastectomy
- 14:04'cause many patients have a lot
- 14:06of questions about this when we
- 14:08talk about this operation,
- 14:09and I thought that this picture from
- 14:12a picture from this publication was
- 14:14very useful to show that when we
- 14:17do this procedure we can spare the
- 14:20entire skin pocket and the ****** that
- 14:23we can do a reconstruction with a.
- 14:27Collagen matrix with an implant
- 14:28or we can do use the patient's
- 14:31own tissue to reconstruct.
- 14:33And get a very get a very good
- 14:36cosmetic result and also have a
- 14:38very safe result for patients.
- 14:42And that we can take this into
- 14:44different types of surgeries now,
- 14:45and we can really craft an operation
- 14:48to help meet every patient's needs.
- 14:50Sometimes they're staged operations.
- 14:53Sometimes we reduce the skin pocket or
- 14:55change the shape of the skin pocket,
- 14:56but can always come up with a reconstruction
- 14:59plan that works well for patients.
- 15:01And then I would be remiss if I
- 15:03didn't talk about primary prevention.
- 15:05I'm just at the end of my time,
- 15:07and so I'm just going to mention the
- 15:09importance of the plant based diet.
- 15:11We do have multiple studies that
- 15:13demonstrate that a diet that focuses
- 15:16on at least five servings of fruits
- 15:18and vegetables a day we know helps
- 15:21reduce future breast cancer risk.
- 15:23So with that I'm not going to go over my
- 15:26time and thank you for your attention.
- 15:36After lunch, thank you for such
- 15:38a nice talk to our attendees.
- 15:40Feel free to enter your questions
- 15:42for Doctor Lynch into the Q&A.
- 15:46I would like to now introduce Dr.
- 15:49Shabeel or Doctor Laura is a
- 15:51gastroenterologist and the
- 15:53director of the Smilow Cancer
- 15:55Genetics and Prevention program.
- 15:57He's also the director of the
- 15:59Colon colorectal Cancer Prevention
- 16:01program at Yale University and
- 16:03Smilow Cancer Hospital and associate
- 16:05director for cancer screening.
- 16:07Thank you for joining us.
- 16:08Doctor lore.
- 16:10Thank you very much Sir.
- 16:11It's a pleasure to be here today.
- 16:13Let me see we can share the screen.
- 16:19Can we see well?
- 16:23Alright, I have noticed those are
- 16:25set to make, so when we're thinking
- 16:29about the cancer predisposition
- 16:31and and genetic defects by now,
- 16:34we know that it is about over 100
- 16:38genes that have been discovered that
- 16:40they carry either high or moderate
- 16:43risk of cancer really defined as
- 16:45greater than two full relative
- 16:47risk of having any type of cancer.
- 16:50So a significant number of
- 16:52these genetic defects and they.
- 16:54Do affect many different organs,
- 16:57implying a higher risk of cancer
- 16:59when we look at the, uh,
- 17:02colorectal cancer specifically,
- 17:04and we look at the entire pile
- 17:08of colorectal cancers.
- 17:09But we'll see, is there.
- 17:12But is that about 5% or a little bit
- 17:15over 5% of all colorectal cancers will
- 17:18have an underlying high penetrance.
- 17:20Mutation germline mutation that would
- 17:22predispose to a higher risk of color.
- 17:25Colorectal cancer and about
- 17:28another 5% or so that would have
- 17:31moderate penetrance mutations.
- 17:32The ones that increase the risk
- 17:34but not to the level of the high
- 17:37penetrance mutations and if we
- 17:38look at the at this first group
- 17:40of high penetrance mutations,
- 17:42the more predominant ones are the
- 17:44ones that cost Lynch syndrome.
- 17:46The ones due to germline mutations
- 17:48in the mismatch repair genes.
- 17:50And then at the lower number,
- 17:52but also very important,
- 17:54the ones that do cost polyposis,
- 17:56particularly APC or bailing
- 17:58mutations in the MYH gene,
- 18:01we also find other mutations that
- 18:04are not as clearly well established
- 18:07as causing correct or increasing
- 18:09colorectal cancer risk,
- 18:11and among the moderate ones we do have,
- 18:14particularly a specific mutation in
- 18:18APC I 1307 K mutation, for instance.
- 18:21Check two mutations or monolithic myh
- 18:23mutations that again does increase the risk,
- 18:26but not to the level of the high
- 18:29risk or the high penetrance
- 18:31mutations that we see with lynching
- 18:34them for instance or or FP.
- 18:37And this is true for for the overall group
- 18:40of individuals with corrective cancer,
- 18:43and certainly is true for the
- 18:44individuals that are older than 50,
- 18:46which are the majority of this patient.
- 18:48So in general,
- 18:49but 10% will have these germline mutations.
- 18:52And 90% of them would not
- 18:54have these mutations.
- 18:56But if we look at younger individuals,
- 18:57for instance,
- 18:58individuals who are younger than 50
- 19:00who developed colorectal cancer,
- 19:02the proportion of individuals that
- 19:04will have a germline mutation related
- 19:08to cancer risk will be higher.
- 19:11That will go up to close to
- 19:1320% being 10% lynching.
- 19:14And if we look even at a lower age looking
- 19:18at individuals who are younger than 35,
- 19:21then here.
- 19:22We'll see that about 45% of those individuals
- 19:25will have a German language issue.
- 19:27That's why it's so important
- 19:29that as individuals are diagnosed
- 19:31at a younger and younger age,
- 19:33we really do genetic testing
- 19:35on these individuals,
- 19:36because there are chances of having a an
- 19:39inherited cancer syndrome will be much,
- 19:41much higher than individuals who
- 19:44develop those cancers at an older age.
- 19:47And we've looked at the representation
- 19:51among the colon cancers.
- 19:54Of these cases, but what is the true actual
- 19:57incidence among the general population?
- 20:00So for the most common colon cancer syndrome,
- 20:02which would be a lynching, dromas?
- 20:03We mentioned one in 279 individuals,
- 20:07not people with cancer,
- 20:09but any individuals will have a
- 20:11mutation in any one of these mismatch
- 20:14repair genes that cost Lynch syndrome.
- 20:17So that means that more than a million
- 20:19Americans do have leaned syndrome.
- 20:21Many of them have not been diagnosed yet.
- 20:24And there's.
- 20:24Plenty of work to be done in that scenario.
- 20:27On the other hand,
- 20:29important to point out that actually the
- 20:32mutations in the mismatch repair genes that
- 20:35cause in children that are more common
- 20:37which are cheeks in particularly PMS.
- 20:40So those are the ones that
- 20:43carry a lower penetrance,
- 20:45meaning they have they have a lower risk of
- 20:48cancer that complicates things a little bit.
- 20:51So we have some genes that
- 20:53are less commonly mutated,
- 20:55but they cost.
- 20:57They have a much higher risk of
- 20:59cancer and then some others that
- 21:01are left that are more common,
- 21:03but yet their risk of cancer is not as
- 21:05high as you did with the other ones.
- 21:07So that's also important to keep in
- 21:09mind and will see in a minute how
- 21:11we are looking at this differently
- 21:13depending on the jeans.
- 21:14For the most part,
- 21:16the majority of the colon cancer
- 21:18syndromes are autosomal dominant
- 21:20public process and attenuated forms.
- 21:23Lynch syndrome.
- 21:24Those are autosomal dominant,
- 21:26maybe meaning that.
- 21:27The single a little a single imitation
- 21:30encrypted either from mum or that
- 21:33is enough to carry that mutation
- 21:36that causes the the syndrome.
- 21:38That's the majority again,
- 21:40or the colon cancer syndromes.
- 21:43But then there's a couple of them.
- 21:44One is map and we'll talk about it
- 21:46in a second and then this MTH L1,
- 21:49where those are autosomal recessive diseases.
- 21:51That means that we did.
- 21:52We need to inherit 1 mutated copy
- 21:55from Mom and one from that in
- 21:57order to really have the disease.
- 22:00Loser again, less common.
- 22:01The majority of the colon cancer
- 22:04syndromes Paris autosomal dominant.
- 22:07So let's go a little bit over about
- 22:09Lynch syndrome model and what we
- 22:11can do once we have it diagnosed.
- 22:13So the theology we talked about it,
- 22:15it's a mutation in the germline that
- 22:17means that it's inherited in any one
- 22:20of these genes that are called mismatch
- 22:23repair genes to summer dominant.
- 22:25As we mentioned,
- 22:26with variable penetrance and
- 22:27will go through this in a second
- 22:30and miniature diagnosis is wide.
- 22:32Wiley variable as will also see in a minute,
- 22:35but in general lower than
- 22:37sporadical rectal cancer,
- 22:38so we will see as we saw before,
- 22:41that many of these younger individuals
- 22:44who have a higher percentage of
- 22:46cases that will have Lynch Ingram
- 22:48as opposed to older individuals.
- 22:50Only a few polyps or none,
- 22:51and that's a problem that we often
- 22:53see many times because there are no
- 22:56polyps in people think that there will
- 22:58be no risk for developing colon cancer,
- 23:00and in fact it has very little.
- 23:02To do the number of polyps and
- 23:04development of cancer in Lynch syndrome
- 23:06so it's never a marker for that at all,
- 23:08and we don't pay much attention to it
- 23:10at all and more right side to more
- 23:13than sporadic colon cancers in general.
- 23:15It's 70% of the Sprite.
- 23:17Colon cancers do happen in the
- 23:19in the distal part of the colon,
- 23:21****** sigmoid,
- 23:21and the left side of the colon.
- 23:24Yet in Lynch syndrome is
- 23:25more like a half and half,
- 23:26so many more right sided tumors
- 23:29which do have implications when it
- 23:31comes to screening and surveillance.
- 23:33And very rapid cancer development.
- 23:36That's a key characteristic that
- 23:38cancers do develop very fast within
- 23:41two to three years we can go from.
- 23:43Early lesion to a cancer and that
- 23:45really informs how we do screening and
- 23:48surveillance for those individuals at
- 23:50high risk of having a second cancer.
- 23:53In this case,
- 23:54a second colon cancer,
- 23:5630% at 10 years after the first diagnosis.
- 23:58That's why it is very important to
- 24:01either do very enhanced surveillance
- 24:03or even proceed with colectomy after
- 24:06we have a diagnosis of a colon
- 24:09cancer related with Lynch syndrome.
- 24:11And truly,
- 24:11this is not a colon cancer syndrome.
- 24:13This is a multi cancer.
- 24:14In Rome with higher risk for cancer
- 24:17from the Mitchell but also variants
- 24:20stomach small bowel hepatobiliary
- 24:22there ourselves a different number
- 24:24of up types of cancers that have an
- 24:27increased risk and will sinnamon it
- 24:29right here and so over the last few
- 24:31years we've really learned is that
- 24:33lynching room does have many flavors,
- 24:36and those really depend a lot on
- 24:38the type of mutation that we have.
- 24:40Here we have the four genes implicated
- 24:43in Lynch syndrome here on the.
- 24:45Left side we have the column with
- 24:47the different cancer sites and
- 24:49then on the right side.
- 24:51Here we have the cumulative risk
- 24:53for that for diagnosis to a lifetime
- 24:55for the general population just
- 24:57for comparison purposes.
- 24:59And as you'll see here,
- 25:00for colorectal cancer,
- 25:01very high risk in MLH one message,
- 25:04two carriers a little less for MSH
- 25:066 and definitely lower risk for PMS
- 25:09two definitely much higher than the
- 25:11general population or population.
- 25:144.2% over live.
- 25:15Time and here PMS two up to 20%,
- 25:19but definitely less than the other one,
- 25:20so that's also we mentioned that
- 25:23it's a difference that we take into
- 25:25account and to meet real cancer.
- 25:27There are important differences too.
- 25:29Also with the lower.
