Smilow Shares: Breast Cancer Awareness and Treatment Advances with Trumbull and Fairfield

October 22, 2020

Information

Mehra Golshan, MD, MBA

Professor of Surgery (Oncology) and Interim Director of the Breast Center at Smilow Cancer Hospital

Neal Fishbach, MD

Assistant Professor of Clinical Medicine (Medical Oncology)

Melissa Mastroianni, MD

Assistant Professor of Surgery

Andrew Zhang, MD

Assistant Professor of Therapeutic Radiology

ID5807

To CiteDCA Citation Guide

00:00And undergoing mastectomy with
00:02Reconstruction and and cancer treatment.
00:04Then, doctor Andrew saying one of our
00:07senior radiation oncologists will be
00:10speaking on some of the advances and
00:12changes in radiation oncology and
00:15radiation treatment of breast cancer.
00:17And finally doctor Neil Fishback,
00:19who is well known to the community
00:22senior breast medical oncologist will
00:25be discussing many of the advances
00:27in Agimat therapy, so things like.
00:30Chemotherapy targeted therapy,
00:32and he may even have a few moments
00:35to talk about immunotherapy.
00:37So with no further ado,
00:39please welcome doctor Melissa Mastriani.
00:46Thanks everybody, give me one second.
00:49Alright can everybody hear me?
00:53Great so I'm Melissa Mastriani.
00:55I'm one of the new plastic
00:57and Reconstructive Surgeons,
00:58but I actually am fully boarded
01:00and general surgery as well,
01:01so I've learned the techniques of
01:03lumpectomy and Mastectomy as well.
01:05And I actually had the opportunity
01:06to train under Doctor Gulshan during
01:08my training years at the Brigham.
01:10So I'm really excited to join
01:12Yale and I'm so excited to bring
01:15my visions to everybody here.
01:17So I want to start out with with just
01:20discussing breasts as as an organ.
01:22It's not just in organ,
01:24it's not a Gallbladder that
01:26you can just remove.
01:28It's really important part of female
01:30sexuality and the feminine image as we
01:32can see dating back into Renaissance
01:34paintings and French impressionism.
01:36Beyond that it the breasts make
01:38milk to nourish babies and they
01:40grow and change with the woman.
01:43So as you can see in all
01:45these artists portrayals,
01:46these are very youthful breasts.
01:48They are lifted and their happy.
01:50There were, they should be on the chest,
01:53but as we age,
01:54that's not always how they appear.
01:57In addition,
01:57you any woman may have noticed
01:59that breasts are sisters,
02:01but not Twins.
02:02There are always some anatomic asymmetry's
02:04in breasts that we always like to point out
02:06to women before they undergo reconstruction,
02:09because it's important to know
02:10the differences in your breasts.
02:12And it's also important to know that
02:14everybody has differences in their breasts.
02:16They're not going to be
02:18mirror images of each other,
02:20so nor can.
02:21We expect that in our reconstruction.
02:24So if you're looking at your
02:26breasts in the mirror,
02:27you should know that they shouldn't
02:29change significantly after puberty
02:30except during pregnancy and postpartum,
02:32and were lack tating and feeding
02:34babies and serving one of the
02:36physiologic purposes for breasts.
02:37But ultimately you should not notice
02:40major changes in your breasts after
02:42you undergo puberty and develop them.
02:45I I saw this on Facebook and one of my
02:48colleagues website San it's you know
02:50how to know what cancer feels like.
02:53But this isn't just cancer.
02:55This is also banite breast disease.
02:57You may have a Mass in your breast,
03:00but it could still be round an normal.
03:03It could be a fiber adenoma
03:05which could be completely benign.
03:07But if you know your breasts at baseline,
03:10you can understand when something
03:12like this is changing.
03:13So if you identify an indentation.
03:15Or in Errosion,
03:16or a change in your breast appearance.
03:18This is really important to
03:21talk to your doctor about.
03:23Breast cancer is one of the most
03:25common cancer affecting American
03:27women in the United States.
03:29One in eight women in their lifetime,
03:31that's 13% will get breast cancer.
03:33So chances are that you know
03:35somebody who has breast cancer or
03:37who may develop breast cancer.
03:39'cause This is a lifetime risk.
03:42Signs of cancer,
03:43meaning you may notice a lump in the breast.
03:46It's usually not painful,
03:47but it's going to feel like
03:49a lemon seed. It's going to be firm.
03:51It's going to have irregular edges
03:53and it's not going to be nice
03:55and well and rounded and soft.
03:56You may notice some swelling or skin
03:58texture change or a change in your nipple
04:00that made instead of poking outward.
04:02It may poke inward.
04:03You may notice some drainage
04:05and all that is not normal.
04:07If you know your breasts then
04:08then if something is different,
04:10bring it up to your doctor and
04:12we also recommend mammograms.
04:13Everyone to two years starting at age 40.
04:16If you have a strong family history,
04:18usually we recommend those
04:20mammograms starting even earlier.
04:22To reduce your risk,
04:24just basic broad strokes.
04:25Women are recommended to drink less than
04:28one or less than two drinks per day.
04:31If we are drinking more than
04:34two drinks per day,
04:35that increases our risk more than
04:3820% for not just breast cancer,
04:40but any cancers.
04:41It's important to maintain a healthy
04:45weight and also be active and have.
04:48Good activity levels in a day.
04:50Getting our heart rates up very important.
04:52The other things that we talk about are
04:54birth control and even hormone replacement,
04:57but this is not all birth control
04:59and not all hormone replacement.
05:01And it's important to determine the
05:03length that you're going to be on them in.
05:06Finally I found this very interesting,
05:08but apparently there are some myths out
05:10there that deodorants in certain bras
05:12have been linked to breast cancer risk.
05:15So all of those have been debunked.
05:17You can wear deodorant.
05:18You can wear your bras like normal
05:20and then that is going to increase or
05:23decrease your risk of breast cancer.
05:25So if you are unfortunate to develop breast
05:28cancer or even a benign breast disease,
05:30we often treat this with a team approach.
05:34This involves surgical teams,
05:35which is not only me as a plastic surgeon
05:39but also an oncology surgeon who will
05:41be in charge of removing the lumps,
05:44making sure that your lymph nodes are
05:46clear and that everything is removed
05:49that might be cancerous to you.
05:51Sometimes that involves chemotherapy and
05:53radiation, so we all like to talk about this.
05:57Together.
05:57We have a basic team.
05:59Approaching,
05:59we actually talk about very complicated
06:02caitians on a weekly basis to find out
06:04what the best way to treat patients is.
06:06So the surgical treatments,
06:08because I'm a surgeon,
06:09would involve taking the lump or the
06:10mass out and we call that a lumpectomy.
06:13And literally,
06:13we scoop out the lump.
06:15But it has to have a rim of normal
06:17tissues that we can make sure that
06:19we get all the cancer cells out in.
06:21This involves the little roots that may grow,
06:23and it's important to have that normal
06:25rim of tissues to make sure that we
06:28get all of those cancer cells out.
06:30If this is not an option for you,
06:32you may require a mastectomy ning
06:34meaning you have to remove the
06:36entire breast gland in and of itself,
06:38and both of those are fine if you
06:41need that for cancer resection.
06:43Here is a huge diagram of all of the
06:46possible iterations of breast surgery
06:48that you can undergo to remove your mass.
06:51If you need a lumpectomy
06:52and you have large breasts,
06:54we have lots of different ways to
06:57conceal the lumpectomy and to even have
06:59a matching procedure on the other side.
07:01So that doesn't mean that you
07:03necessarily have to have a mastectomy.
07:05And then on the right side of your screen,
07:08there's a number of different ways that
07:11we can perform the mastectomies such that
07:13you would have a reasonable outcome.
07:15In a reasonable reconstruction to
07:17give you a normal appearing breast,
07:19you notice a lot of these involve the nipple.
07:21Sometimes we have to remove the nipple
07:23to be safe as far as respecting
07:25enough cancer tissue,
07:26we don't want you to have to
07:28worry about recurrent cancer,
07:30especially after undergoing
07:31what you're going through.
07:33So the basic tenants of
07:34breast reconstruction,
07:35we can either reconstruct with
07:37an implant meaning something
07:38that is foreign to the body,
07:39but we put it in the body,
07:41so we need to make sure that everything
07:43is nice and clean and sterile,
07:45and it gives a very nice result
07:47at the top of the screen.
07:49That's an example of a tissue expander,
07:51so if you have small breasts and
07:53need to undergo a mastectomy when you
07:55would like to have bigger breasts,
07:57or maybe need to undergo radiation,
07:58this is a good temporary measure,
08:00and then we can exchange it down
08:02the road for a permanent implant
08:04which you can see at the lower ends.
08:06Of the screen here,
08:07the one in the middle is a shaped
08:09implant and it has texture because
08:12you wouldn't really want that
08:13flipping around and you need to have
08:16that texture like a Velcro so that
08:18the implant stays in its place and
08:20assumes in just basically becomes
08:22part of your body so that you didn't
08:24want to wake up one morning and
08:26have the top end up at the bottom.
08:29It would be very disfiguring for
08:31you and then the bottom implant is
08:33a smooth round gel implant which
08:35is very very versatyle.