- 25:33Percentage of individuals developing
- 25:35it when they have PMS two mutations
- 25:38and then there are also very a unique cases.
- 25:41For instance when it comes to the
- 25:44urothelial tract, renal pelvis,
- 25:45ureter, bladder,
- 25:46where we see kind of a clustering
- 25:49of the individuals and families
- 25:51with these cancers.
- 25:53In mutation carriers for MSH.
- 25:562 genes.
- 25:57So that's where they really tend
- 26:00to concentrate.
- 26:01Or for instance in pancreas,
- 26:02where this really has been much
- 26:05more clearly associated with Emily
- 26:07to one mutation carriers and much
- 26:09less with the
- 26:10other ones, and definitely not with PMS two.
- 26:12So we are left with those very important
- 26:15differences that really are informing us
- 26:17on how we are approaching Lynch syndrome.
- 26:20Again, we no longer calling syndrome as a
- 26:24whole and we tend to say more like MLH.
- 26:27One related Lynch syndrome or PMS
- 26:302 links in there just because.
- 26:32They seem to have a important enough
- 26:35differences as you are seeing here
- 26:38and when we look at these one P M S2,
- 26:41which as we mentioned is the one
- 26:43that is the most common of them all.
- 26:45The risk is really concentrated in
- 26:48colorectal and endometrial plus
- 26:49minus 4 Berry and definitely does
- 26:51not seem that there's an increased
- 26:53risk for all these other cancers.
- 26:55So our surveillance is definitely different.
- 26:57Looking at these cancer risks
- 27:00when we are looking at.
- 27:03Average age at presentation.
- 27:05Important differences here too.
- 27:07And when we look at Colon
- 27:09that's younger for Emily Joanna.
- 27:11Message 2 mutation carriers.
- 27:14Yet it's older for MSH 6IN,
- 27:18particularly for PMS two individuals.
- 27:20And if you look at here at the
- 27:23bracket here for PMS two 6166 it's
- 27:25important to remember right now.
- 27:27Last year the average age of
- 27:29colorectal cancer had gone down
- 27:31to 67 in the US population.
- 27:33So that's pretty close to what we
- 27:35would see with PMS two mutation
- 27:37carriers so many times you'll see me
- 27:39individuals Lynch syndrome due to a
- 27:41PMS two mutation that you will be
- 27:44not very spectacular and the age of
- 27:47onset is not going to be that different
- 27:50from the general population and and
- 27:52often we may not even suspect that
- 27:54the patient can actually have Lynch syndrome.
- 27:57When it comes to individual cancers,
- 27:59he just seemed to be a little more equal.
- 28:01Here when it comes to age of
- 28:03presentation of these cancers
- 28:05around all the different genes.
- 28:07So what do we do?
- 28:08And in terms of surveillance.
- 28:10So for colorectal we do start with high
- 28:12quality and meaning high quality colonoscopy.
- 28:15What it really means is that we need
- 28:18to make sure that the preparation
- 28:21is adequate and optimal.
- 28:23Then, uh,
- 28:24and also that endoscopies do spend
- 28:26the time really carefully looking
- 28:28at the at the colon to make sure
- 28:31that we're not missing anything,
- 28:33because,
- 28:34again,
- 28:34particularly right side lesions often
- 28:36would start very flat and may be
- 28:39easily missed and into three years
- 28:41we have a full blown cancer there,
- 28:43so very, very important.
- 28:45The quality of the call and ask
- 28:48be leading at ages 20 to 25, but.
- 28:50At 30 to 35 for the mutation carriers
- 28:53of MSA CHEEKS and PMS two just because
- 28:56of what we were showing before,
- 28:59which is that they tend to present
- 29:01later in life or if.
- 29:04To five years prior to the earliest
- 29:06colorectal cancer in the family.
- 29:08If that was diagnosed before the age
- 29:11of 25 or again. 34 M SH6 or PMS.
- 29:13Two carriers.
- 29:14So looking at this specific genetic
- 29:16defect and also the family history
- 29:19and what's happened
- 29:20with them. And we repeated every
- 29:22one to two years and again.
- 29:25The reason for that is because of
- 29:27how fast it cancers do develop,
- 29:29and there's good studies showing that
- 29:32repeating it every one to two years.
- 29:34The great majority of the cancers
- 29:36get caught right in time.
- 29:38At early stage the majority being able to be.
- 29:43Taken out in this copy clean
- 29:46then causing minimum.
- 29:47This disruption.
- 29:48Doing it this way and not finding
- 29:50them advanced cancers when it comes
- 29:53to stomach and small bowel cancer.
- 29:55We've seen a lot of variability
- 29:57depending on the continent and and
- 29:59that repeats everywhere actually.
- 30:00So the the incidence of overall incidents in
- 30:03the different regions of the world does also.
- 30:07Playing a role in the development of
- 30:09cancer in Lynch syndrome patients too.
- 30:11So for instance.
- 30:13Here in EU.
- 30:14S This really the risk is
- 30:17not that spectacularly high,
- 30:19and the server and surveillance
- 30:22has really not been shown to make
- 30:25a significant difference because,
- 30:28uh, because again,
- 30:29because of the risk not being that high,
- 30:32but certainly for individuals or
- 30:34families who are of Asian descent.
- 30:36We definitely an ask for EGD,
- 30:40with extended within OSCA P
- 30:42every three to five.
- 30:44Years beginning at 40 and every
- 30:46three to five years and the uh,
- 30:49there's some recent data that
- 30:51probably suggests that for the given,
- 30:54the small risk and the little that is added,
- 30:57adding any detour,
- 30:58colonoscopy probably doesn't make sense
- 31:00to do that for the overall population.
- 31:03But again, there's no strong data
- 31:05showing that baseline Helicobacter pylori,
- 31:07testing and eradication.
- 31:09We do that.
- 31:10We don't.
- 31:10We do not want to carcinogens
- 31:13heading back there.
- 31:14Tyler is a underlines,
- 31:16a gastric cancer and certainly we
- 31:18don't like to have a carcinogen
- 31:20on top of a susceptibility of
- 31:23colorectal of gastric cancer.
- 31:25So we try to test and eliminate.
- 31:27You know,
- 31:28individuals who test positive when
- 31:31it comes to endometrial cancer.
- 31:32No good data proving benefit from screening,
- 31:36but we do know that intermedia
- 31:38biopsies are highly sensitive and
- 31:40specific as diagnostic procedures,
- 31:42and that's what's being used
- 31:43every one to two years.
- 31:44Starting at age 30 to 35, trans.
- 31:47Vaginal ultrasound which is.
- 31:49Uh,
- 31:50used for Varian Cancer in premenopausal
- 31:53women is not recommended and
- 31:55hysterectomy is definitely a risk
- 31:58reducing option that works well
- 32:01and being well proven and it
- 32:03really needs to be typed in an
- 32:06individualized way and really trying
- 32:08to see if that can be done right
- 32:11after childbearing age is completed,
- 32:13but family history is important and
- 32:15genetic defect is important in order
- 32:17to really putting it all together and.
- 32:19And and counseling on when it's the
- 32:21right time for that hysterectomy.
- 32:24For ovarian cancer we mentioned
- 32:26before trans vaginal ultrasound or
- 32:29see a 125 are being used and we
- 32:31do know also that bilateral self
- 32:33Ingle S pingo fracta me definitely
- 32:35reduce the incidence of ovarian
- 32:37cancer and we would not do it for
- 32:40PMS two carriers because probably
- 32:42there's no increased risk
- 32:44in this group as we saw
- 32:46before for pancreas cancer.
- 32:47As we mentioned before,
- 32:49very clustered around.
- 32:50Emily Quan, I'm about this gene and
- 32:52that's the one that when there's a, uh,
- 32:55a family member who's had pancreas cancer.
- 32:58In this, have that mutation really
- 33:01recommend screening starting at age 50
- 33:03or 10 years earlier than the youngest
- 33:05pancreas cancer in the family for
- 33:08individuals with more than one first or
- 33:10second degree relative with pancreas,
- 33:11and they know carcinoma
- 33:14GUR still very unclear.
- 33:16Remember we talked that there's
- 33:18a lot of class ring around the.
- 33:20Gene and no,
- 33:22no clear evidence to support screening,
- 33:25but annual urinalysis is usually done.
- 33:28It's a cheap method and and there's
- 33:31some sporadic data that shows that
- 33:34that's been able to help in terms
- 33:37of identifying early lesions.
- 33:39Or as CNS cancer,
- 33:42which also for lynching there's a
- 33:45slightly increased risk annual physical
- 33:47examinations without neurological exam
- 33:49starting at age 25 and 30 is recommended,
- 33:53and yet we don't have strong data on that,
- 33:55and particularly because the risk
- 33:57is not that extraordinary high.
- 33:59How about surgical management?
- 34:01For once colon cancer is diagnosed there
- 34:04should be strong consideration for subtotal,
- 34:07subtotal colectomy.
- 34:08Uh and Elyria earlier Ecklund as Thomas is,
- 34:13and that's because again what we
- 34:15mentioned before the very high
- 34:17risk of developing another cancer.
- 34:19So it is important that surgeons
- 34:21do have it diagnosis before the
- 34:24upgrade and but again,
- 34:26as we mentioned before,
- 34:27if we are going to be of our patients
- 34:29are going to be very compliant and
- 34:31willing to have this colonoscopy
- 34:33every one to two years.
- 34:34That's a reasonable option too.
- 34:36But again, knowing that we do have
- 34:38a pretty high risk once we had.
- 34:40One colon cancer of developing a
- 34:43second one prophylactic surgery.
- 34:44Definitely,
- 34:45as we mentioned before,
- 34:46hysterectomy offer ectomy should be
- 34:48discussed with mutation carriers.
- 34:50After completion of childbearing age
- 34:52or also depending on the on the family
- 34:56history and situation that could
- 34:57be even earlier and we do know that
- 35:01that reduces endometrial and ovarian cancer.
- 35:03A prophylactic colectomy
- 35:05has not been recommended,
- 35:07but in chemo prophylaxis
- 35:08is used and we do use.
- 35:10That we have good data and and two
- 35:13adult aspirins a day for at least
- 35:15a year and a half of continuing
- 35:17intake every day with a significant
- 35:20reduction in colorectal cancer.
- 35:22The problem is that toxicity of two
- 35:24adult aspirins is quite significant,
- 35:27particularly among the older individuals.
- 35:30So we do individualize the option
- 35:33here and also we really pending on
- 35:37more data on lower doses particularly.
- 35:40Now there are studies are looking at one,
- 35:43an adult aspirin and one baby aspirin a day.
- 35:47If see if they do have that effect.
- 35:49Because certainly baby aspirin has been
- 35:51shown to reduce colorectal cancer in
- 35:54the sporadic population quite dramatically,
- 35:56so we're hoping that lower doses will
- 35:58also have a significant effect among
- 36:01individuals who have Lynch syndrome.
- 36:03Switching gears,
- 36:04much less common but certainly
- 36:07very significant morbidity
- 36:09and mortality, and these APC gene.
- 36:12It's causing familial other matters purposes,
- 36:14with the very first gene that was
- 36:17identified to cause the GI Cancer syndrome.
- 36:21This is not a simple dominant disease again,
- 36:23so we just one mutated.
- 36:25A little is enough to cause the disease.
- 36:27Individuals develop hundreds
- 36:29to thousands of other numbers,
- 36:31polyps the penetrance is very,
- 36:33very high for both adenomas and cancer.
- 36:36Almost everyone if we don't remove
- 36:38the colon and cancer develops again
- 36:40in almost 100% of cases by the 40s.
- 36:43If there is no collective before that,
- 36:45the onset of the disease,
- 36:46usually in the teens and the noble
- 36:49mutations are common cause to 30%,
- 36:51we may see at the noble mutation
- 36:53meaning that there is no family history
- 36:55and all of a sudden this patient
- 36:57does have a mutation from that on.
- 36:59These individual can transmit
- 37:01that mutation to the offspring,
- 37:03so that's very different from Lynch syndrome,
- 37:05where the immense majority of
- 37:08the cases are funding vacations.
- 37:10They've been that happened many
- 37:13generations ago, so there's a almost.
- 37:16Always a family history and and family
- 37:20members who will have the mutation
- 37:23when it comes to cancers in faps.
- 37:26The great majority of individuals
- 37:28will have their colectomy before they
- 37:30develop cancer and they do well,
- 37:31but this is really the biggest nightmare
- 37:34for us taking care of these patients,
- 37:36which are the duodenal cancers?
- 37:395 to 11% of these individuals
- 37:42do develop these cancers and.
- 37:46Uh, and uh and they are important.
- 37:48A cause of mobility and the most
- 37:51important cause of mortality nowadays.
- 37:53There are other cancer type pancreas
- 37:55or thyroid or middle blastoma.
- 37:57An inhibitor blastoma,
- 37:59particularly in very very young kids,
- 38:01but the risks are not extremely high.
- 38:05But anyway, something to pay attention to.
- 38:08And interestingly, there's these.
- 38:12Lose association that we call genotype
- 38:15phenotype meaning depending or where
- 38:17the genetic defect in this genies we
- 38:20may have different manifestations.
- 38:22For instance desmoid tumors.
- 38:24This this connective tissue tumors
- 38:26that often can be a true nightmare for
- 38:29patients with faps because of their
- 38:32their Mass Effect pushes other organs,
- 38:35particularly in the abdomen.
- 38:37Those are usually clustered in the three
- 38:40prime region of the gene with other.
- 38:43A characteristic like Garner
- 38:45syndrome with a soft tissue tumors
- 38:48that those will be much more often
- 38:50seen when they are found in meat.
- 38:53They are found in medications and
- 38:55what we call the Mediator, Mediator,
- 38:56cluster region in the action.
- 38:58The last action of the gene.
- 39:01So at any rate,
- 39:02forms usually clustering and mutations
- 39:04in the five prime end of the gene two.
- 39:07So there's some correlation
- 39:09between where the mutation is and
- 39:12what the actual phenotype is.
- 39:14Though this is far from perfect
- 39:17and this is a little bit harder.
- 39:20Be arguably almost anyone when we see
- 39:23all these problems really suspect
- 39:25easily that the patient may have faps,
- 39:28but,
- 39:29uh,
- 39:29but attenuated faps is is much
- 39:32more complicated issue.
- 39:34Usually it's less than 100 polyps,
- 39:36located predominantly in the
- 39:38right colon and and those are
- 39:41policies that add up over time and many
- 39:43times we do see patients who develop
- 39:4620 polyps now and 15 polyps later,
- 39:49and often we just done added app and
- 39:51say well this is looking like there
- 39:54is something going on and they it may
- 39:56be a form of attenuated polyposis.
- 39:58So important to suspect when we
- 40:01have particularly a number of
- 40:03polyps that's in the 20s.
- 40:0530 uh, because then suspicion
- 40:07for that should be high.
- 40:09The answer of polyps and cancers,
- 40:11usually ten years later,
- 40:13on average than faps and and.
- 40:16But again, there's a lot of variability here,
- 40:18and these individuals do also
- 40:21develop funding gland polyps,
- 40:23often in the stomach, and they can proceed.
- 40:26The development of colon polyps,
- 40:27so particularly when we do and asked
- 40:29is where we see funding line polyps in
- 40:32individuals who do not have protein.
- 40:35I'm thinking there's there
- 40:37goes an anti acid medication.
- 40:39Strong antacid medications,
- 40:40which they also cause funding lamb polyps.
- 40:43Then we suspect that there could
- 40:45be some form of Poly policies
- 40:47and we need to pursue that.
- 40:49So what do we do when we have
- 40:52it diagnosed individual with a
- 40:54with a mutation in the APC gene?
- 40:57Well, we start colonoscopies at each.
- 41:0115 and every 12 months.
- 41:05In dumb.
- 41:06Once, uh,
- 41:07the number of polyps becomes too
- 41:10overwhelming to be able to really
- 41:13keep up removing those polyps.
- 41:15Then that's when surgery is
- 41:17indicated in those cases,
- 41:19and and there are two options,
- 41:21one of them is collecting with ileal
- 41:25rectal anastomosis, particularly,
- 41:26the ****** is not very effective
- 41:29with a lot of polyps,
- 41:31and then the ****** need
- 41:32surveillance every 6 to 12 months.
- 41:34With sigmoid,
- 41:34osca,
- 41:34P or the other option is a little
- 41:37pouch channel.
- 41:38Analyzed Moses and uh,
- 41:39and in this case the ****** is gone too.
- 41:43But what the pouch which is made
- 41:46of small bowel does develop.
- 41:49Or that's a often develop
- 41:52polyps in there too,
- 41:54and that needs to release as much
- 41:56as the other as much as the dealer
- 41:59rectal anastomosis wants to.
- 42:00And if there are large or flat
- 42:03lesions or lesions with bill,
- 42:04is Histology or high grade
- 42:06dysplasia then those need to match.
- 42:08Closer surveillance when it comes to
- 42:11duodenal periampullary cancer again.
- 42:14Small bowel cancers.
- 42:15One of the biggest nightmares
- 42:17that we have with FAP patients.
- 42:20We do upper endoscopy with side
- 42:22viewing scopes to make sure that we
- 42:25see well the Impala of batter batter,
- 42:27which is one of the main
- 42:30problems developing adenomas and
- 42:32later cancers in that area.
- 42:34And we do start starting around age 20 to 25.
- 42:39For gastric cancer prevention,
- 42:40as we mentioned,
- 42:42many of these patients with FFP
- 42:44do have funded gland polyps and
- 42:46if they have even focal low
- 42:48grade dysplasia and none of them
- 42:50are particularly large they are
- 42:52tend to be very benign and they
- 42:54won't transform into cancer.
- 42:55Now we we see some of them that are
- 42:57too large or larger than one centimeter
- 43:00or they have read displeasure then the
- 43:03risk of cancer does increase and and we
- 43:06may end up even indicating distract me so.
- 43:09Very important to follow that app
- 43:11even though the majority of cases do,
- 43:13they behave never nine.
- 43:15Wait and for thyroid cancer risks
- 43:17the recommendation is ultrasounds
- 43:19and repeating them every two to
- 43:22five years just to make sure we're
- 43:24not missing anything there.
- 43:25For the attenuated forms,
- 43:27it really what informs what we do
- 43:30really depends on the Poly burden.
- 43:32And as we mentioned,
- 43:34there's a great variability.
- 43:36Some of them have a Poly burden
- 43:39that it's very.
- 43:41Relatively easy to handle,
- 43:42and the scopic Lee,
- 43:43meaning that we can remove good number
- 43:45of problems every time we do colonoscopy.
- 43:47Then we just do colonoscopies and
- 43:49polypectomy everyone to two years
- 43:51and in many cases will be able
- 43:53to keep up with those polyps and
- 43:55there will be no need for surgery.
- 43:57After endoscopy again needs to be
- 43:59done for the small bowel cancer
- 44:02risk and adenomas and Anne Anne.
- 44:07At Chemoprevention is another
- 44:08option here and Slingback is the
- 44:11most well established A1 and this
- 44:14is particularly use and it's very
- 44:17much focused on individuals who
- 44:20already had surgery in who have
- 44:22either remaining ****** or pouch
- 44:24to try to reduce the development
- 44:27of products in this area.
- 44:29When we have a Poly burden that
- 44:31we just can't handle in this
- 44:34completely anymore then that's when
- 44:36we will suggest colectomy again.
- 44:38We see there a erectile anastomosis
- 44:42or proper colectomy,
- 44:44and the creation of the pouch.
- 44:46So it's really how the patient
- 44:48behaves in terms of how,
- 44:50how many polyps the patient develops,
- 44:53how fast they developed,
- 44:54and that will really informs us if we
- 44:57can really keep up with removal and
- 45:00topically or at some point we decide
- 45:02that that's not safe anymore and we
- 45:04need to proceed with the surgery.
- 45:06And this is the newer a Poly process.
- 45:10One of the newer polyposis syndromes
- 45:12that we're less familiar with,
- 45:14uh, that we called MAP or myh
- 45:17associated public process.
- 45:18Remember,
- 45:18we talked that this is an auto somal,
- 45:20recessive meaning that we do need mum,
- 45:23and that mum the budget for mum
- 45:25and the budget from that in order
- 45:28to really have the disease.
- 45:31That means that most of the
- 45:32time we would skip generations,
- 45:34so mum and that would not have
- 45:36the disease yet.
- 45:37You could have sibling schools,
- 45:38have it if they inherited both
- 45:40bad genes from mom and Dad.
- 45:42So,
- 45:42but a third close to a third of
- 45:44patients who have a typical familiar
- 45:47level numbers public process,
- 45:49we know that they look like adenomatous
- 45:51polyp policies and do not have an
- 45:53APC mutation where they will have is.
- 45:54Actually these two mutations in
- 45:56the emoji and a quarter of the
- 45:59patients who have between 10 and
- 46:01100 women of 30 polyps will have
- 46:04my limitations in their bodies.
- 46:06So particularly in these individuals.
- 46:08That looked more like attenuated polyposis.
- 46:11That's where the that the the, the,
- 46:13the line is a little bit blurred
- 46:16with the attenuated forms of IPC,
- 46:19the age of onset, 40s, fifties,
- 46:21risk of cancer. Very, very high,
- 46:24almost complete penetrance by age 60,
- 46:27not 40 like in every people.
- 46:29Page 60 the great majority,
- 46:31if they did not have their polyps
- 46:34removed or surgery removed,
- 46:36and the big the main differences between.
- 46:39AMFAP and a map again.
- 46:42The dominant a pattern versus recessive
- 46:45pattern for a map number of polyps.
- 46:49Again for faps.
- 46:51Typical faps more than 100 polyps for
- 46:55map smaller number less than 100.
- 46:58Many times.
- 46:59Agent diagnosis older for map and a big
- 47:03difference in extra colonic disease,
- 47:05particularly upper GI tract
- 47:07adenomas and cancer.
- 47:09You know, as opposed to the
- 47:11very very high numbers for FAP,
- 47:13and that's made two more the same thing.
- 47:15So much,
- 47:15much lower incidence of both upper
- 47:17GI tract cancers and desmoid tumor's.
- 47:20Big difference from that standpoint,
- 47:22but risks certainly very hyper
- 47:25correctly cancers we saw before
- 47:27for both FP and and MAP and the
- 47:30three minute surveillance is really
- 47:32very very much the same as what
- 47:35we do with that invated faps,
- 47:38which again if we can keep.
- 47:39Up with Poly prayer,
- 47:40the pilot burden through at the
- 47:42scopic removal. That's what we'll do.
- 47:44And if at some point that's
- 47:46not feasible anymore,
- 47:47that's when will suggest surgery,
- 47:50so not much different from
- 47:52the attenuated forms finally,
- 47:54so ready polyposis syndrome.
- 47:57This is a thread piloting the
- 47:59right side of the column.
- 48:01This is the syndrome that
- 48:03we've defined for years,
- 48:05and yet at this point we really
- 48:07don't have a genetic defect
- 48:08that's associated with it.
- 48:10There's some some jeans have been
- 48:13a loosely associated with it,
- 48:16but really no strong data on that either,
- 48:19which makes things very challenging
- 48:21when it comes to really having a
- 48:24unified approach to a disease when we
- 48:27really don't have a clear theology.
- 48:29The inheritance pattern is unclear,
- 48:31some data has pointed at us
- 48:34all dominant type of pattern,
- 48:37but other data has pointed towards
- 48:40and formal recessive.