08:36It can spin around, it,
08:38can flip around and you really not
08:40going to know much of a difference.
08:42The other option in reconstruction,
08:43which is,
08:44I guess new word but not entirely new,
08:46is using your own tissue in reconstruction.
08:50So I wanted to show you basically if
08:52you think about breast implants you
08:54think about people getting augmentation.
08:56You know getting breast implants
08:58for being more voluptuous and in
09:00more of an aesthetic appeal,
09:01and on the right diagram you can see that
09:04usually we put them under the gland tissue,
09:07but in reconstruction it's more
09:08difficult because we don't have a gland.
09:11The breast gland to really hide those
09:13contours of the breast implants,
09:15we have to have a Fuller implant
09:17to fill in
09:18the tissue, and in this skin flaps.
09:21To make a good,
09:22reasonable appearing breast,
09:23so here's a brief example of
09:26what a really good breast implant
09:29reconstruction outcome can look like.
09:32But despite the many types of shapes
09:34and sizes and fills of breast implants,
09:37there really isn't.
09:38A1 size fits all for everybody.
09:40You know we can go all the way to
09:43shaped implants and do our best,
09:45but ultimately it's really hard
09:47to imagine natural looking breast
09:49despite all of the technology we have,
09:51we still can't always get it right.
09:54So for patients who are not candidates
09:56for breast reconstruction with an implant,
09:58or maybe have been radiated.
10:00And who have limited options,
10:02I oftentimes offer patients
10:03using their own tissue,
10:05and these are a number of different
10:07areas that we can harvest tissue from to
10:10reconstruct a realistic feeling breast.
10:12This is your own tissue.
10:13You don't have to take immunosuppression.
10:15The most common area that we
10:17harvest from is the abdomen,
10:19so you essentially get a tummy
10:21tuck for free out of this,
10:23but it's really great tissue.
10:25It feels completely natural and we
10:27can give you a very realistic result.
10:30If that's not an option.
10:31Sometimes we can use the inner thigh,
10:33the upper buttock, or even the back.
10:37And this is an example of a unilateral
10:39reconstruction with that abdominal tissue,
10:40and you can see we do a pretty
10:42good job of matching,
10:43but you still are lacking in
10:45that nipple reconstruction.
10:46So for a lot of women,
10:48having a nipple really makes the
10:50reconstructions that they don't have to
10:51wake up and look at scars every day.
10:53And that's very important for a
10:55lot of people in their image.
10:57But as you can see,
10:58we can give a very natural looking
11:00appearance with their own tissue.
11:01You never have to worry about
11:03having an implant you don't have
11:05to worry about surveillance.
11:06And you can see the scars are actually
11:09pretty tolerable for this operation.
11:12So then we follow on to nipple
11:14reconstruction and on the left we see
11:16a couple of different ways that I
11:18can actually reconstruct projecting nipple.
11:20But this doesn't always include
11:22the pigment changes,
11:23so I wanted to include on the far right
11:25of the slide is actually somebody
11:27I just met who does 3 dimensional tattooing,
11:30so that is not 3 dimensional.
11:32That is completely flat.
11:34She can tattoo these results so
11:36even if you don't want to have a
11:38projecting nipple you can have a
11:40very realistic appearance of a
11:42nipple in a nipple areola complex without.
11:44Necessarily undergoing additional procedures,
11:45and it will completely natural.
11:47You can feel more whole and it
11:49will conceal your mastectomy scars.
11:51So I wanted to share these options as.
11:55Newer things on the on the.
11:59On the pipeline,
12:00kind of coming up for reconstruction,
12:02but also to consider some older
12:04techniques like tattooing.
12:05Even that would be certainly
12:07appropriate and reasonable to offer
12:08anybody who's undergone mastectomies
12:10or reconstruction,
12:11and they can make people feel whole
12:13again at the end of all of this.
12:16All their cancer treatments.
12:17And once there, once they are
12:19beyond the worry about survival.
12:21So I really enjoy helping people feel whole.
12:23I talked to people through the whole journey.
12:26I see them very frequently through
12:28the first year of reconstruction.
12:30And I always let them know that
12:32this is not necessarily a one
12:34stop shop and I can't take care
12:36of everything in one operation,
12:38even though I would love to have
12:40them wake up and feel completely
12:42whole again with their breasts.
12:44But I really try to get to know
12:46my patients and help them through
12:48that first year journey to get
12:50to their final reconstruction.
12:52So I'd be happy to take questions at the end,
12:55but I just wanted to give a
12:57brief overview of what
12:58I can offer. This is really fantastic.
13:00Doctor Mastriani and I know this
13:02is going to lead to a lot of great
13:05questions later this evening.
13:06I see Doctor Fishback has joined us,
13:09but since I've changed the order now three
13:12times and maybe will have doctor Zang
13:15go next and then the cleanup batter is
13:18doctor Fishback, right on?
13:19Thanks Mara, thanks. I Melissa,
13:21let me share my screen here.
13:29Go front.
13:35OK, my name is Andrew saying I'm
13:37one of the radiation oncologist.
13:39It's a true pleasure to be here and share
13:42a little bit about tremble Cancer Center,
13:45which is one of seven cancer
13:47centers here and yeah.
13:48So without further due this year on the
13:51topics will hit them quite briefly.
13:53But there's five topics.
13:54First is just a general site overview.
13:57What does art rumble?
13:58Cancer Center have?
13:59An #2 is general breast treatment
14:01options for radiation therapy actually
14:03follows Melissa's talk very nicely,
14:05because radiation is usually
14:07given after surgery.
14:08And #3, how does radiation work?
14:10I hope it does because we give it a lot.
14:14#4 is advances in our radiation
14:16delivery and #5 is advances in the
14:18treatment techniques which is really
14:20interesting and can't wait to get there.
14:23So let's let's start by #1.
14:26So our Cancer Center has
14:28the technical aspect.
14:29Our machines.
14:30We have two linear accelerators that
14:32called Linux the machines on the for
14:34example on the right that produced
14:36the radiation treatment photons.
14:39Electrons are all options from
14:41these machines and then we have a
14:43dedicated CT machine we call the see
14:46T simulator to help identify the.
14:48For example, the tumor cavity,
14:50the brass, the heart,
14:52lungs and treat to millimeter accuracy.
14:54So that allows us to.
14:57Plan our radiation according to your anatomy.
15:00Where patients anatomy.
15:01So we have Staffs.
15:03Two radiation colleges hunt side.
15:05We have a whole team of dosimetry,
15:08physics therapists nursing PA.
15:09So radiation is just not one physician
15:12ministering the treatment but actually
15:14takes entire team to deliver a safe
15:17and effective radiation therapy plan.
15:21So surgery systemic therapy,
15:22which Neil will talk about radiation,
15:25we all work in conjunction
15:27after a surgical procedure.
15:29Whether it's a lumpectomy, may,
15:31or whether it's miss activate their
15:34options for radiation treatment,
15:35after a lumpectomy.
15:37Usually we get whole breast
15:40radiation treatment. BRT.
15:41After masectomy it's postmastectomy
15:43radiation and each one of those
15:46we can add in regional notes.
15:48If a patient is high risks,
15:51for example with very large
15:52aggressive invasive cancers
15:54or their nodes are positive.
15:59The treatment given with radiation has
16:01changed over the past few decades.
16:03Traditionally, all patients have gone
16:0550 Gray in 25 fractions radiations
16:07given Monday to Friday every single day.
16:10So that's five days a week,
16:12leading to five weeks.
16:14So over the past few years,
16:16we've been uniformly throughout
16:18the country and actually pretty
16:20much throughout the entire world,
16:22going to hypo fractionated course.
16:23That basically means we take
16:26that 15 to 5 week.
16:2850 Gray treatment, and we condense it.
16:30So instead of two great day,
16:33we actually increase it a little
16:35bit to maybe 2.6 great day.
16:37And that only takes 15 treatments.
16:39Three weeks after the whole breast radiation.
16:42These are more than conventional
16:44approaches we can boost,
16:45and the boost is basically the
16:48last week of treatment added
16:50on to the five or three weeks,
16:52and we either target the
16:54lumpectomy cavity itself,
16:55which is the higher this re occurrence,
16:58or retire.
16:58Get the postmastectomy scar line
17:00that is usually given over a
17:02course of four or five fractions,
17:04and that's added on to the five
17:06or three weeks.
17:11So what is whole breast radiation?
17:13Well, as you can see in the diagram
17:15on the right patients lie supine,
17:17belly up with their arms up and our machine
17:20is able to deliver these tangent beams
17:23that only really target the breasts in
17:25this case and spare the normal tissue.
17:27So if you can see my mouse here,
17:30I'm going to point out the
17:32radiation treatment field.
17:33So let's say this machine head is over here.
17:36It's giving a medial treatment tangent so it.
17:39It's the breast and avoids normal tissue
17:41like the lung, so this black is the lung.
17:44This is the heart and the dose
17:46here in this multi colored region
17:47is the vast majority of the dose
17:50which targets the breast.
17:55This can also be given either
17:57supine like I described or prone,
17:59belly douse, Owens belly down.
18:01There is a board that looks like this,
18:03and a patient lies with belly
18:05down and a breast hangs down.