- 48:42Patterns who are really still unclear
- 48:45and the numbers in in these cases
- 48:48do coexist with shredded polyps too,
- 48:51so it's not all about rated polyps,
- 48:54and most of them will find
- 48:55a mix pattern of polyps.
- 48:57The miniature of colorectal cancer
- 48:59diagnosis is 55 and relative
- 49:01risk of cancer 5.4 on average,
- 49:04and maybe there seems to be
- 49:06some different phenotypes,
- 49:08some of them being more severe
- 49:10with large right side.
- 49:11This isolated at the nomads and.
- 49:13Young age of onset, but again every time,
- 49:16but we don't have a specific
- 49:18gene that's behind the disease.
- 49:20Often it's less.
- 49:21It's a little bit more challenging
- 49:23to really have a unified idea
- 49:24of what's going on,
- 49:25and we've got by this clinical
- 49:28criteria that were originally set
- 49:30up by the World Gastroenterology
- 49:33organization that will revise in 2019,
- 49:35or basically as looking at number
- 49:38of serrated lesions in the colon
- 49:41and the size of these lesions.
- 49:44That we really kind of helped
- 49:46us classifying patients do have
- 49:48several Poly process or not.
- 49:50There's nothing magic about these
- 49:52criteria and actually the criteria
- 49:54got a little bit loose and because
- 49:57we're missing a lot of cases that
- 49:59were not fulfilling in 2010 criteria
- 50:01and yet they were developing cancer
- 50:04at similar rate as as the other ones.
- 50:07Therefore, that's how that got changed.
- 50:09And the biggest change is really counting
- 50:12serrated and hyperplastic lesions.
- 50:14A proximal to the ****** instead
- 50:16of proximal to the sigmoid colon
- 50:19when it comes to counting.
- 50:21Accounting for these lesions for
- 50:23this rare public process and so on.
- 50:27What we do in terms of surveillance.
- 50:29Colonoscopy with polypectomy until
- 50:31all polyps that are larger than 5
- 50:34millimeters are removed and then
- 50:36with that more clear colon we
- 50:38would repeat colonoscopy.
- 50:40Went to three years depending on number
- 50:42and size of polyps, and certainly.
- 50:44If there's no good way to keep
- 50:46up with this polyps and again,
- 50:49it's tricky because some of these are
- 50:50very flat and hard to see sometimes.
- 50:52Then, consider surgical referral,
- 50:55particularly if we find that evidence
- 50:59of hybrid displeasure in those cases,
- 51:02so the this is a list of a Poly process
- 51:08syndromes that, as you can see,
- 51:10the number of genes that are associated
- 51:12with them has grown over the last few years.
- 51:16Even though many of them are really
- 51:18not that frequent,
- 51:19we've mentioned about APC causing faps
- 51:23and the attenuated form myh causing map.
- 51:26Then this might less common these
- 51:29people polymerase proofreading
- 51:31associated Poly process due to
- 51:33this genetic germline defects,
- 51:34gram one for hereditary mix Poly poses
- 51:38or these other anti NTHL one and then
- 51:41the hammer tomatoes fully process
- 51:42that we've known for years because
- 51:44of their very unique phenotypes.
- 51:45Boots jiggers.
- 51:46Juvenile Poly policy is piton
- 51:48hammer toma tumor syndrome,
- 51:50Cowden for instance.
- 51:51Those I'm not gonna get into right
- 51:54now to basically I think just to
- 51:56leave you with this that when it
- 51:59comes to Poly process,
- 52:00things are not more often not clear cut.
- 52:03We may have FAP patients who would
- 52:06have not only I'm at this point
- 52:08but also so Reddit polyps,
- 52:10serrated polyp poses usually does include
- 52:13a lot of patients or patients who have.
- 52:16Not only is really pose,
- 52:17but also the number this polyps.
- 52:19So at mix type of polyps is very
- 52:22commonly seen in many of those
- 52:25syndromes and I'm so grateful.
- 52:27And that's,
- 52:29uh,
- 52:29that's important to remember and and will.
- 52:34I will leave it here and then at the
- 52:36end will be happy to take any questions.
- 52:38Thank you very much.
- 52:42Alright, thank you so much Doctor Lohr.
- 52:45Next I'd like to introduce
- 52:47Doctor James Farrell.
- 52:48Dr Ferrell is an expert in
- 52:51pancreatic disease treatment,
- 52:52and research is board
- 52:54certified in internal medicine,
- 52:56gastroenterology in clinical pharmacology.
- 52:57He leads the Yale Center for
- 53:00Pancreatic Disease at Yale
- 53:01School of Medicine and Yale,
- 53:03New Haven Hospital,
- 53:04as well as the Yale
- 53:06Interventional endoscopy program.
- 53:07Thank you for joining us Doctor Farrell.
- 53:21Doctor Farrell are you there?
- 53:30Can you hear me? Yes, perfect,
- 53:34thank you. Let me get my slides up.
- 53:40Uhm?
- 53:52Quick.
- 53:55Away.
- 54:00Again, good evening everybody.
- 54:01Thanks for the invitation to
- 54:03participate again this year.
- 54:05Uh, in this mini symposium.
- 54:08I had actually, uh.
- 54:11We only plan to talk for about 10 or
- 54:1315 minutes because it's late and I'm
- 54:15sure there's other speakers as well,
- 54:17so I'm probably going to keep my
- 54:20comments fairly brief and just cover
- 54:23some of the issues related to screening
- 54:25and prevention for high risk pancreas
- 54:28cancer relatively ultimately focusing
- 54:30on the high risk genetics cases and.
- 54:32Because it's it's not as a mature a topic
- 54:35as perhaps in the realm of colon cancer,
- 54:37which you heard about,
- 54:39or pressure ovarian cancer.
- 54:41You'll see a lot of it is still under
- 54:42kind of the context of research,
- 54:44and I've added my contact
- 54:45information in the last slide.
- 54:47If anybody wants to reach out to
- 54:49me with any additional questions.
- 54:51So let me just put this.
- 54:57Sorry.
- 54:59We get rid of this.
- 55:01There's an annoying bar on my.
- 55:07I don't know where that is
- 55:09that bar on your screen too.
- 55:11Oh here we go, OK? Put that.
- 55:15Let me put that down there OK?
- 55:17So when we think just to remind
- 55:19people we think of pancreatic cancer,
- 55:22you know, compared to some of the other.
- 55:30Here we go. We compared with
- 55:32some of the other cancers.
- 55:34Now we think of the overall
- 55:35incidence of pancreas.
- 55:36Cancer is actually, you know it's low on
- 55:39the list #9 or 10 for both men and women.
- 55:42But the real challenge is of course
- 55:44when it comes to cancer related
- 55:45deaths and it jumps up into the list
- 55:48to number the number 3 or #4 spot.
- 55:50And so you know with, uh,
- 55:52an average of around 56,000
- 55:55cases in the current year.
- 55:59It's guesstimated that by 2030
- 56:01or so pancreatic cancer will be
- 56:03the second most common cause for
- 56:06cancer related deaths, you know,
- 56:07and a lot of that has to do with.
- 56:10More progress that's made in other areas
- 56:12of treatment and particularly prevention
- 56:14and less so with pancreatic cancer.
- 56:16Although there have been some
- 56:18advances in both the areas
- 56:19of treatment and prevention,
- 56:20but just not as dramatic
- 56:22as with other malignancy.
- 56:23So a huge challenge.
- 56:27Uhm? I think it's also worth stating that.
- 56:34It's important to kind of understand the
- 56:36different stages for pancreatic cancer,
- 56:38because this is one of the issues that we
- 56:41have with any sort of surveillance strategy,
- 56:45and so for this particular patient,
- 56:47this is a CT scan,
- 56:49and so for this particular patient,
- 56:51this is a small pancreatic cancer
- 56:54involving the head of the pancreas.
- 56:57Probably the order of 1 1/2 to 2
- 57:00centimeters or so in size, and these
- 57:02are important blood vessels around it,
- 57:03but this mass is actually somewhat
- 57:06distinct from these blood vessels,
- 57:07and so typically a surgeon
- 57:09would be able to remove this.
- 57:10So even though the nomenclature
- 57:12can be quite confusing,
- 57:14this is in a very straightforward way.
- 57:15We think about in terms of
- 57:18resectable pancreatic cancer,
- 57:19you see the liver over here on the left side,
- 57:22and the kidneys as well now.
- 57:24If you move on from that a
- 57:26little bit and again,
- 57:27looking at again another CT scan,
- 57:30you can see in the arrow here.
- 57:33Another large mask,
- 57:34but now this mass is beginning to
- 57:37involve and in case a blood vessel
- 57:40and an important blood vessel here,
- 57:42and for this reason, even though you say,
- 57:44well, it's still confined to the pancreas,
- 57:47or at least the head of the pancreas because
- 57:49of its involvement in a blood vessel.
- 57:51This makes it more difficult for a
- 57:53surgeon to consider removing this.
- 57:55Again, there may not be evidence,
- 57:56at least to the visible eye of disease
- 57:58elsewhere in the liver, and so on.
- 58:00But this still would not be
- 58:01considered surgically resectable.
- 58:03In its current state,
- 58:05and so we call this locally advanced disease.
- 58:09And then the most dramatic stage,
- 58:11of course,
- 58:12is individuals who present with
- 58:14disease outside of the pancreas
- 58:16at the time of presentation.
- 58:18Often it's in the liver,
- 58:20sometimes it's up in the chest,
- 58:22and often sometimes then again,
- 58:23it's in what's called the peritoneum.
- 58:24So implants here shown on this CT scan,
- 58:29so again,
- 58:30this would not be considered surgically
- 58:32resectable removable disease,
- 58:34and would in fact be considered
- 58:37metastatic disease.
- 58:38To put this into some perspective then.
- 58:42Uhm,
- 58:42only about 15% of all patients
- 58:45present with that surgically
- 58:46resectable stage and early stage
- 58:49that a surgeon can go in and remove.
- 58:52And this is the group of patients
- 58:54that really offer the best
- 58:56potential for those that present
- 58:58with at the stage with the cancer.
- 59:00And so the the mean average survival
- 59:02is in the region of 2025 months.
- 59:04But of course there can be
- 59:07extremes with that.
- 59:08For the other two groups,
- 59:09however,
- 59:09it splits somewhat evenly between
- 59:12patients presenting with locally advanced
- 59:14disease as well as metastatic disease,
- 59:17and so it just gets at the important
- 59:19issue that although there are newer
- 59:21treatments and somewhat better medical
- 59:23treatments for this disease than there were,
- 59:26say,
- 59:2615 or 20 years ago.
- 59:29Will focus to make any sort of dent in
- 59:31this disease is really early detection.
- 59:35And part of that reason where it becomes
- 59:38challenging is because of course the
- 59:40symptoms associated with pancreatic
- 59:41cancer are very nonspecific, so.
- 59:43Uhm, you know if you think about
- 59:45them and how these patients will
- 59:48present at the symptomatic point,
- 59:50at least you know abdominal pain.
- 59:52Weight loss are can be common symptoms,
- 59:54but they're very nonspecific.
- 59:55You get abdominal pains
- 59:56when also from a gallstone.
- 59:58It doesn't necessarily have to
- 59:59be a pancreatic malignancy,
- 01:00:01and the same thing for weight loss.
- 01:00:03When you look at other symptoms,
- 01:00:04like jaundice and dark urine,
- 01:00:06know you could certainly kind of begin to
- 01:00:08focus in on things related to the pancreas,
- 01:00:09but still very nonspecific, and again,
- 01:00:12there's other symptoms like nausea,
- 01:00:13vomiting, depression,
- 01:00:15anorexia, but again,
- 01:00:16have a multitude of causes,
- 01:00:18and pancreatic cancer is certainly
- 01:00:20not high up on that list.