18:07This technique is really
18:08good for women with large,
18:10pendulous breasts because as you
18:11can see it separates the breast from
18:14the chest wall and by definition
18:15also from the internal organs like
18:17the heart here circled in purple.
18:19So when the breast falls into this
18:21cavity here we can target it with very.
18:24Similar arrangement of things and
18:26spare the heart and the lungs.
18:29Which are these black spots
18:32from radiation treatment?
18:34As I mentioned,
18:35whole breast radiation or
18:36postmastectomy radiation can also
18:37include regional lymph nodes.
18:39So what are these regional lymph nodes?
18:41Well they exist kind of in
18:43the border of the breast.
18:45So here we have the breast.
18:47Here we have the internal
18:49mammary lymph nodes.
18:50We have axillary lymph nodes.
18:51We have super clavicular lymph nodes.
18:53All these lymph nodes kind of
18:55drained fluid from the breast.
18:57And if the primary tumor unfortunately
18:59goes when the lymph nodes, well,
19:01it generally it's one of these.
19:04So how do we treat that with radiation?
19:06Well,
19:07here we have a patient that is
19:09getting postmastectomy radiation.
19:10So they had mastectomy and
19:12actually an implant.
19:13Here you can see this nice circular
19:15over feature we treat with similar beam.
19:18So the red beam is that medial
19:20tangent I described previously.
19:21The blue comes from the other side
19:23to give a very homogeneous dose,
19:26and the orange being is from the top.
19:29Which treats the Super clavicular
19:31look Jones up here if you can see
19:33this little purple circle here,
19:35that's the internal mammary lymph
19:36nodes that actually is treated
19:38with the tangent beams as well.
19:39So not only do we treat the
19:41chest wall in this case,
19:43but we also treat the regional lymph nodes,
19:45which is very important many patients.
19:49So the next topic is does radiation work?
19:51Now there's many, many different studies.
19:53If I just want to bring this one study,
19:56I suppose is a meta analysis with
19:58the largest number of patients.
19:59So let's kind.
20:00Just look at this one graph here.
20:03So over 10,000 patients,
20:0417 trials,
20:05all of these patients had lumpectomy's
20:08breast conservation surgery and
20:09whole breast radiation an all
20:11comers at the five year interval.
20:13Without radiation,
20:14the re occurrence rate,
20:15any first re occurrence is 25%
20:18which is decreased by half.
20:20So this is kind of an with other studies.
20:23This is kind of where we get the I
20:26supposed mantra that radiation decreases.
20:29Local regional recurrence by at least 50%.
20:36Here we have patience with
20:38node negative disease.
20:39In here we have patients with node
20:42positive disease and it makes a very
20:44big difference whether or not they
20:47had node positive or no negative,
20:49and this study kind of concluded.
20:51Another thing that we often think
20:54about is how many reoccurrences
20:55can we avoid in order to prevent 1
20:59deaths and based on this one study,
21:01it's every four reoccurrences avoided
21:03equals one breast cancer death.
21:05Avoid it so a four to one ratio is
21:08kind of the name of the game in
21:10terms of whole breast radiation
21:12and preventing these outcomes.
21:17And as postmastectomy radiation works,
21:18you bet and lymph nodes also matter here.
21:21So this is actually really interesting
21:23because the lymph nodes matter a lot more
21:26in terms of postmastectomy radiation.
21:28If you are lymph node negative,
21:30these 700 patients radiation really
21:32doesn't make a difference and we often
21:34don't do post secondary radiation.
21:36These very small cancers,
21:37for example there are linked to negative.
21:40But if your lymph node positive then
21:42it does make a tremendous difference.
21:44Here at 10 years without radiation,
21:4626% of local regional reoccurrences.
21:48And with radiation it's 8%,
21:50so it is a pretty big significant difference.
21:57We have some advances in radiation.
22:00One of the advances in order to
22:02decrease side effect is this
22:04advancement called surface image.
22:06It's a technique where using different
22:08light fields were able to construct a
22:113D representation of your chest wall.
22:13So here on the right you can kind
22:15of see this 3D representation.
22:18This is important because it measures
22:20the rise and fall of your chest wall,
22:23so these are continuous during treatment.
22:25The radiation treatment itself is
22:27in the matter of seconds, actually,
22:29that is when the radiation beam
22:31is actually being delivered.
22:33So a lot of times what happens
22:36is during radiation.
22:37We want to do two things who want to check
22:40the accuracy of the patients treatment.
22:42So you can imagine since radiation is
22:44either three weeks long or five weeks long,
22:46we want to make sure that patients in
22:48the exact same position every single day.
22:50The worst thing that could happen is
22:52one data positions off in here and then
22:55we missed the whole breast with a chest wall.
22:57In order to avoid that we have different
22:59techniques like this in order to
23:01measure the patient chest wall and
23:02position the patient correctly #2.
23:04Not only do we want the patient
23:06to be the same.
23:07Every day,
23:08but during the treatment itself we
23:09have to monitor the patient just in
23:11case there is some unknown movement.
23:13For example,
23:14the patient has a terrible see is who
23:17they cough or they move during treatment.
23:19So this is called gated treatment.
23:21Attracts changes in position and location
23:23during the actual treatment itself.
23:28With that technique,
23:29were able to monitor the patient
23:31breath and the technique that we use
23:33is called deep inspiration breath hold
23:35so this technique can be best shown
23:37in these two images here on the left
23:39and the right is the same patient,
23:41but here on the left the patient
23:43is just breathing normally we have
23:45a chest CT scan of the chest.
23:47Here's a breast up here.
23:49Here's a heart and pink,
23:50but if the patient takes a breath
23:52you can see the lungs are expanded.
23:55The heart is moved away from the breast.
23:57And therefore the heart will get less dose,
23:59which is exactly what we want
24:01in these plants.
24:04I drew a red line here to
24:06show the beams of radiation.
24:08The posterior border of the beams.
24:10As you can remember,
24:11there's a medial tangent.
24:13There's a lateral tangent and
24:14that theme edge is represented
24:16by the red without breath hold.
24:18Sometimes it's very difficult to
24:19avoid a heart, as you can see here,
24:22there's some little overlap
24:23which we don't want,
24:24but with Breathhold were
24:26able to avoid the hard,
24:27sometimes entirely,
24:28and that decreases our long-term
24:30side effects for the heart.
24:35So this is another representation
24:37of how the heart moves with
24:39the breath hold technique.
24:41The Red is the heart here.
24:43The Green is the diaphragm.
24:44So if you take a breath in the heart
24:47moves it down an moves backwards,
24:50so those two movements really help
24:52prevent radiation dose to the heart.
24:58This is what the patient sees actually,
25:00so the patient wears these funky
25:01goggles and on the goggles there's
25:03this little bar thing here.
25:05This orange bar moves up and down to the
25:08patients breath and this is what we see.
25:10So when the patient just breathe
25:12normally up and down, up and down,
25:14up and down until we take tell the
25:16patient to please hold your breath into
25:19the green line and so they hold their
25:21breath into the Green Line and hold
25:24it during the duration of treatment.
25:25Which is usually in the order of.
25:28I would say 15 seconds or so.
25:30The patients green lines hear
25:31what they see is this bar,
25:33so all they do is that they make sure
25:35they hold their breath within the line.
25:3815 seconds.
25:38Usually most patients can do this
25:40without any problems at all.
25:44So there are new treatment
25:45techniques that we have been
25:47following and adapting here at Yale,
25:49and they're actually really,
25:50really interesting.
25:51So I want to share a few of them with you.
25:54So as you know,
25:56the traditional treatment like I
25:57mentioned was five weeks, 25 treatments.
25:59It's very long and the question is,
26:01what if we can always shrink it?
26:04So over the course of the past few decades,
26:07we've shrunk it from 5 weeks.
26:09That three weeks there's a lot of
26:11data here in Europe or whatnot.
26:13That is, further shrinking that,
26:14so this is called the fast regimen.
26:17What if we can do breast radiation,
26:19whole breast radiation in five treatments,
26:21not five weeks?
26:22And when that be amazing to
26:23the patient to save time,
26:25and if it has the same
26:27efficacy and side effects,
26:28and that would be a very good
26:31alternative to some patients.
26:32So it turns out that based on data that
26:35that has become a reality in the past
26:38few years and now in most of our centers,
26:42we're offering this fast regimen,
26:43which is a five treatment course once
26:46a week for early stage patients.
26:48These are not the node positive patients
26:50that require the regional nodal radiation,
26:52but they just require whole breast
26:54radiation after a simple lumpectomy swear,
26:57something small like a,
26:58for example 1 centimeter small breast cancer.
27:01So right early stage,
27:02no negative after lumpectomy.
27:03These are generally the patients
27:06that we want to.
27:07Treat with this regiment.
27:09Now another regiment that we have been
27:12discussing is you can imagine well now
27:14if a cancer is 1 centimeters in size.
27:17Do you have to treat the entire breast?
27:20A lot of patients asked me
27:22that and I always say that,
27:24well,
27:25maybe not so this is called
27:27accelerated partial breast radiation.
27:28Truly actually has been around for a very,
27:31very long time,
27:32but the techniques have been changing.
27:34This one technique is actually from a
27:37center in Italy that reported the study.
27:40Showing a also a 5 fraction treatment
27:42every other day to part of the breast,
27:45hence accelerated partial breast.
27:46This currently is our operating
27:48procedure and our safety
27:49procedures currently in the works.
27:51So maybe if you were to ask me in a
27:54month or two or maybe three months,
27:57we'll see if we can get this up and running.
28:00So this is something in the future
28:02that we're looking forward to as well
28:05so we have all these different new
28:07options in order to help the patients offer.
28:10Different treatments according
28:11to the patient's busy schedules
28:13and to deliver safe radiation.
28:20Not only do we have new treatments,
28:22but we are a center that really believes
28:25in pushing medicine to the cutting edge
28:27and a lot of the cutting edge treatments
28:29have to do with clinical trials.
28:32These are large, randomized, often
28:33randomized trials that asked the question.
28:35While we have this standard
28:37treatment that's very, very good,
28:39but we have data showing that you know
28:41other treatment can be just as good,
28:44maybe even better.
28:45Why don't we do a study randomizing
28:47patient between one or two arms?
28:49And see what the outcomes are.
28:52So based on earlier studies like I mentioned,
28:55this one study is called the fabric trial,
28:57which is fractionation after
28:59breast reconstruction.
28:59So if you remember the picture I showed
29:02before with implantation to 1, not there,
29:04then anatomy of the implantation,
29:06it's a little different than normal tissue,
29:09but not by much.
29:10But we want to make sure that it's safe,
29:13so this is a really good trial in order
29:16to show if the standard treatment,
29:18which is the 25 fractions to 50 Gray
29:21is the same as the 16 fractions.
29:23242 Gray some centers do 15 fractions
29:26some centers, 216 fractions,
29:28but this one trial does the 16 fractions.
29:31Now what is the outcome that
29:33we're looking at?
29:35It is the patient report outcomes.
29:37Basically that's caused me sis.
29:40Radiation, as you might know,
29:42is like kind of like the sun.
29:44You get the sunburn on the breast,
29:46and that's a major side effect,
29:47so it's little red,
29:48itchy peely they'll tan,
29:49and that is what we are looking
29:51at to see if these two fractions
29:53are the same or one is better.
29:58The final the final study.
30:00I want to bring to light is
30:03something called Deescalation?
30:04What if we're giving too much
30:06radiation or to such a large area
30:08that a lot of patients don't need it?
30:10Surely there are grey zones and
30:12radiation like any other specialty.
30:14Sometimes these grey zones
30:15have to do with lymph nodes.
30:17In this particular case,
30:19the patient had low volume lymph nodes
30:21and I mentioned that before lymph
30:23nodes are almost always indicator
30:24to treat the regional lymph nodes.
30:26Well, not necessarily because
30:28certain times there are Gray area.
30:30So we want to see.
30:32In patients with lumpectomy,
30:33if they can randomize him,
30:35the whole breast radiation or radiation
30:37and regional locales in the second patients,
30:39we don't have to do post inspecting
30:42radiation or postmastectomy radiation.
30:4311 notes.
30:44Basically,
30:44this is just to show that,
30:46again,
30:47we're trying to push the boundaries
30:49and understand these Gray
30:51areas better so we can tailor
30:53deliver radiation treatment to
30:54the patients that we deem that
30:56they need extra treatments.
30:57For example,
30:58it actually treatment would be
31:00the regional nodal radiation.
31:04So in summary, radiation is an essential part
31:06of multi daldy treatment of breast cancer.
31:09It is very important and works
31:11just hand in hand with surgery,
31:14systemic therapies and radiation clearly
31:16does work and it decreases the risk
31:19of tumor recurrence by at least 50% in
31:21most cases of whole breast radiation,
31:24radiation can increase patient
31:25survival and select subsets and
31:27a lot of these are node positive,
31:30patient that we treat with posting
31:32secondary radiation to prevent.
31:34Reoccurrences and advances in radiation
31:36have improved side effect profile.
31:38That is, the deep inspiration,
31:39breath hold and the techniques to protect
31:43the patient from dose to the lung and heart.
31:47Finally, clinical trials and new
31:48treatment options are available on
31:50most of our radiation oncology sites,
31:52and that's great because you want
31:54to push the boundaries and also
31:56deliver tailor make ready issue
31:58now here are all the centers that
32:00we are currently operating in.
32:02We span from Greenwich here to New London.
32:05Here our main satellites.
32:06The One I work at here is Trumbull,
32:09but the main salads are all here.
32:11Listed below are smile,
32:13Cancer Center,
32:13New Haven of course is the mother ship.
32:17And whatever you get radiation treatments,
32:19we all have chart rounds on Wednesday,
32:22so all the breast radiation colleges get
32:25together and kind of look at this plant.
32:28So the treatment from any of the
32:30centers is pretty much pretty
32:32identical because we all look at the
32:35plans in order to deliver the best
32:38radiation treatment for patients.
32:39And I think that's it.
32:41In like most of said,
32:43will answer questions at the end.
32:46Andrew, that was terrific and that
32:48last slide, even though those
32:50circles were sitting over the Long
32:52Island Sound radiation stuff.
32:58And finally, we're going
33:00to move to doctor Fishback.
33:01Last but not least,
33:03to talk about some of it really.
33:05Some fantastic changes in the world
33:07of medical oncology and drug therapy.
33:09And again, I'm encouraging those
33:11that are listening in to put in
33:14through the question and answer
33:15and and chat any questions so
33:18we can start preparing those.
33:19Thanks Neil.
33:20Alright, thanks for.
33:21Let me see if I can.
33:24Share my screen here.
33:38How am I doing? Am I can
33:40people see my screen?
33:44Mirror Yep, Yep you did.
33:46It was so you were able to see it.
33:50OK cool alright so two things I have
33:53learned from doing events similar to this
33:55one from Project Runway fashion show.
33:58Never walk down a runway after a fireman
34:00and the second from these informational
34:03sessions is never go after a plastic
34:06surgeon or radiation oncologist 'cause
34:08their pictures are always much cooler
34:11than the medical oncology pictures.
34:13So I apologize that the photos
34:15may not be overly inspiring.
34:17But the information is certainly yes,
34:19so we're going to talk about the medical
34:23oncologists perspective to what's new
34:25in breast cancer over the last year.
34:27And we're just going to touch on
34:30three topics that will cover how are
34:32we improving preventing recurrence
34:34of breast cancer after tumors
34:36been removed from a breast?
34:38And specifically,
34:39we're going to talk about a drug abemaciclib,
34:42which is recently been demonstrated to have
34:45a significant impact in reducing risk of.
34:48Estrogen dependent breast cancer recurrence.
34:49We're going to talk about a tool
34:52called the breast cancer index,
34:54which is helping us make decisions
34:56about what's the best duration of anti
34:59estrogen therapy 5 or 10 years and we're
35:02going to talk about a newcomer drug,
35:04sassy to some app,
35:06which recently was FDA approved.
35:08To treat women with breast cancer that is,
35:11come back or spread a specific subtype.
35:13Triple negative breast cancer,
35:15but one.
35:15We're very excited.
35:16May be applicable to the whole spectrum
35:19of women with metastatic breast cancer,
35:21and as we touch on each
35:23of these three topics,
35:24we'll also highlight how we're trying to
35:27answer the next generation of questions
35:30at Yale through clinical trials.
35:32So first some nomenclature things,
35:34your definitions,
35:35things your breast team may be saying
35:37that may sound sort of familiar by choice.
35:40Wonder what they meant.
35:42So when we use the term ajibon therapy,
35:45we're really talking about treatments
35:47that are given after a primary tumor
35:49is removed from the breast with the
35:52goal of preventing recurrence in
35:54both the breast in a distant site.
35:56So very much like after you might
35:58pluck a dandelion from your yard.
36:01If you don't like.
36:02Dandelions and don't want any
36:04to crop up anywhere else.
36:07You may apply dandelion control
36:09to the entire lawn,
36:10not just for the Dandelion was that's
36:13the idea behind agement therapy
36:15and that can come in many forms.
36:18Chemotherapy,
36:18anti estrogen treatments or increasingly
36:21targeted therapies and when we get to
36:24talk about abama cycling been a second.
36:26That is a relatively new pathway.
36:28Acd K46 Pathway which we'll delve
36:31into in a moment. Add more and more.
36:34Now we are doing what's called
36:36neoadjuvant therapy,
36:37and that's treatment which is
36:39actually given before surgery.
36:40So even before you have your
36:42breast tumor removed,
36:43treatments that go all through the
36:45body that both shrink the cancer,
36:47and more importantly.
36:49Eliminate if there were any any
36:52microscopic deposits of cancer in the body.
36:55And while we're not specifically
36:56going to talk about it
36:58in my presentation, be delighted to talk
37:01about some exciting innovations in anti
37:03estrogen therapy given before surgery
37:05or immune therapy given before surgery.
37:11I'll just version of the really
37:14cool before and after reconstruction
37:16picture or the radiation count.
37:19Quite live up to this the same level,
37:22but this is a cartoon of the cell cycle so
37:25when a cell divides including a cancer cell,
37:28it does so in an orderly process and you can
37:32think of it kind of like a circular assembly.
37:36Sembly line there are assembly line workers.
37:40Who sit at certain checkpoints and they can
37:43halt the assembly line if there is a problem.