- 01:00:23Two ones that are also worth
- 01:00:24thinking about are acute
- 01:00:26pancreatitis and new onset diabetes.
- 01:00:28And we'll come back and talk a little bit
- 01:00:30more about the new onset diabetes later on.
- 01:00:32In terms of ways that patients
- 01:00:34with pancreatic cancer may present
- 01:00:36that we should be familiar with.
- 01:00:39So therefore when we think about the
- 01:00:41goals of pancreatic cancer screening,
- 01:00:43it has been stated in guidelines that
- 01:00:46a successful screening program should
- 01:00:48detect and treat what's considered
- 01:00:50early stage or resectable margin negative.
- 01:00:53So there's no tumor left
- 01:00:56behind pancreatic cancer.
- 01:00:57As well as a lesions that are not cancerous,
- 01:01:01so called precancerous lesions,
- 01:01:02and these include a variety of very well
- 01:01:06established pathologic and entities
- 01:01:08called Pan Inns or IPM nsor MCMS.
- 01:01:12These are types of sometimes
- 01:01:13types of cysts in the pancreas.
- 01:01:16And some of them do have imaging
- 01:01:18carlitz that can be seen on a CT scan,
- 01:01:20but unfortunately some of them don't and
- 01:01:22it can be quite difficult to identify,
- 01:01:24but ideally picking up high grade
- 01:01:28dysplastic precancerous lesions
- 01:01:30would really be a huge step forward
- 01:01:34in the management.
- 01:01:35Prognosis for this group of patients.
- 01:01:39So without getting into it
- 01:01:40in too much detail,
- 01:01:42I'll just state very briefly
- 01:01:44that we do not perform general
- 01:01:46screening in the general population.
- 01:01:49There's a variety of reasons for that.
- 01:01:51There is no simple single
- 01:01:53blood test that you know.
- 01:01:55If you have no risk factors related
- 01:01:57to pancreatic disease, you can get.
- 01:01:58It's not to say people aren't
- 01:02:00working in that direction,
- 01:02:01but it's a very challenging area
- 01:02:02and so right now we don't offer
- 01:02:05or talk about necessarily general
- 01:02:07screening for the general population,
- 01:02:10but we do focus on is trying to
- 01:02:13study an enriching groups and the
- 01:02:16three major groups that we study
- 01:02:18and that we think about when we
- 01:02:20think about pancreatic cancer
- 01:02:22surveillance are pancreatic cysts,
- 01:02:24diabetes,
- 01:02:24and then familial pancreatic cancer.
- 01:02:27Very briefly,
- 01:02:27I'm not going to spend much time.
- 01:02:29Talking about pancreatic cysts,
- 01:02:30but pancreatic cysts are exceedingly common,
- 01:02:33so anywhere between you know 10 to
- 01:02:3540% of CT scans and MRI's that are
- 01:02:38done for patients coming into hospital
- 01:02:40and hospital will have a small cyst.
- 01:02:42The vast majority of assists
- 01:02:44will not develop into cancer,
- 01:02:45but most of those cysts can actually
- 01:02:47be can be considered precancerous
- 01:02:50when you think at a national level.
- 01:02:52It's guesstimated that probably
- 01:02:54around 6 million. Individuals in EU.
- 01:02:56S have some form of pancreatic says,
- 01:02:57so it's not a small, trivial issue.
- 01:03:00The risk may be low,
- 01:03:02but kind of on a global scale.
- 01:03:03It adds up, and so it's something that
- 01:03:06we certainly take note of and have
- 01:03:09guidelines in place to try and manage this.
- 01:03:12Not necessarily the new kid on the block,
- 01:03:14but something that's you're going to
- 01:03:15hear more and more about is the interplay
- 01:03:18between diabetes and pancreatic cancer.
- 01:03:19So for sure,
- 01:03:20for individuals with diabetes,
- 01:03:22it's well known that they are
- 01:03:23at a slightly increased risk of
- 01:03:25developing pancreatic cancer.
- 01:03:27But probably the much more interesting
- 01:03:29direction is the idea of pancreatic
- 01:03:32cancer leading and presenting as diabetes,
- 01:03:36and this is more than just an issue of
- 01:03:38the tumor taking over the pancreatic gland.
- 01:03:41There's some other factors going on here
- 01:03:43that people are beginning to scratch away at.
- 01:03:46And the result may provide actually
- 01:03:48an opportunity for for screening.
- 01:03:52In one perspective case control study
- 01:03:54that was done of a large number of
- 01:03:57newly diagnosed pancreatic duct
- 01:03:58adenocarcinoma is the vast majority of
- 01:04:01patients had some form of fasting blood,
- 01:04:03blue blood, glucose abnormality,
- 01:04:05some of them actually had, you know,
- 01:04:08documented diabetes,
- 01:04:09and about half of them had what's
- 01:04:11called new onset diabetes within a
- 01:04:13period of time before the presentation,
- 01:04:16so this cannot be ignored.
- 01:04:18There's something going on with
- 01:04:20diabetes and pancreatic cancer.
- 01:04:21Uhm, that's worth studying.
- 01:04:24When we look at individuals who
- 01:04:27subsequently have an association
- 01:04:29between pancreatic duct adenocarcinoma
- 01:04:31and elevated blood sugars,
- 01:04:33certain studies have been able to
- 01:04:35go back and track the kind of slow
- 01:04:38eyes of blood sugars anywhere up to
- 01:04:40about 36 months before the clinical
- 01:04:43presentation of pancreatic cancer.
- 01:04:45So this then is being translated
- 01:04:48into another way to try and enrich
- 01:04:51or find certain populations who
- 01:04:53are at higher risk for developing
- 01:04:55pancreatic cancer and study it.
- 01:04:57And so this is very much at
- 01:04:58a research level right now,
- 01:05:00but it is gathering speed.
- 01:05:03The final and big area that I do want
- 01:05:05to talk to you about this evening
- 01:05:07is familial pancreatic cancer,
- 01:05:09so it's guesstimated that when
- 01:05:11you think about all patients
- 01:05:13presenting with pancreatic cancer.
- 01:05:16About a total of anywhere between
- 01:05:1810 or 15% of these patients will
- 01:05:21have either a familial component,
- 01:05:23meaning when you ask them
- 01:05:25about their family history,
- 01:05:26they'll tell you that they have a.
- 01:05:29You know, two first degree relatives.
- 01:05:32One first degree relatives,
- 01:05:33several secondary relatives, and so on.
- 01:05:35So does it.
- 01:05:35I definitely lineages going on in
- 01:05:37that family when you ask it off,
- 01:05:39people forget to ask,
- 01:05:40but I think now people are becoming
- 01:05:42more aware of that and then a certain
- 01:05:44percentage of these patients then.
- 01:05:45We actually have a documented and
- 01:05:48detectable germline mutation that we can
- 01:05:50find in the blood that can further kind
- 01:05:52of steer and guide us about what to do.
- 01:05:55Uhm, when we think about
- 01:05:57familial pancreatic cancer,
- 01:05:58obviously the more family
- 01:05:59members that are affected,
- 01:06:01the greater your relative risk
- 01:06:03of developing pancreatic cancer.
- 01:06:04So if you've got three first
- 01:06:07degree relatives.
- 01:06:08Uhm,
- 01:06:08you have a 32 full relative risk
- 01:06:11compared to individuals who don't
- 01:06:13have that type of family history.
- 01:06:16If you've got one first degree relative,
- 01:06:19it's unclear what the significance
- 01:06:20of that is in terms of whether
- 01:06:22we act upon it or not,
- 01:06:24and so it doesn't meet the definitive
- 01:06:26criteria for saying someone has a
- 01:06:28familial pancreatic cancer comes from
- 01:06:30a familial pancreatic cancer kindred.
- 01:06:32We certainly take notice,
- 01:06:34especially when individuals
- 01:06:35are young and families.
- 01:06:36But again, having just one.
- 01:06:38Family member.
- 01:06:39I probably does not meet those.
- 01:06:41You know definite criteria.
- 01:06:42It's also interesting to note
- 01:06:44that despite a lot of knowledge
- 01:06:47about familial pancreatic cancer,
- 01:06:48and the fact that it runs in the family,
- 01:06:51the entire mode of transmission
- 01:06:54and hardens is still unclear.
- 01:06:56The most common abnormality that's found
- 01:06:59from a genetic perspective is the bracket,
- 01:07:01two mutation,
- 01:07:02but it's still as you can see,
- 01:07:03only found it up to 20% of patients,
- 01:07:06so it's still not a large number of patients,
- 01:07:08and there are probably.
- 01:07:10Other,
- 01:07:10either genes that haven't been
- 01:07:12discovered or or defined yet,
- 01:07:14or some other shared environmental issues
- 01:07:17that we still have to scratch away at.
- 01:07:20So here is a list of the broad familial
- 01:07:22syndromes associated with pancreatic cancer.
- 01:07:25Most of them you will hear about
- 01:07:27in some other form this evening,
- 01:07:29and we've certainly very commonly talked
- 01:07:32about bracket two and bracket one,
- 01:07:36and increasingly recognizing the
- 01:07:38importance of pal B2 as a player in
- 01:07:41familial risk for pancreatic cancer.
- 01:07:44Also,
- 01:07:44pretty girl you heard just Dr
- 01:07:46lower torque talk about hereditary
- 01:07:48nonpolyposis colon cancer.
- 01:07:50A variety of hereditary pancreatitis
- 01:07:52syndromes have been defined as
- 01:07:54risk factors for the development
- 01:07:56of pancreatic cancer and then at
- 01:07:59P-16 has a very large or or fan FA.
- 01:08:01MM is a very large risk factor for the
- 01:08:03development of pancreatic cancer as well.
- 01:08:07Uhm? What we actually do for these patients,
- 01:08:10similar to the other patients that
- 01:08:11we see with pancreatic cysts as
- 01:08:13well as now as we look a little bit
- 01:08:15more closely at new onset diabetes,
- 01:08:16is really kind of performed in
- 01:08:19a multidisciplinary approach.
- 01:08:20Uh, currently?
- 01:08:22The standard approach is to
- 01:08:24start with non invasive imaging,
- 01:08:25either a CT scan or preferably an MRI.
- 01:08:29Depending on what is found,
- 01:08:30then a certain subgroup of patients will
- 01:08:33undergo an endoscopic evaluation to take
- 01:08:35a closer look at the pancreas to look,
- 01:08:38particularly at SIS looking for masses
- 01:08:40and to biopsy suspicious lesions.
- 01:08:42And then worrisome groups of
- 01:08:44patients will ultimately be referred
- 01:08:46for surgery to remove a portion
- 01:08:48of the pancreas that is either
- 01:08:50very concerning or does have a
- 01:08:52documented cancer associated with it.
- 01:08:54So this is done in a very prospective
- 01:08:57multidisciplinary type of approach.
- 01:09:01These are the rules of patients
- 01:09:03that we see in our current high risk
- 01:09:05pancreas cancer surveillance program.
- 01:09:07In our early detection clinic.
- 01:09:10I think about them in terms
- 01:09:11of four broad groups.
- 01:09:12Poutier goes, of course,
- 01:09:13which has a very high risk of
- 01:09:16developing pancreatic cancer.
- 01:09:17We talked about the familial
- 01:09:19pancreatic cancer kindreds.
- 01:09:21We typically start.
- 01:09:23At the age of 55 or 10 years younger than
- 01:09:28the youngest individual in the family,
- 01:09:31and it does require to have two or
- 01:09:34more members with pancreatic cancer,
- 01:09:37one of which is a first degree member.
- 01:09:38So there are some defined criteria.
- 01:09:41Then there are the better
- 01:09:43characterized individuals that, again,
- 01:09:44you're hearing about this evening.
- 01:09:45The germline mutations that have.