37:46Now when you look at this,
37:49cut out the yellow box.
37:51This is a small window into a phase of
37:54the cell cycle where a cell is just
37:57getting ready to replicate all its DNA,
38:00and there's a lot going on
38:02in the cell at that time.
38:04So sort of in the middle you
38:07see that estrogen diffuses into
38:09cells and binds to its.
38:11Estrogen receptor,
38:12called the ER an that complex
38:14can go across the dotted line,
38:17which is the border of the nucleus.
38:20Bind to DNA and cause changes in genes that
38:24move the cell along towards replication.
38:28And so for a long time we've been
38:31using anti estrogen treatments to
38:33block this critical pathway in the
38:36cells going through their cell cycle.
38:39But there's a parallel pathway that
38:41involves these cycling and kinases,
38:44particularly CD K46,
38:45which is also critical in moving
38:48a cell into through this G1 phase
38:51of the cell cycle to where it's
38:54getting ready to replicate DNA
38:56and in exactly analogous manner 2.
38:59For a really bad bacterial infection,
39:01we may use two antibiotics
39:03to treat the same infection,
39:06or for HIV were using multiple
39:08antiviral drugs to halt the replication
39:11of HIV cancers no different than
39:13the concept that if you attack two
39:16growth pathways at the same time,
39:18you may have better results,
39:21has been a successful strategy in
39:23treating breast cancer so we can inhibit
39:26this cyclin dependent kinase 46 and block.
39:29Two pathways important in the cell cycle
39:31and that has proven to be remarkably
39:34effective in metastatic breast cancer.
39:37Breast cancer that has come
39:39back and spread to other places,
39:41doubling the amount of time that.
39:46Successful treatment with anti
39:48estrogen therapy last and among
39:50the really good things we're doing
39:52when we are inhibiting this CD.
39:5546 pathway along with the estrogen pathway.
39:58As we're causing a process called.
40:00Cellular senescence, a senescence is
40:03just the definition of a term where
40:07cells have outlived their replicative.
40:11Cannot divide anymore and when cells
40:13reach that point they do a lot of things
40:16that are really good for treating cancer.
40:19They release substances that turn
40:21on the immune system and help the
40:23immune system react to cancers.
40:25They also cause remodeling of the
40:28vasculature around tumors and
40:30help your own body fight cancers.
40:32So more to the point.
40:35At this year's European Society
40:38of medical oncology meeting big
40:40do meeting for medical Oncologist,
40:42this monarchy trial was presented.
40:44Really big study involved about 5600
40:47women who had high risk breast cancer.
40:50These are women who had four or
40:53more involved armpit lymph nodes or
40:56they could have one to three lymph
40:59nodes and really big tumors.
41:01These are women who were really
41:04concerned about risk of recurrence.
41:06Despite optimal local therapy and
41:09they were assigned the Standard anti
41:12estrogen therapy at their oncologist
41:14discretion or standard therapy.
41:16Chemists,
41:17I clip in a CD for CK46 inhibitor and
41:22their results are shown here in the.
41:26Or just the one below is magnified and
41:29this roughly 3% difference in cancer
41:31coming back at a site outside the breast,
41:35so lungs liver bones elsewhere,
41:37the kind that we are not able to cure.
41:41While this might not seem like a lot to
41:44the average person looking at these curves,
41:47this is a big big deal.
41:50The medical Oncologist is a 25%
41:52relative improvement in cure rate
41:54that we're seeing in only two years.
41:57And we anticipate that this is only
42:00going to get better as more years go by.
42:03And it is true that.
42:06Because overall,
42:07the outcome with breast cancer is good.
42:09You still need to treat a lot of women
42:12with this medicine to save one life.
42:14About 60 people with this medicine
42:16and all right. That seems like a lot.
42:19But when you think about what are
42:21the side effects of this medicine,
42:23it was actually quite well tolerated.
42:25There was some diarrhea which a
42:27curd in about 80% of people.
42:29So if you have a problem
42:32with Constipation of MSI,
42:33clip is the medicine that you want to take.
42:36There was some fatigue in about
42:391/3 of people,
42:40but rarely was that very severe and similar.
42:43There's some GI upset,
42:44but overall,
42:45in terms of serious or life
42:47threatening side effects,
42:48they really were not so this
42:51is going to become a very,
42:53very valuable addition for the treatment of
42:56women with high risk of cancer recurrence.
42:58Overnight became what I would
43:01consider the standard of care.
43:03And what we're doing at Yale as we
43:05are still we're participating in
43:07another trial that's looking at,
43:09is the same strategy going to be
43:11effective in women with lower
43:13risk breast cancers?
43:14So we saw from the monarchy trial
43:16that you need to treat roughly
43:1860 women to save one life,
43:20and if we look at a lower risk population
43:23is probably going to be more than 60.
43:26How much more than 60? We're not sure.
43:28Will it even be a statistically
43:30significant difference?
43:31We're not sure, but it's a critically.
43:34Important question for us to answer and
43:36available at all of our care centers.
43:42So we're going to leave the world
43:44of agg event hormone therapy behind
43:46for a moment to think about.
43:49Alright, we made a decision what the
43:51what your anti estrogen should be.
43:53If you have extra independent breast cancer,
43:56how long do you need to take these
43:59pills and in terms of politically
44:01moving the goal posts as you will,
44:04this is something with the goalpost have
44:06moved over the last couple of years.
44:09For decades.
44:10The standard duration of
44:11anti estrogen treatment.
44:12Was five years and then done
44:15but round about 10 years.
44:17We developed a new class of anti estrogen
44:19medicines that work via different
44:21mechanism and as we integrated those
44:24into common treatment many women
44:26had already been on tamoxifen for
44:28three years or five years and so was
44:31natural that the clinical trial said OK,
44:34you can add this medicine and we're
44:36going to do it for five additional years.
44:40In addition to the first three
44:42years of tamoxifen ya at.
44:44And that led to the natural question.
44:47Well, what if you started with
44:49Arimidex Femara or aromasin?
44:51These Roman taste inhibitors
44:53and got five years.
44:54Would adding another five years be
44:57beneficial and somewhat surprisingly,
44:58in 2020 we still don't really
45:00know the answer to this.
45:03For sure, the is longer,
45:05better question,
45:05at least for tamoxifen alone.
45:07This seems to be the case that
45:10longer is better.
45:1110 years improves cure rate
45:14compared with five.
45:15But for women who are starting
45:17with aromatase inhibitors,
45:18we just don't know and we're still taking
45:20a kind of 1 size fits all approach.
45:23So this next slide,
45:24which no one is going to be able to decipher.
45:28Just gives you a sense of the confusion
45:31that medical oncologists are confronted by.
45:33These are 10 trials in the left column,
45:3610 different trials looking at the
45:38optimal duration of anti estrogen
45:40therapy and the red box are people
45:42who received tamoxifen for the first
45:45five years and then going over to
45:47the right or what they received
45:49from the next five was that Aromat
45:51ACE inhibitor was another five
45:53years of tamoxifen and all of these
45:56studies when you look at the two
45:58columns over on the right.
46:00One is disease free survival.
46:02That's just the statistic
46:03for did cancer come back,
46:05either in breast or distant site and
46:07the next column is the critical column.
46:10That's the overall survival.
46:11Was there a difference in overall
46:14survival if you got extra anti
46:16estrogen therapy or not and
46:17while no one is going to be,
46:19I don't expect to be able to
46:22decipher these individual trials.
46:23The general theme is when you look
46:25at that disease free survival column
46:27you see that all those numbers
46:29are consistently less than one.
46:32There all about .8 indicating there
46:34appeared to be about 20% less breast
46:37cancer recurrence or second breast
46:40cancers in women who get more anti
46:44estrogen therapy five more years.
46:46But when you look at the final column,
46:49all of those numbers hover just around one,
46:51meaning it's not clear if we're
46:53saving lives or potentially simply
46:55delaying recurrence a little bit.
46:57And the medical oncologist response
46:59to all this has been, well,
47:01we're still not entirely sure,
47:02so for women who either have high
47:05risk breast cancer or women who are
47:07doing really well with their anti
47:09estrogen therapy with no side effects
47:11will keep it going for 10 years.
47:14And wouldn't it be nice if we had some?
47:17Test which could help us in this decision.
47:21And that's where we get to
47:23this breast cancer index test.
47:25And I'm going to pinch out if I
47:28can to try and highlight this.
47:30The breast cancer index is a test that's
47:33a little bit like the Oncotype DX,
47:36and some who are listening in may have
47:39had it Oncotype DX tests performed.
47:41The breast cancer index looks at the
47:44gene expression of five genes inside the
47:47cancer cells of the individual person,
47:49so this is not looking at statistics from.
47:5210,000 women this is looking at your cancer.
47:55Individually,
47:55Anna relates this level of gene
47:58expression to either a low risk or high
48:00risk of cancer coming back in lungs.
48:02Liver bones over the next five years,
48:05five through 10.
48:06So again,
48:06this is a test which is done
48:09right at the five year.
48:10If you will be a night old clubhouse
48:13turn and it can give us a sense.
48:16OK, what do we expect in the next five years?
48:19Do we expect that your breast
48:21cancer succeeded without?
48:22High risk of distant recurrence.