- 01:09:48But that must have at least one
- 01:09:50family member with pancreatic cancer,
- 01:09:52so there is a higher group which
- 01:09:55includes P16 bracket, two,
- 01:09:57probably 2 and now ATM is in
- 01:09:59that higher group and a lower
- 01:10:00risk group that we still study,
- 01:10:02which includes the Braca one population
- 01:10:04as well as the HNPCC population,
- 01:10:07but just just remember that for
- 01:10:09the majority of these patients,
- 01:10:10with the exception of P-16,
- 01:10:12it does require there to be some
- 01:10:14family history of pancreatic cancer,
- 01:10:16and then we also mentioned
- 01:10:18hereditary pancreatitis.
- 01:10:19Currently,
- 01:10:19as of this week we have about 205
- 01:10:22patients that we are actively
- 01:10:24managing and following in our high
- 01:10:26risk pancreas surveillance program.
- 01:10:28And again you can see the breakdown there.
- 01:10:30There's a large number that we don't
- 01:10:32have any sort of germline mutation status,
- 01:10:34but a fairly large number have some
- 01:10:36abnormality in a DNA repair gene.
- 01:10:40Just to kind of look at this and say,
- 01:10:42you know this is not as mature
- 01:10:43world as what you're hearing for
- 01:10:45colon cancer and breast cancer.
- 01:10:47Even for ovarian cancer,
- 01:10:48but it is important to say that there
- 01:10:50is involved data and there does
- 01:10:52appear to be data that says support
- 01:10:54surveillance in high risk individuals.
- 01:10:56From the perspective of an improved
- 01:10:59outcome associated with those
- 01:11:01individuals that have cancers
- 01:11:02detected as part of a surveillance as
- 01:11:05opposed to those that just present
- 01:11:07sporadically or with symptoms.
- 01:11:08So at least kind of.
- 01:11:10Early data to support that this is a
- 01:11:13good strategy and does does hopefully
- 01:11:16will improve overall survival in this cohort.
- 01:11:20So I'll finish on that and just
- 01:11:22summarize the important point to note.
- 01:11:24Is that right now we still don't have
- 01:11:26don't recommend general population screening.
- 01:11:30But it is an area that's being worked
- 01:11:32on and there are certain blood
- 01:11:33tests that are either available
- 01:11:35or coming down the pipeline.
- 01:11:36Trying to address this particular issue.
- 01:11:39For pancreatic cancer,
- 01:11:41it's now considered standard of
- 01:11:44care for the appropriate indication.
- 01:11:47Although we have a variety of research
- 01:11:49studies that are open that follow
- 01:11:50this group of patients that involve
- 01:11:52again combinations of imaging with MRI
- 01:11:55or endoscopic ultrasound overtime.
- 01:11:59We talked about pancreatic cysts
- 01:12:00as another high risk group,
- 01:12:01and it's a big volume issue,
- 01:12:03and we've opened a study the ekach
- 01:12:05two and eight five study here at Yale
- 01:12:08to actually study this particular
- 01:12:09group in terms of surveillance and
- 01:12:12different surveillance protocols.
- 01:12:13And I would advise you just to keep
- 01:12:15your eye on the diabetes space for
- 01:12:18this particularly new onset diabetes.
- 01:12:20And maybe we'll be looking at
- 01:12:22combining all these risk factors,
- 01:12:23be it family history,
- 01:12:25pancreatic cyst,
- 01:12:26as well as their blood sugar levels.
- 01:12:29I'll also just give a plug for our
- 01:12:32pancreatic cancer early detection
- 01:12:33clinic that is based with Doctor
- 01:12:36Laura's group at the St Rayfield campus
- 01:12:38and my contact information is there.
- 01:12:40If anybody has any specific questions
- 01:12:42for us over time, thank you.
- 01:12:47Great, thank you so much Doctor Farrell
- 01:12:49up in the interest of time will
- 01:12:51quickly move over to Doctor Ratner.
- 01:12:53UM Elena Ratner is a board certified
- 01:12:56gynecological oncologist with
- 01:12:57special interest in chemotherapy
- 01:13:00targeted drug development,
- 01:13:01patient quality of life programs,
- 01:13:03and early cancer detection,
- 01:13:04she's the director of the discovery to
- 01:13:07cure early ovarian cancer detection
- 01:13:09program and founder and director of
- 01:13:11the Sexuality Intimacy and Menopause.
- 01:13:13Cancer survivorship program
- 01:13:15welcome Doctor Ratner.
- 01:13:17Thank you for joining us.
- 01:13:19Thank you so much Claire.
- 01:13:20It is so great to be here.
- 01:13:22I'm going to share my screen.
- 01:13:25Bear with me. This is frequently
- 01:13:27my Achilles heel. Uhm?
- 01:13:34OK. Oh, this actually seems to have worked.
- 01:13:38This is lovely, so I had the
- 01:13:41privilege today to speak to you
- 01:13:44about UM yet another component of.
- 01:13:51The screening and early detection
- 01:13:53in patients who we consider to be
- 01:13:56at high risk for different cancers,
- 01:13:58hereditary cancers,
- 01:14:00and that being ovarian cancer.
- 01:14:05Once. Here we go.
- 01:14:06So the premise of this that many,
- 01:14:10many have now spoken before me is
- 01:14:13this the driving hypothesis that
- 01:14:15many patients may be at increased
- 01:14:18risk for several cancers based
- 01:14:20on personal or family history,
- 01:14:23genetic status, personal history,
- 01:14:25but typical hyperplasia,
- 01:14:27and it's so important because
- 01:14:29so much in our current culture
- 01:14:31is becoming not about you know.
- 01:14:34Especially you know.
- 01:14:35In, particularly in cancer,
- 01:14:36you know the conversation now is really.
- 01:14:38No longer about what do we
- 01:14:40do to curing cancer,
- 01:14:42and it's not even as much
- 01:14:44about early detection as those
- 01:14:46two had been so challenging.
- 01:14:48A lot of conversations currently
- 01:14:51are about cancer prevention,
- 01:14:53so that is why this risk assessment
- 01:14:55is so important because there are
- 01:14:58options for either surveillance or
- 01:15:00risk reduction for these patients
- 01:15:03and for their family members.
- 01:15:06Uhm,
- 01:15:06and management of these patients
- 01:15:08up to now has been there very much
- 01:15:10piece meal by variety of providers
- 01:15:12in several groups and this is,
- 01:15:14you know,
- 01:15:15they might kind of my passion again.
- 01:15:17In particular,
- 01:15:17brain cancer is that the signs and
- 01:15:20symptoms of being cancer so unique,
- 01:15:22but also still make that patients
- 01:15:25they frequently get seen by different
- 01:15:27providers who do great job ruling
- 01:15:29out there 'cause of the symptoms.
- 01:15:32But do not connect the pieces to
- 01:15:35appreciate that these signs and
- 01:15:36symptoms will vary in cancer.
- 01:15:38And that is why it's so important
- 01:15:39that we come up with a comprehensive
- 01:15:41approach to this patient population.
- 01:15:46So here is a cancer is as clear,
- 01:15:47discussed 10% of all cancers,
- 01:15:50probably higher than that.
- 01:15:52Mutations within a single data jeans.
- 01:15:56But of course, again,
- 01:15:57Astaire discussed whole exome sequencing.
- 01:15:59Our understanding of cancer
- 01:16:01genetics is about to change,
- 01:16:03and this percentage is going to grow.
- 01:16:05In my population,
- 01:16:07the risk factors that we look at
- 01:16:10early age of onset of cancer,
- 01:16:12multiple affected family members
- 01:16:14related cancers in their family and
- 01:16:16again in the world of ovarian cancer
- 01:16:19is so important that we don't forget
- 01:16:21that it's not only women and it's
- 01:16:23not only over impressed that there's
- 01:16:25many other associated cancers,
- 01:16:27such as pancreatic cancer,
- 01:16:29that apparel just so beautifully
- 01:16:31talked about such as Melanoma,
- 01:16:32such as prostate cancer in males
- 01:16:35and for us in in the in, the female.
- 01:16:37Only feels it's always very important
- 01:16:39to remind the patients that when I'm
- 01:16:41asking them about family history,
- 01:16:43I'm not just asking about their
- 01:16:45mom or their grandmother.
- 01:16:46I'm also asking about the
- 01:16:48paternal line as well.
- 01:16:50Multiple primaries,
- 01:16:51male breast cancer,
- 01:16:53Jewish ancestry,
- 01:16:54and then the the subtype of the
- 01:16:56ovarian cancer that they have.
- 01:17:00So I won't go into this,
- 01:17:02but we already heard so much about
- 01:17:04that today, so there's a one BRCA
- 01:17:072 increase the risk of breast,
- 01:17:09ovarian, prostate, and NBRC.
- 01:17:112 increase risk of breast,
- 01:17:13ovarian, prostate in men,
- 01:17:15as well as pancreatic cancer
- 01:17:18and male breast cancer.
- 01:17:20The these genes increase the risk
- 01:17:22of cancer space substantially,
- 01:17:24so breast cancer,
- 01:17:25being the most common as high as
- 01:17:2885% black 180% bracket two and
- 01:17:32then as high as 60% for Brock and
- 01:17:35one for the risk of varying cancer
- 01:17:37and as high as 40% for bracket.
- 01:17:40Two in in ovarian cancer in bracket 2.
- 01:17:50And the estimated lifetime
- 01:17:52cancer risks of other cancers,
- 01:17:54such as pancreatic and prostate.
- 01:17:56Male breasts, are also, as you know,
- 01:17:57increased with again as high as
- 01:18:00doubling for prostate cancer increasing.
- 01:18:03Again, it's like apparel,
- 01:18:05just talked about,
- 01:18:06and then five to 10% in male breast cancer.
- 01:18:11So I'm going to jump into the
- 01:18:12garage cancers because again,
- 01:18:14you have heard so much already about other
- 01:18:16cancers and risk for the genetic mutations.
- 01:18:18So I will talk about ovarian cancer.
- 01:18:20Ovarian cancer is not the most
- 01:18:22common kind of classical agency.
- 01:18:23The most common cause malignancy
- 01:18:25is the uterine cancer,
- 01:18:26but it's by far the deadliest.
- 01:18:29There's 22,000 cases they
- 01:18:31get diagnosed every year,
- 01:18:33and 15,000 women die every year.
- 01:18:37So as much as much as we have tried,
- 01:18:39you know this is not for the lack of trying.
- 01:18:42A lot of research has got in
- 01:18:43to be in cancer management.
- 01:18:45A lot of research has gone into
- 01:18:48chemotherapy regimens and resistance,
- 01:18:52chemotherapy resistance regiments,
- 01:18:55and we've done so much research and so much
- 01:18:59advancement and surgical cancer management.
- 01:19:03You know I can now do surgeries.
- 01:19:04Laparoscopic Lee where
- 01:19:05women go home same day.
- 01:19:07Where in the past you know five years back
- 01:19:09women will help would have a huge incision.
- 01:19:12On their bellies, and would stay in
- 01:19:13the hospital longer than a week.
- 01:19:14So so the field is moving and
- 01:19:17things have have have been done,
- 01:19:19but sadly it has not moved the
- 01:19:22mortality of this disease,
- 01:19:24and that is unacceptable.
- 01:19:26The big part of this challenge in
- 01:19:28improvement in mortality is again the
- 01:19:31staff that unfortunately this cancer
- 01:19:33is continue to be diagnosed at a later stage.
- 01:19:37I will talk a little bit about
- 01:19:38difficulty of this and why this
- 01:19:40cancer is diagnosed at a later stage.
- 01:19:42But most cancers are still a diagnosis.
- 01:19:45Stage three and stage four,
- 01:19:47and the difference in survival
- 01:19:49between the woman who's diagnosed
- 01:19:51with stage one is life saving.