48:24Those five years or a low risk and
48:26manufacturers of the test have somewhat
48:28arbitrarily decided that while 5% or higher,
48:30they're going to high risk lower than
48:325% going to risk one of the nice things
48:35about the report is you get to see it
48:37and you get to make up your own mind.
48:40What's high.
48:41Risk is low disk.
48:43But what's really
48:44extraordinary about the test?
48:46Is not only does it give us a
48:49prognostic assessment of what's
48:50the risk of cancer coming back,
48:52but it predicts will another five
48:54years of anti estrogen therapy help?
48:56And is the only test of its
48:59kind that can do that?
49:00So this is a typical report that
49:03you might get back that lists
49:05the prognostic part at the bottom
49:07that this would be a low risk
49:10woman with a 2.2% risk of distant
49:12recurrence in years five through 10,
49:14and then above that it gives the.
49:16Predicted result,
49:17would we predict that an additional five
49:20years would add a significant risk reduction?
49:24So this is a test which actually
49:25in a study at Yellowstone,
49:27shown to be very helpful not only
49:29to doctors but people living with
49:31cancer to help them make informed
49:34decisions about do I want to take
49:36another five years of treatment?
49:37But what's been missing is the bulk
49:40of the data had common women who had
49:43received five years of tamoxifen.
49:45And as we just discussed,
49:47aromat ace inhibitors like Arimidex
49:49Femara aromasin have been around
49:51now for about 15 years,
49:52so most women now who are post menopausal,
49:55are completing five years
49:56of Aromat ACE inhibitor,
49:57and we want to know is this test.
50:00Just as well in this population,
50:03and at this year's Asco meeting,
50:05our big medical oncology
50:07meeting in North America,
50:08the answer was a resounding yes.
50:10That the breast cancer index is just
50:13as good at predicting the benefit
50:15of extended anti estrogen therapy
50:18in women who are completing five
50:20years of Aromat ACE inhibitor.
50:22And what this table is showing
50:25that in a subset analysis and
50:28were really Big 5000 woman trial.
50:31Those who were had involved
50:33armpit lymph nodes or not.
50:35If you had a what's called a
50:38high benefit from anti estrogen
50:40therapy it looked like taking five
50:43more years of antacid therapy.
50:46Reduce your risk by 2/3 or at least 2/3,
50:50whereas if you had a.
50:52Ratio of these two predicted
50:54genes that were low.
50:56You really did not have significant
50:58benefit to five more years
51:00of anti estrogen therapy.
51:02So big validation for what I think is
51:04going to be an increasingly utilized
51:07tool to help women make this decision.
51:10At five years and another population
51:12we've also struggled with our well,
51:15what about women?
51:16Who are her two enriched breast
51:18cancer that comprises roughly a
51:20fifth of all breast cancers and?
51:23We've been really uncertain as
51:25to what's the relative role of
51:27anti estrogen therapy in that
51:29group of women and do they really
51:31need 10 years or five years?
51:33Again,
51:34this another separate studies
51:35seem to indicate that even in
51:37the estrogen receptor positive,
51:39her two positive women,
51:41the breast cancer index is
51:43a very useful tool.
51:45Now we have at present three
51:47decision tools that help us
51:49with the decision at five years
51:51with this breast cancer index.
51:53We just talked about,
51:55there's a statistical model called
51:57CTS 5 and then we can retool
52:00archetype for women who have had an
52:02archetype at their initial diagnosis.
52:04All three of those can help
52:07us estimate risk of recurrence
52:08in years five through 10,
52:11but really only the breast cancer
52:13index gives us this added predictive.
52:16Information of would take in five
52:18more years would be helpful,
52:19OK?
52:22While that is exciting,
52:24what is even more exciting is a clinical
52:29trial that we are about to start at Yale.
52:33That really brings this down to the
52:37ultimate micro individual level.
52:39There is developing technology to look
52:42for cancer related DNA in people's blood.
52:46And a company called Natera does
52:49this by getting a sample of man
52:52or woman's tumor breast cancer,
52:54and they look for unique DNA
52:57sequences inside that cancer.
52:58All of our DNA has freckles in it.
53:02Like we all have freckles on our skin and
53:05they can identify these unique freckles
53:07that make your tumor cells unique.
53:10And they build a individual profile for you.
53:14And then they can look in your blood.
53:17At various time points after treatment
53:20and look for these unique freckles
53:23and we know that if we find cancer
53:26related DNA in the blood of a
53:29person who had early breast cancer,
53:32unfortunately the chance is very high
53:34that they will develop full blown
53:37metastatic breast cancer in the future.
53:39What's not known is.
53:41Is this an opportunity for us to
53:44intervene and cure that microscopic
53:46breast cancer by switching a womans anti
53:49estrogen therapy even before we can see it?
53:52Sort of the same idea but much more specific.
53:55Whereas the breast cancer index we
53:58just talked about kind of gives us this
54:01macro level view of might five more
54:03years of anti estrogen therapy be helpful.
54:06This natera assay is going to give
54:09us up-to-date individual information
54:10that what you're doing right now
54:12may not be working.
54:14And this may be an opportunity to
54:17switch horses before we develop
54:19evidence of metastatic breast cancer.
54:21So this is the way the clinical trial
54:24is going to work. Women who have.
54:28Breast cancer confined to breast
54:30or armpit lymph nodes who are at
54:33significant risk for recurrence will
54:35have a piece of their tumor sent
54:38Inotera or they will develop these
54:40specific individual specific assay
54:42and then women will do their anti
54:45estrogen therapy and they will be
54:48screened every six months by blood
54:50and if at any point during that five
54:53years we identify tumor specific
54:55DNA in the blood they are assigned.
54:58One to one to either continue
55:01their current treatment or to do a
55:04different hormone treatment.
55:05In this case,
55:06it'll be a shot called full best
55:09render faslodex and a different
55:11CD K inhibitor palbociclib.
55:13So again, this will really novel concept,
55:16exciting trial and hopefully it will help
55:19us both be much more reassured about the
55:23majority of women who will fall in the tumor.
55:26Dean, a negative population,
55:28cured their cancer.
55:30And give us a early warning,
55:33an opportunity for those
55:34women who may have sub,
55:37clinical or undetectable cancer potential.
55:39Only by circulating tumor DNA.
55:43Alright,
55:44so the last topic we're going to talk about
55:47is exciting new drug called Sacituzumab,
55:51which is a drug which is already
55:53FDA approved to treat women with
55:56metastatic estrogen progesterone
55:57and her two receptor negative.
56:00What we call triple negative breast cancer.
56:03Facet ISM is a member of a
56:06relatively novel class of medicines.
56:09It's an antibody.
56:10Antibodies are proteins that
56:12our own body makes, which.
56:14Bind to unique elements typically have
56:17infections to target them for Eradication,
56:20but antibodies can be engineered
56:22to recognize specific proteins
56:24on the surface of cancer cells,
56:27and this sassy twosome AB has been
56:30engineered to recognize Trope two.
56:33Trope Two is a substance which is
56:36expressed at high density on the
56:38surface of many different cancer cells,
56:41including breast cancer cells and to this.
56:45Anti Trump two antibody is fused.
56:47All these green dots which
56:49are is the payload.
56:50These chemotherapy molecules and the
56:52secret sauce of this treatment is the
56:55antibody binds to the cancer cell.
56:57It's taken up by the cancer cell
56:59in the chemo is only released in
57:02the cancer cell so it's highly
57:04specific for your cancer and it's
57:07the chemo is only released inside
57:09the cells so it does not cause a lot
57:12of side effects and what has made.
57:15There's company that developed this
57:17technology very prominent and lots of money.
57:20Is this special linker and the Linker
57:22is only broken that links the chemo
57:25to the antibody inside the cell.
57:27So here's a cartoon or what happens.
57:30The antibody binds the surface of
57:32the cell in the stroke two molecule.
57:35It's brought inside the cell
57:37into what's called an endosome.
57:39The endosome turns into a body
57:41that releases a bunch of digestive
57:43enzymes which cleave the chemo
57:45from this special Linker.
57:47And then that chemo drug,
57:49which is called SN 38,
57:51binds to cancer cell DNA
57:54and kills the cancer cells.
57:57And this is the data looking
57:59at Sacituzumab in women with
58:01metastatic triple negative breast
58:03cancer estrogen progesterone and
58:05her two negative breast cancer.
58:07So these were women who had received
58:10a lot of chemotherapy already.
58:12So population women or in
58:14a really tough situation.
58:16And what you see on that top line,
58:19which is the green line.
58:21These are women treated with Sacituzumab
58:24and the bottom line are women.
58:27Dad who received the therapy that
58:29physicians choice was thought to be
58:31the best available alternative therapy.
58:33And so the time until cancer grew
58:36and people needed another treatment,
58:38you can see on the left lower curve
58:41is substantially increased when
58:42you're treated with sassy twos map
58:45and that also translated into a
58:47very meaningful prolongation in
58:49how long women were surviving and
58:51the side of a profile is actually
58:54really good with this medicine.
58:57And this was the what I think even
58:59more exciting information from
59:01this year's asthma meeting that
59:03this trope to target is not unique
59:06to triple negative breast cancer
59:08cells or to bladder cancer cells.
59:10In fact,
59:11it's present on estrogen receptor
59:13positive breast cancer cells.
59:14Just so happened that the drug
59:17manufacturer made a decision that it
59:19was more expeditious for them to get
59:21it approved in triple negative breast cancer.
59:24But they reported this year
59:26a study looking at roughly
59:2835 women with estrogen receptor
59:30positive breast cancer.
59:32Received lots of chemo.
59:34Also giving this drug sassy to some
59:37app and what you see on the bottom
59:39left is what's called a waterfall plot
59:43in each bar represents an individual
59:45woman and the height of the bar above
59:49or below the X axis is whether their
59:52cancer grew or shrunk compared to baseline.
59:55And so when you see a
59:57waterfall curve like this,
59:58where the vast majority of women are.
01:00:01Pointed down that means the vast majority
01:00:04of women's cancer actually shrunk.
01:00:06Now in the oncology world,
01:00:09we use a change from baseline,
01:00:11a shrinkage of 30% as a definition of.
01:00:17Partial response,
01:00:18whereas a growth that's generally
01:00:20over about 15 percent 10 to 15%.
01:00:23We call progression.
01:00:24So the really critical
01:00:26things about this study,
01:00:27from my perspective is that only one
01:00:31women had progression from the 1st at
01:00:33the time of the first data recording.
01:00:36The vast majority of women either had
01:00:39stable disease or their cancer shrunk,
01:00:42and so that's really really
01:00:44encouraging stuff Ann.
01:00:46Is Why?
01:00:47We are thrilled that we are participating
01:00:50site in this tropics two trial,
01:00:53and that's a clinical trial that's
01:00:55exactly mirroring the registration
01:00:57trial for triple negative breast cancer.
01:00:59Women who have received treatment for
01:01:02estrogen receptor positive breath.
01:01:04Really neat thing about this
01:01:06study is you don't have to have
01:01:08received a lot of chemo,
01:01:10so this is going to be healthier.
01:01:12Population of women and we expect that
01:01:15any treatment it's going to work better,
01:01:17healthier you are and it will be
01:01:19assigned the sassy to some app.
01:01:21Or again,
01:01:22the treatment of Physicians Choice with
01:01:24Medecins which we already use which
01:01:27are highly effective in that setting.
01:01:29And that probably was my last slide.
01:01:34So I will.
01:01:37Turn it back over to you mera.
01:01:40If I can figure out how to do that.
01:01:43Yeah, that was fantastic and.
01:01:48Between the sassy and the tropics we
01:01:50have a lot to discuss so got a lot of
01:01:53questions that came through with your talk.
01:01:56One of 'em is from Donna asked what
01:01:58tests are available to see if there is
01:02:00a recurrence during the five years of
01:02:03post mastectomy anti hormone treatment.
01:02:05I mean I guess the questions could be like
01:02:08you know are there blood tests or their
01:02:10scans or images that should be done through?
01:02:13Yeah yeah. So that is one of the
01:02:16most frequent questions that we get
01:02:18asked and I have to acknowledge the
01:02:21answer is still really disappointing
01:02:24because after rigorously looking at
01:02:26looking at the currently available
01:02:28serum blood test tumor markers or
01:02:31doing cat scans every six months or
01:02:33monitoring for circulating tumor cells,
01:02:35we really have not identified a tool that
01:02:39impacts outcomes in a meaningful way.
01:02:41So it's still really old fashion.
01:02:44It's how you feeling.
01:02:45What's important to recognize
01:02:47about that is no surveillance.
01:02:49Imaging or testing does not mean
01:02:51we're going to ignore what happens.
01:02:53We have extraordinarily low thresholds
01:02:55to do imaging or diagnostic testing,
01:02:57but it seems to fly in the face of
01:03:00everything here all along, right?
01:03:02But early diagnosis saves lives,
01:03:03and that is critically important
01:03:05for breast cancer in the breast,
01:03:07and we're still working on the tools for
01:03:10early diagnosis for recurrence elsewhere.
01:03:13That's great, and then we have
01:03:15another question from Tina,
01:03:16this time regarding the DNA
01:03:18in blood clinical trials.
01:03:19Are they being done in patients
01:03:21after 10 years of either tamoxifen,
01:03:23arimidex or other forms of anti estrogen?
01:03:27So I suspect, unfortunately,
01:03:29like the pace is slow.
01:03:31Alright, so it's one thing to
01:03:33be able to detect a population.
01:03:36Women who are likely to recur.
01:03:38It's yet another critical thing
01:03:40to be able to prove we can do
01:03:43something different to help impact
01:03:45the outcome of those women,
01:03:47so I suspect that this circulating
01:03:49tumor DNA in the natera assays probably
01:03:52will not be available for common
01:03:55consumption until we've determined that.
01:03:57We can actually change therapy
01:03:59and improve outcomes,
01:04:00so I think we're probably like
01:04:03a couple of years off until
01:04:05these really hit Primetime.
01:04:07They this similar technology is not
01:04:09just specific for breast cancer,
01:04:11so it is being used in colorectal cancer now.
01:04:15Similar types of trials are being done,
01:04:17but it's the pace will be slow until enough.
01:04:25Then we just get the answer.
01:04:26Spencer We gotta do.
01:04:28That was really great.
01:04:29We have another question from Lynn
01:04:31who asks are women with hormone
01:04:34receptor positive cancers ever going
01:04:36to be able to take anything after
01:04:38menopause to help with all the
01:04:40hormone replacements stuff like skin,
01:04:42her libido, mood, memory,
01:04:43family fat and then I know
01:04:45that's a question of problems
01:04:47to your practice a lot.
01:04:49Yeah, yeah.
01:04:49So critically important people working on it.
01:04:52We will be doing more research neus.
01:04:54So there are some things we can
01:04:56do like for vaginal dryness.
01:04:59We know that Topical Vaginal estrogen
01:05:00is safe when used at minimally
01:05:03effective dose libido has just
01:05:05been extraordinarily frustrating,
01:05:06so have things like waking.
01:05:08I think it's a matter of
01:05:10with your oncologist.
01:05:11You just need to decide OK?
01:05:13Where is my risk profile set might
01:05:16weight gain ultimately be a bigger
01:05:18detriment to my health then staying
01:05:20on my anti estrogen therapy for an
01:05:23additional five years and so these
01:05:25are the kinds of individualized
01:05:27decisions that we need to make but.
01:05:30But I totally understand endocrine
01:05:32therapy is a long tough slug and we are
01:05:36trying to find ways to make it better.
01:05:40So as we wait for more questions to come in,
01:05:43I have one for Doctor Mastriani,
01:05:45you know, like what if a woman is
01:05:48addressing one side with cancer with,
01:05:50for example, mastectomy and
01:05:51reconstruction, but she wants
01:05:52to preserve our opposite breast.
01:05:54What are some options for for
01:05:56them on the opposite side?
01:05:59The great question.
01:06:00A lot of people like to match the natural
01:06:03breast and I I always have a Frank
01:06:06conversation with patients about that.
01:06:08It's not impossible,
01:06:09but we just sort of have to identify
01:06:13what goals the patient had.
01:06:15And one clothing. So are we going
01:06:17to match the volume of the breast?
01:06:20Do you want to have matching nipples?
01:06:23Can we match that with a secondary procedure?
01:06:25The biggest challenges I find actually
01:06:28our average women who have had children.
01:06:30They just have that dissent of tissue.
01:06:33And that's tougher to to address.
01:06:35But we can certainly address that
01:06:37with a procedure like a lift or
01:06:39putting an implant in there to
01:06:41give them a similar appearance.
01:06:43So there are many,
01:06:45many options.
01:06:46But I always try to talk to my
01:06:48patients and find out what their
01:06:49goals are and we try to match what
01:06:51I can do with what their wants are.
01:06:55Excellent and I have a question for a Andrew,
01:06:58you know one of those things that patients
01:07:01will often complain about is fatigue.
01:07:04During radiation. Is that something
01:07:06that we actually really see, or is it?
01:07:09And if we do, are there any
01:07:12options or strategy with the.
01:07:15Fatigue is probably on the order of
01:07:18maybe I would say 50 to 75% of patients.
01:07:20It's using pretty mild fatigue and
01:07:22all the symptoms of radiation.
01:07:24Let's say you. Have a five week course.
01:07:27They don't really start the first week.
01:07:30Probably don't even start the second week.
01:07:32Radiation side effects are always delayed,
01:07:34so they probably start.
01:07:35Maybe the end of the second
01:07:37week starting the third week.
01:07:38I personally found that patients who exercise
01:07:41more actually don't have that much fatigue.
01:07:43There probably is correlated,
01:07:44but there's no real study looking at that.
01:07:46And after radiation phased,
01:07:48fortunate thing about fatigue is
01:07:50generally a short term side effects,
01:07:51so that usually goes away within
01:07:53about a month.
01:07:55Excellent, have a couple of questions
01:07:58coming in for doctor fishback.
01:08:00Very popular tonight.
01:08:01Alexa ask is tamoxifen 10 milligrams
01:08:04daily just as effective as tamoxifen.
01:08:0720 milligrams a day and.
01:08:10The one other question for you
01:08:12is do you along the lines of,
01:08:14I think Anti estrogen therapies.
01:08:16Do you have to have the PCI test to
01:08:19decide to stay on meds for 10 years if?