- 01:19:53You know somebody who's like those
- 01:19:55to stage one has 92 to 95% chance
- 01:19:57of survival versus only as low
- 01:19:59as 20% in advance stages.
- 01:20:01That is why it is so important for us
- 01:20:04to try to detect these cancers early,
- 01:20:07but more importantly, to try to prevent them.
- 01:20:11So part of the challenge.
- 01:20:12Are this limitation is that we have
- 01:20:14always been told we have always
- 01:20:16said there are varying cancer is
- 01:20:17a disease that whispers, you know,
- 01:20:19for generations we were told, you know,
- 01:20:21there's just nothing you can do.
- 01:20:22You can never find these cancers early.
- 01:20:24They are always like this.
- 01:20:26There's no symptoms until the disease
- 01:20:28and stage three and stage four,
- 01:20:30so there's really nothing that we as
- 01:20:32a field can do to make it better.
- 01:20:33But we know that it is very much
- 01:20:35not the case.
- 01:20:36We now know that ovarian cancer
- 01:20:39doesn't necessarily whisper,
- 01:20:40it's really that a lot of people
- 01:20:42are not listening to it.
- 01:20:44And that has to do with awareness
- 01:20:46on the patients
- 01:20:47patient sides.
- 01:20:48The vagueness of the symptoms,
- 01:20:50but also some limitations on
- 01:20:52the provider side as well.
- 01:20:55So some very good studies came out.
- 01:20:57This is one of the Seminole ones
- 01:20:59by Barbara Golf from Seattle that
- 01:21:01talked about that ovarian cancer
- 01:21:03presents with these specific symptoms,
- 01:21:05abdominal discomfort, GI discomfort,
- 01:21:07pain, constitutional, urine, pelvic,
- 01:21:09and even though great majority of
- 01:21:13them in stage three and four that
- 01:21:16that is 7% of patients in stage
- 01:21:18three and four had the symptoms,
- 01:21:2089% of women in stage one and
- 01:21:22two had those symptoms as well.
- 01:21:25And this study kind of debunked.
- 01:21:26This whole concept that we had.
- 01:21:28Talked about this so long before that the
- 01:21:31women in the early stage had no symptoms.
- 01:21:33Barbara Gold,
- 01:21:34they clearly kind of looked into
- 01:21:36who who are the patients who ended
- 01:21:39up having this ovarian cancer.
- 01:21:40Because, honestly,
- 01:21:41like any of us looking at the symptoms,
- 01:21:43it looks very concerning because all
- 01:21:45of us experience these symptoms and but
- 01:21:47she very much created this assessment.
- 01:21:49Risk assessment for women and for the
- 01:21:52women who actually had ovarian cancer.
- 01:21:54This woman had it consistently.
- 01:21:58Once every single day for two weeks
- 01:22:02compared to women who had them every
- 01:22:04two to two to three times per month,
- 01:22:07and often associated either with
- 01:22:10population or their menstrual cycles.
- 01:22:12Also,
- 01:22:13having more than one symptom
- 01:22:14was much more associated with
- 01:22:16ovarian cancer than those women.
- 01:22:18They just had hormonal changes,
- 01:22:20so this very much with Samuel study in this,
- 01:22:22I think gives us a voice and gives
- 01:22:24us the opportunity to educate our
- 01:22:26patients and educate communities about.
- 01:22:28Listening to your bodies and
- 01:22:30knowing when something is right.
- 01:22:31It's not right and not always
- 01:22:32just assuming that the symptoms
- 01:22:34you're experiencing a hormonal
- 01:22:36symptoms visible cyst.
- 01:22:37Symptoms are persistent and symptoms
- 01:22:40of multiple than you would need
- 01:22:43to be evaluated to rule this out.
- 01:22:46So as I mentioned 25,000 cases,
- 01:22:50a lot of deaths,
- 01:22:51most common cause of death by farm
- 01:22:55and with Joanne Cancer and 4th leading
- 01:22:58cause of cancer death in the United States.
- 01:23:02So to talk a little bit more about
- 01:23:04how these cancers can be prevented,
- 01:23:07which is really kind of the the
- 01:23:09motif that I want to talk about,
- 01:23:11is what can we do for prevention?
- 01:23:13I think it's important to understand
- 01:23:14who are the women who are at risk
- 01:23:16for epithelial ovarian cancers,
- 01:23:18which are the common ovarian cancers,
- 01:23:20so there's a couple of theories to this.
- 01:23:23There's actually two different theories,
- 01:23:25overbearing cancer.
- 01:23:26One the most common,
- 01:23:28and the oldest is this incessant ambulation.
- 01:23:32So the more times,
- 01:23:33the more that the women ambulates,
- 01:23:36the more risk she has on this tumorigenesis.
- 01:23:38Carcinogenesis so women who have
- 01:23:41had early monarchy, late menopause,
- 01:23:43who haven't had a lot of children
- 01:23:46who didn't breastfeed and who had
- 01:23:48infertility due to probably multiple issues,
- 01:23:51as well as did not use birth control pills,
- 01:23:54and the reasoning for this is
- 01:23:55similar that the more times that
- 01:23:57you're not ovulating,
- 01:23:58the less risk there is that
- 01:24:01this tabulation happened and.
- 01:24:02Precipitate some sort of
- 01:24:04a cancer development.
- 01:24:05The more recent thinking of again
- 01:24:09cancer Genesis is actually not that the
- 01:24:12cancer actually comes from the ovaries,
- 01:24:14but rather the cancer comes
- 01:24:16from the fallopian tubes,
- 01:24:17and we actually have a lot of thinking now,
- 01:24:19especially for women with hereditary
- 01:24:21germline cancers like a BRCA cancer,
- 01:24:25we very much believe that the origin of the
- 01:24:28disease is really in the fallopian tubes.
- 01:24:30Come here after being cancer.
- 01:24:33Genetic mutations,
- 01:24:34of course is the biggest risk factor
- 01:24:37predisposition to being cancer
- 01:24:39that is between brocco one bracket,
- 01:24:422 Lynch and now newly discovered
- 01:24:47additional genes.
- 01:24:48As I mentioned before,
- 01:24:49women with Brock one have as
- 01:24:51high as 46% chance of ovarian
- 01:24:53cancer as high as 23% in bracket.
- 01:24:56Two carriers with a lifetime risk in
- 01:24:59general population of 1.4 to 1.5%,
- 01:25:03so significantly increased incidence.
- 01:25:06Uhm?
- 01:25:09This is similar data that's shows that
- 01:25:11the risk of rock ovarian cancer with
- 01:25:14brocco one and bracket 2 gene mutation,
- 01:25:17both of breast and ovarian.
- 01:25:20So what can be done?
- 01:25:21What other factors that can reduce
- 01:25:23the risk of ovarian cancer?
- 01:25:25And there's some simple one.
- 01:25:26So multi parity really for the same
- 01:25:28reasoning that I gave you before that,
- 01:25:30the more the more that the woman is pregnant,
- 01:25:33the lashes ovulating.
- 01:25:34You have to have five children
- 01:25:37to decrease your risk by 50%.
- 01:25:40I have four children.
- 01:25:42I'm very close to the benefit and you
- 01:25:45have to breastfeed every single one
- 01:25:47for a year for additional benefit.
- 01:25:50One of one of the very big.
- 01:25:55Important points of chemoprevention
- 01:25:57in ovarian cancer is the use of oral
- 01:26:02contraceptives and that is something
- 01:26:03that I talk about excessively and
- 01:26:05use every opportunity to communicate
- 01:26:07this message because there's a
- 01:26:09lot of misinformation and lack
- 01:26:10of knowledge about use of oral
- 01:26:12contraception's in women.
- 01:26:13But we know due to that theory
- 01:26:16that I showed you before about the
- 01:26:19population that that increases risk
- 01:26:22that use of ocps birth control pills.
- 01:26:26Significantly decreases risk ovarian cancer.
- 01:26:29If a woman uses birth control pills
- 01:26:31for five years during her lifetime
- 01:26:33doesn't have to be at the same
- 01:26:35time could be just cumulative.
- 01:26:37It decreases her risk by 50% if
- 01:26:40she uses up a 10 or 15 years,
- 01:26:43it can include increase,
- 01:26:44decrease the risk by its highest 80 to 90%,
- 01:26:48and that risk reduction is not
- 01:26:50just for general population,
- 01:26:51it's also for women with BRCA mutations,
- 01:26:54so it will bear C1 mutation.
- 01:26:56Is a 40% chance of ovarian cancer
- 01:26:59and she uses birth control pills
- 01:27:01for five years that now reduces
- 01:27:03her risk to 20% and so forth.
- 01:27:07Tubal ligation, or even better,
- 01:27:09in this day and age,
- 01:27:10removal of the tubes is another
- 01:27:14very significant protective factor.
- 01:27:17It has relative risk of .3,
- 01:27:20so you can significantly reduce
- 01:27:22the risk by either tying the tubes,
- 01:27:24or even better, be moving it.
- 01:27:26And I think that is something that.
- 01:27:30Supports the theory that I talked
- 01:27:32about that the cancer might actually
- 01:27:34be coming from the fallopian tubes.
- 01:27:36You know, nowadays tubal ligation,
- 01:27:38really, it's a little bit old school,
- 01:27:39and I again thoroughly argued that
- 01:27:42if you're going to tie tubes,
- 01:27:44you should just remove them entirely,
- 01:27:45and anybody who's having hysterectomy
- 01:27:47for benign reasons should always
- 01:27:48have their fallopian tubes removed.
- 01:27:50I will never leave a fellow P2 behind
- 01:27:53because I very much see it as a very
- 01:27:56significant origin of carcinogenesis.
- 01:27:58And then of course, the most definitive one,
- 01:28:00but also reserved for the highest population,
- 01:28:03which is a risk reducing stopping
- 01:28:05over ectomy.
- 01:28:06Removal of both ovaries and tubes.
- 01:28:10Uhm, these are the relative risks I
- 01:28:13mentioned before umso breastfeeding.
- 01:28:16Really party infertility.
- 01:28:19Previous pregnancy ocps all
- 01:28:21those things I discussed.
- 01:28:23The only thing I didn't mention is the
- 01:28:26family history that even know somebody
- 01:28:28who does not have genetic mutation.
- 01:28:31Having relative with ovarian cancer and
- 01:28:33then compared to two or three relatives
- 01:28:36with a variant cancer significantly
- 01:28:39increases relative risk of developing it.
- 01:28:41So options for viewing
- 01:28:43cancer risk management.
- 01:28:44And yeah,
- 01:28:45you know,
- 01:28:46I always think of risk management pretty
- 01:28:48much the same for every cancer entity,
- 01:28:51so I same As for breast same As
- 01:28:53for pancreas enzymes for ovary.
- 01:28:55So the way I look at it as surveillance
- 01:28:58chemoprevention and again the most
- 01:29:00definitive but the one reserved for
- 01:29:02really the population at highest
- 01:29:04risk is prophylactic surgery.
- 01:29:06So here is the trouble.
- 01:29:07The trouble with. Start with the hardest.
- 01:29:12The trouble with surveillance in
- 01:29:14ovarian cancer is because unfortunately
- 01:29:16we do not have good modalities
- 01:29:19to detect these cancers early,
- 01:29:21and it's due for many different issues.
- 01:29:23I'm not going to bore you with
- 01:29:27the challenges of low PPD.
- 01:29:29And that you need 10% PvP in order
- 01:29:32to achieve this 10% PPV screening
- 01:29:35of general population must have
- 01:29:38very high specificity,
- 01:29:39which is almost impossible with these tests.
- 01:29:42So all our markers unfortunately have low
- 01:29:47specificity and also suboptimal sensitivity.
- 01:29:49Having to do with great deal with
- 01:29:52low prevalence in our population.
- 01:29:54That is why the two markers that
- 01:29:56we use for this are limited.