01:08:22If so, do you have the test at
01:08:24five years after diagnosis or
01:08:26five years when you started the?
01:08:28Yeah, yeah.
01:08:29So the first question about the dose of
01:08:31tamoxifen that's really interesting one.
01:08:33It gets to how to drug companies.
01:08:36Pick the right dose right?
01:08:37So for a pharmaceutical company
01:08:39they have no interest in finding
01:08:41a minimally effective dose.
01:08:42That takes a lot of people in a lot of time.
01:08:46They want to very quickly determine
01:08:48what's a maximally tolerated dose
01:08:50and move that to clinical trials and
01:08:52that way they are sure their drug.
01:08:54If it doesn't work,
01:08:55it's not working 'cause
01:08:56they picked the wrong dose.
01:08:58So tamoxifen in the 1970s,
01:08:59when it was evaluated,
01:09:01there was a lot of good data
01:09:03that just 5 milligrams a day.
01:09:05Tamoxifen achieved significant blood
01:09:06levels and didn't have a lot of
01:09:09the side effects that 20 molded,
01:09:10but twenty was the maximally tolerated dose.
01:09:13And from then on became the dose
01:09:15used in all clinical trials.
01:09:17So there's no question in my
01:09:19mind that for many women,
01:09:2110 would be effective,
01:09:22but we just don't have 10s of
01:09:24thousands of people.
01:09:26Data demonstrating that 10
01:09:27is equivalent to 20.
01:09:28So if we reach a situation where a woman
01:09:31needs to be an anti estrogen therapy
01:09:33to prevent breast cancer recurrence,
01:09:36a lifesaving treatment and 20 is intolerable,
01:09:38then I think 10 is a reasonable thing to try.
01:09:42In fact,
01:09:42there's some recent data.
01:09:44In women with a much lower risk
01:09:47breast cancer problem DCIS that 5
01:09:49milligrams a day has a benefit that
01:09:51looks very similar to 20 so I would
01:09:54not advocate cutting your pills
01:09:56in half but but if we reached the
01:09:58point of just I'm either stopped.
01:10:01This pill or I'm going to find a better way,
01:10:04I think the Tensor East Wash now.
01:10:06The second question about the DCI.
01:10:08So yes,
01:10:08this is a test,
01:10:10which is typically done at five years.
01:10:12It is an increasingly popular test.
01:10:14I would not say it is yet to test that
01:10:16every woman needs to do in my own practice.
01:10:20For women who have really high
01:10:21risk breast cancer,
01:10:22several involved aren't that
01:10:24lymph nodes involved.
01:10:24I still really encourage women
01:10:26to stick with it for 10 years,
01:10:28but for women who have lower risk
01:10:30breast cancer have kind of struggled.
01:10:32With five years of treatment and
01:10:34really would rather be off if
01:10:35there's any more evidence that
01:10:37we can constantly stop it,
01:10:38I think it's really helpful test.
01:10:41Excellent and this one.
01:10:42I probably a combination
01:10:44of both Neil and Andrew.
01:10:46You mentioned new medications.
01:10:48This is from Elizabeth,
01:10:49who initiates the exploration invention
01:10:51of these new treatments, drug therapies.
01:10:54Is it the drug companies or
01:10:56scientists at the University?
01:10:58And I think it's new treatments.
01:11:00New drugs. Thoughts on that?
01:11:06Yeah, so regarding radiation,
01:11:08a lot of the new treatment techniques
01:11:10is initiated by physicians.
01:11:12Every single clinical particular
01:11:14clinic and treatment center has,
01:11:16even though they follow the same guidelines,
01:11:19may have slight level variations
01:11:21in terms of the clinical practice.
01:11:23So for example,
01:11:24the trial data mention that we're adopting
01:11:27the five whole breast radiation treatment.
01:11:30That was a variation that the University
01:11:33of Florence and Italy particularly did,
01:11:35and they publish that in.
01:11:37We're adopting it here,
01:11:39so in terms of radiation,
01:11:41a lot of these new techniques is by
01:11:44physician and by hospital to kind of
01:11:47publish their results and try to share
01:11:50with the General Medical community.
01:11:52But
01:11:53I think for the for the medicine part,
01:11:56it really is a unique,
01:11:58exciting collaboration between
01:11:59physicians in academia and industry.
01:12:01The positions in academia often do a
01:12:03lot of the baseline basic science work
01:12:05for some of these novel compounds.
01:12:08That industry then develops
01:12:09and industry more and more,
01:12:11they are able to screen millions, 10s,
01:12:14millions of compounds and come up with
01:12:16a lot of interesting ideas on their own.
01:12:19And the collaborate with the
01:12:21academic medical centers to.
01:12:23I'll get those ideas to people who need it.
01:12:27Doctor Mastriani had to drop off.
01:12:29She has. She had a screaming toddler
01:12:32in the background, so there are
01:12:34any questions for reconstruction.
01:12:35I'm happy to pass those along to her.
01:12:38She's she's just a phenomenal
01:12:40addition to our program.
01:12:41And you know, I was privileged to
01:12:44see her as a trainee in a residence.
01:12:47And now she's telling me
01:12:49what to do so it's fantastic.
01:12:52Along the lines of additional questions,
01:12:54what are thoughts on you know Neil?
01:12:57You mentioned a little bit of this
01:13:00and Andrew as well on deescalation so
01:13:02often we're trying to do, you know,
01:13:05get better, newer drugs more longer,
01:13:08longer courses of treatment
01:13:09so we can keep you know.
01:13:12Of course, you know.
01:13:13Survival is our number one concern.
01:13:15Yet sometimes like for some of the
01:13:18less advanced diseases like DCIS you
01:13:21mentioned and certain types of cancers.
01:13:23We may be overtreating as opposed
01:13:26to thinking of less treatment.
01:13:29Right,
01:13:30that is absolutely correct.
01:13:31I'm over the past year is
01:13:33radiation terms of cure rates,
01:13:34control of local regional disease
01:13:36has been pretty effective,
01:13:37and we've been developing
01:13:38our new technology and many,
01:13:40many studies in trying to reduce
01:13:42the side effects and that kind
01:13:44of in the name of the game.
01:13:46Fortunately,
01:13:46breast cancers when those cancers
01:13:47that has a much higher cure,
01:13:49an control rate compared to other cancers.
01:13:51So we actually have this privilege
01:13:53of spending a lot of time and
01:13:55energy trying to increase side
01:13:57effects that we might not have.
01:13:59For example in.
01:14:00Patients with brain cancer or lung cancer.
01:14:03So different trials like I mentioned,
01:14:05you know the fabric trial
01:14:07changing the fractionation,
01:14:08maybe adding on breath hold technique.
01:14:10All these different techniques
01:14:12is really used to try to focus
01:14:15patients in the Gray area where,
01:14:17where maybe the treatment doesn't have
01:14:19to be that long or that extensive or
01:14:22cover regional nodes when you only
01:14:25have maybe one lymph nodes compared
01:14:27to patients with four lymph nodes.
01:14:29So patients along the Gray area
01:14:32spectrum are targets where we want
01:14:34to tease out exactly which treatment
01:14:36could benefit them the most without
01:14:39causing that were side effects.
01:14:41Yeah,
01:14:41so
01:14:42I have the medical equivalent meddock
01:14:44equivalent in what Andrew said is,
01:14:46I think, somewhat shamefully,
01:14:48I think that medical oncologist have
01:14:51been slow to get to the game of
01:14:53Deescalation and have pursued a more
01:14:55is better philosophy for for decades.
01:14:57And but we, although late to the game,
01:15:00we very much been catching up.
01:15:02So I think the best example of that is
01:15:05this Oncotype DX test where a test which
01:15:09has allowed us to give fully 50% less.
01:15:11Chemotherapy to women with early
01:15:14breast cancer and it now, thankfully,
01:15:16is pretty much top of mind in
01:15:18terms of medical oncologists.
01:15:20How can we give less chemo?
01:15:23How can we ameliorate the
01:15:25toxicities of anti estrogen therapy?
01:15:27Those types of things we have,
01:15:29Android or Merriweather?
01:15:30We've highlighted a really terrific
01:15:32study was coming up for women with
01:15:35non invasive breast cancer DCIS
01:15:37looking at avoiding surgery and
01:15:39radiation altogether and seeing that
01:15:41does everybody with DCIS need to be?
01:15:44Treated,
01:15:44treated so we're cranking along
01:15:46at those interesting questions.
01:15:47Any of these trials are great,
01:15:50and I'm hoping they put me out of business
01:15:53so I can just become a smile. O Moderador,
01:15:56which do awfully well.
01:16:00I actually don't see any
01:16:01other questions that I know.
01:16:03The hour is late and I really
01:16:05first of all appreciate so much.
01:16:08Neil, Andrew and Melissa for your time,
01:16:10the audience, and you know the
01:16:12patients that we have the privilege
01:16:14of taking care of for your time this
01:16:17evening just to listen in to Smilow
01:16:19Cancer Center and the phenomenal
01:16:21work that's being done here.
01:16:22And with that this is being recorded so
01:16:26you can go back if you had questions and.
01:16:30Exactly and we're always happy
01:16:31to answer questions at anytime.
01:16:33Thank you so much, guys.
01:16:38Take care everyone, take care.