- 01:29:58You know,
- 01:29:59seeing 125.
- 01:29:59Is the one you probably hear the
- 01:30:02most about antigen expressed by fetal
- 01:30:05amniotic and coelomic epithelial?
- 01:30:07It's very complicated.
- 01:30:08It's super has has multiple false positives,
- 01:30:13multiple false negatives,
- 01:30:15many different entities like benign
- 01:30:17joint disease or GI disease increased at
- 01:30:21elevated significantly without malignancy.
- 01:30:24Other malignancies elevated and
- 01:30:26unfortunately in early stage like
- 01:30:28stage one disease great majority,
- 01:30:30a percentage of symmetry 5 is within
- 01:30:34normal limits and there's multiple
- 01:30:35different biomarkers that we.
- 01:30:37Looking at there's different ones somewhere.
- 01:30:39Actually good for specific subtypes
- 01:30:41of cancers.
- 01:30:42Others are not,
- 01:30:42and there's a lot of companies right now,
- 01:30:44and there's no research that's
- 01:30:46being done in the industry about
- 01:30:48trying to come up with different
- 01:30:50biomarkers to try to improve early
- 01:30:52detection and sensitivity.
- 01:30:53Specificity of the disease.
- 01:30:55There are other limitations.
- 01:30:57Ultrasounds also sound like now,
- 01:30:59so they're good entity.
- 01:31:00It's something that we really use,
- 01:31:01and it's really quite good, but again,
- 01:31:03just because of how the brain cancer
- 01:31:05is is found and how frequently
- 01:31:07it's in the Philippine tubes.
- 01:31:09The pie and specially its primary pet,
- 01:31:11Neil, and that even the ovaries,
- 01:31:13the ultrasounds again sadly
- 01:31:15frequently miss early disease.
- 01:31:18Miss Stage One, stage 2.
- 01:31:22The Ocps is what I talked about before,
- 01:31:25and this is the data that we have
- 01:31:27that shows great risk reduction in
- 01:31:30women who used birth control pills,
- 01:31:33especially over cumulative many years.
- 01:31:36And then the most definitive one would
- 01:31:38be a risk reduction with prophylactic.
- 01:31:40You know, I don't actually
- 01:31:41ever use the word prophylactic.
- 01:31:43I use the word risk reducing over
- 01:31:45ectomy in avoidant ovarian cancer.
- 01:31:48This is some of the older
- 01:31:49literature from our institution,
- 01:31:50from the computer Schwartz from here who
- 01:31:53published in those days in 94 that if all
- 01:31:58women had their ovaries removed at age 50,
- 01:32:03if they were having benign
- 01:32:05hysterectomy than 12%.
- 01:32:06Of women might avoid
- 01:32:08developing ovarian cancer.
- 01:32:09You know in that days in 94
- 01:32:11and probably 10 years ago,
- 01:32:13we kind of used to do it routinely.
- 01:32:14We used to take out ovaries routinely
- 01:32:17in this population of this age women,
- 01:32:19but now more studies are available
- 01:32:21and there's some good studies that
- 01:32:23show that there's possibly possibly
- 01:32:24and probably benefit to the ovaries.
- 01:32:26All the waves all the way to age 65.
- 01:32:29So now we are not as quick to take
- 01:32:32out ovaries in age 50 or so forth
- 01:32:34because we now have to balance.
- 01:32:36The risks and benefits,
- 01:32:38and this is again why it's so
- 01:32:40important to understand who is at risk,
- 01:32:42who has a high risk.
- 01:32:43So for those women you certainly
- 01:32:45would would want to remove their
- 01:32:47ovaries if you could.
- 01:32:49And then the prophylactic for
- 01:32:51bingo for ectomy in BRCA carriers.
- 01:32:53At this and the women,
- 01:32:54of course for the highest risk
- 01:32:56for this disease,
- 01:32:57multiple studies have been done.
- 01:32:59This is just one of them that
- 01:33:01showed that it significantly
- 01:33:04decreased risk ovarian cancer,
- 01:33:06and this study this women even
- 01:33:09after risk reducing over Ectomy
- 01:33:12had a 1.3% peritoneal cancer.
- 01:33:14That number is lower.
- 01:33:16Now we doing the surgery little bit
- 01:33:18more aggressively, a little bit.
- 01:33:20Medically we take a little bit more,
- 01:33:21but you know,
- 01:33:22I always counsel women that they
- 01:33:24probably have 1% chance of still
- 01:33:26develop development cardinal
- 01:33:27cancer even after the offer.
- 01:33:29Ectomy,
- 01:33:30but truly compared to you know
- 01:33:326% of this population.
- 01:33:34It's also very important to
- 01:33:36note that when the women remove
- 01:33:39their ovaries before menopause,
- 01:33:41it also reduces their risk
- 01:33:44of breast cancer by 50%.
- 01:33:46And it's also important to note
- 01:33:48that for these women in this.
- 01:33:50Providers who are young when we remove our,
- 01:33:53they're always.
- 01:33:54Not only is it acceptable or
- 01:33:56OK to put them on hormones,
- 01:33:59once you remove the always,
- 01:34:01it is actually proven and studied and not
- 01:34:04only is it imperative for their heart,
- 01:34:07their lot and their bones and their mood
- 01:34:09and their symptoms and their condition.
- 01:34:11But there's been studies that
- 01:34:13talked about safety in the breast
- 01:34:15cancer population that because
- 01:34:17women still have the 50% reduction.
- 01:34:20Of the breast cancer just from the
- 01:34:22offer ectomy that even the women
- 01:34:25who will put a very big dose in
- 01:34:27the study of hormones post be a so
- 01:34:29they did not have an increased risk of
- 01:34:32breast cancer after five and seven years.
- 01:34:35So that's actually a day ****
- 01:34:36point to know because that
- 01:34:38sometimes is something that's that.
- 01:34:41That's miss misconstrued it in
- 01:34:44the patient population that they
- 01:34:45worry they could not have hormones,
- 01:34:47and that's not at all the case.
- 01:34:49So in conclusion, ovarian cancer
- 01:34:51continues to be very challenging.
- 01:34:53Ovarian cancer continues to be
- 01:34:56very challenging because we are
- 01:34:58failing to diagnose it early.
- 01:35:00We are, and again not that the lack of Shank,
- 01:35:03not because we're not aware of it.
- 01:35:05It's more because we are so limited
- 01:35:08by the entities that we have
- 01:35:11for early detection between the
- 01:35:13ultrasounds and biomarkers,
- 01:35:14and because of that it is so important
- 01:35:17to understand who are the women at risk.
- 01:35:19So that their genetic
- 01:35:20mutations can be checked,
- 01:35:22and if they're truly at at increased risk,
- 01:35:24we can offer them surgical risk reduction.
- 01:35:27Nowadays we're doing a lot of risk
- 01:35:29reduction in younger women with just
- 01:35:31removing their fallopian tubes to
- 01:35:32support the theory that I mentioned
- 01:35:34to you before this cancer is coming
- 01:35:36from the Philippine tubes only.
- 01:35:37And there's a big trial that's
- 01:35:39going on right now,
- 01:35:39just looking at the risk reduction
- 01:35:42from fallopian tubes alone.
- 01:35:43But the key again is to understand who's
- 01:35:46risk and what can be done for this risk.
- 01:35:49Reduction and similar to the Farrell.
- 01:35:52I similarly have a practice where we
- 01:35:55have something called discovery to
- 01:35:57cure special practice where we take
- 01:36:00care of women at higher risk both with
- 01:36:04chemo prevention and surveillance.
- 01:36:07And then at most extreme times
- 01:36:09of high risk surgical prevention.
- 01:36:12Thank you so much for your attention.
- 01:36:19Great, thank you so much to
- 01:36:22all of our speakers tonight.
- 01:36:24There are a few questions in the chat
- 01:36:27but are in the Q&A but if anyone else
- 01:36:30has questions feel free to type them in.
- 01:36:32Doctor Farrell there was a question in
- 01:36:34there for you and I'll sort of paraphrase,
- 01:36:37but if a patient has a mutation
- 01:36:39that this associated with an
- 01:36:41increased risk for pancreatic cancer,
- 01:36:44should they automatically be referred to you,
- 01:36:46or is family history of factor
- 01:36:48in consideration of referral?
- 01:36:51So we do. We do follow the guidelines
- 01:36:54that are out there that are constantly
- 01:36:56being kind of revised and reviewed.
- 01:36:59But essentially it boils down to exactly.
- 01:37:08Essentially boils down to for most
- 01:37:09of the mutations that are out there,
- 01:37:11they do require a family history and
- 01:37:15the exceptions are P16 and put Jaegers.
- 01:37:19Uhm, there have been some discussions
- 01:37:21about opening it up so that we would
- 01:37:23end up surveying individuals with just
- 01:37:25those high risk germline mutations we
- 01:37:28talked about so bracket two probably
- 01:37:29to an ATM that isn't standard of
- 01:37:31care or followed any particular
- 01:37:33guidelines at this point in time.
- 01:37:35So so I would say that you know I
- 01:37:37think you have to realize there are.
- 01:37:39There are some German mutations
- 01:37:40that on their own are enough to
- 01:37:42justify surveillance but other
- 01:37:44ones require the family history.
- 01:37:45Having said all of that,
- 01:37:47there are times when we talk to patients.
- 01:37:49Who have incomplete family histories or
- 01:37:51they're still waiting For more information?
- 01:37:54So for those sorts of individuals,
- 01:37:55I just tell them to come into the clinic.
- 01:37:57We can talk.
- 01:37:58We can tease out other issues of
- 01:38:00pancreatic disease and the family,
- 01:38:01and kind of at least reassure them and
- 01:38:03give them answers to specific concerns
- 01:38:05they have about pancreatic disease.
- 01:38:07But the short answer is knowing
- 01:38:10which germline mutations required
- 01:38:12the family history is important.
- 01:38:16Great thank you and then Doctor Lynch.
- 01:38:18Uhm, there was some conversation.
- 01:38:21I think in the Q&A about whether
- 01:38:23or not to routinely include breast
- 01:38:25ultrasounds or whether or not that
- 01:38:27should really only be reserved for
- 01:38:29women with high risk or dense tissue.
- 01:38:32Would you like to comment on that? Sure.
- 01:38:37Am I muted now? Nope, you're fine,
- 01:38:41so supplemental screening is meant for
- 01:38:44women who have dense breasts where
- 01:38:46traditional mammography is not as sensitive.
- 01:38:49Supplemental screening can be with whole
- 01:38:52breast ultrasound or with breast MRI.
- 01:38:55Connecticut is unique in the
- 01:38:57country that the first dense breast
- 01:38:59legislation was passed in Connecticut,
- 01:39:01and immediately Connecticut
- 01:39:02radiologists jumped on using whole
- 01:39:05breast ultrasound for supplemental
- 01:39:07screening for those patients.
- 01:39:08And so there's a very.
- 01:39:10Deep clinical experience here
- 01:39:12with supplemental screening with
- 01:39:14whole breast ultrasound.
- 01:39:15Other parts of the country have moved
- 01:39:18more towards using breast MRI which
- 01:39:20is a much more costly and much less
- 01:39:22specific modality because they just
- 01:39:24don't have the clinical experience
- 01:39:27that you have at Connecticut.
- 01:39:29And so the whole breast ultrasound
- 01:39:31should only be used as a screening
- 01:39:33modality for women who have dense
- 01:39:35breast tissue or for or who are at
- 01:39:37increased risk for breast cancer.
- 01:39:41Alright, thank you so much.
- 01:39:43It doesn't look like we've
- 01:39:45received any more questions,
- 01:39:46so I think it will end for
- 01:39:48the night since it's late.
- 01:39:49Thank you all again for speaking
- 01:39:51with us tonight. Thank you.
- 01:39:54Thanks, Claire, thank you all. Thank you.