Imaging, Radiation, and Reconstruction
June 21, 2021June 18, 2021 | Drs. Regina Hooley and Christin Knowlton
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- 00:00Soon my name is Mara,
- 00:02Gulshan here at Yale University,
- 00:05Yale Cancer Center,
- 00:06Smilow Cancer Hospital.
- 00:07Welcome you to the third
- 00:10breast CME lecture series.
- 00:13This today we're really fortunate to have
- 00:16three phenomenal speakers and panelists.
- 00:18We're going to start with
- 00:20Doctor Regina Hooley,
- 00:21who's professor of Radiology vice chair
- 00:24in the Department of Radiology in the
- 00:27interim as division Chief for breast imaging,
- 00:29and then we go to Doctor Kristen Knowlton,
- 00:33our medical director for Radiation
- 00:35Oncology at Yale at Hamden,
- 00:37and then last but certainly not least,
- 00:40Doctor Tomer Abraham,
- 00:41who is our director of breasts.
- 00:44Microsurgical reconstruction and
- 00:45breast reconstruction here at Yale.
- 00:47The format is that will have
- 00:49three consecutive speakers.
- 00:50I really encourage you to put as
- 00:53many questions as you want into the
- 00:55chat box or the question to answer.
- 00:58Box will try to answer them as
- 01:00much as possible in real time.
- 01:02Some will leave two to the
- 01:04end for discussion,
- 01:06and with that I really appreciate everyone
- 01:08taking the time to to log in and listen.
- 01:11This is going to be recorded
- 01:14so you can go back.
- 01:16If you want or share this with
- 01:18friends and colleagues around the
- 01:20country and around the world,
- 01:22so with no further ado,
- 01:24we'll turn it over to doctor Doctor Hooley.
- 01:29OK, thanks so much doctor Golshan.
- 01:32It's really great to be here,
- 01:35so I'm going to start by sharing my
- 01:38slides and let me just get this.
- 01:41Uhm? Why OK? So?
- 01:44I'm going to talk a little bit about
- 01:47breast cancer screening and, you know,
- 01:49one size no longer fits all these days.
- 01:52There's we're moving towards a
- 01:54more personalized screening,
- 01:55so I'm going to review screening
- 01:57it and show you where it's going
- 02:00over the next 20 minutes or so.
- 02:03My disclosures I am on the Medical
- 02:06Advisory Board for dense breast dot
- 02:08dash info and that's where I took
- 02:10some of my tables and figures from.
- 02:13That's a website that has a lot
- 02:15of information on screening.
- 02:17It's accurate and it's for
- 02:19patients as well as providers.
- 02:22So I'll start by reviewing the
- 02:24background breast cancer course.
- 02:26Worldwide is the most common cancer in women.
- 02:29It accounts for about 1/4
- 02:31of all female cancers.
- 02:33Is the leading cause of cancer
- 02:35related mortality worldwide?
- 02:36About 15% of all female
- 02:38cancer deaths in the US.
- 02:41Lung cancer is number one
- 02:43for cancer related mortality,
- 02:44and interestingly,
- 02:45the rates of breast cancer is rising
- 02:48worldwide at about 6.4% per year.
- 02:51Nobody really knows why,
- 02:53but that adds up.
- 02:56The World Health Organization reports
- 02:57that in 2018 there were 2,000,000 cases
- 03:00of breast cancer diagnosed worldwide,
- 03:03and by 2040 that'll rise to 3,000,000,
- 03:06so it is significant.
- 03:08In general,
- 03:09the incidence of breast cancer is
- 03:11more frequent in developed countries,
- 03:13as noted on the blue map on the left,
- 03:16and this is likely due to
- 03:18screening mammography.
- 03:19However,
- 03:19women diagnosed in developing countries,
- 03:21as noted on the map on
- 03:23the red map on the right,
- 03:26are more likely to be diagnosed
- 03:28at an advanced age and are more
- 03:30likely to die from the disease.
- 03:32And maybe this is because there
- 03:34is pretends not to be formalized.
- 03:37Breast cancer screening in
- 03:39these developing countries.
- 03:41When it comes to breast cancer
- 03:42screening and mammography,
- 03:43we've certainly come a long way.
- 03:46Breast cancers.
- 03:48Screening and mammography was first
- 03:51introduced, probably in the 1960s,
- 03:53and this is a paper from 1967
- 03:56showing the new technology.
- 03:58At the time there was film screen,
- 04:01mammography, and zero mammography as well.
- 04:04Pretty basic stuff that,
- 04:05compared to our standards today.
- 04:08But even those studies were
- 04:10able to show some cancers.
- 04:13Of these days,
- 04:14of course,
- 04:15Thomas synthesis or the 3D mammogram
- 04:18digital breast tomosynthesis is
- 04:20becoming the standard of care
- 04:22where we can see explicit detail
- 04:25of the breast tissue as well as.
- 04:27Small or or subtle cancers that
- 04:30are not well seen on the 2D
- 04:33traditional mammogram alone.
- 04:34Our group at Yale was lucky to be
- 04:37one of the first centers in the
- 04:41United States to get tomosynthesis.
- 04:43I think it was back in 2011 and
- 04:46a few years after that we became
- 04:49fully all of our mammograms were
- 04:52tomosynthesis and we were leaders in
- 04:55publishing led by Doctor Leon Philpotts.
- 04:58And so showing that tomosynthesis
- 05:00is beneficial
- 05:01for screening and diagnosis of breast
- 05:04cancer among all women and among all ages.
- 05:10Some screening mammography
- 05:12has been shown to save lives,
- 05:14multiple randomized control trials,
- 05:15and observation.
- 05:16ULL studies have shown that breast cancer
- 05:19mortality is increased by about 20 to 40%.
- 05:21Is the only test that has been shown a
- 05:24clear mortality reduction of breast cancer,
- 05:26and this is mostly due to downshifting
- 05:29up stage two and hired a stage one.
- 05:32There are fewer node negative.
- 05:34There are fewer negative invasive cancers,
- 05:36less tumor process, better tumor biology.
- 05:38And among screening detected cancers
- 05:4075% or stage zero DCIS or stage one
- 05:43and among clinically detected cancer is
- 05:45more than 50% are stage two or higher.
- 05:49And here are some examples
- 05:51of some mammograms in women.
- 05:52On the left hand side of the screen.
- 05:55This is a 67 year old woman who had
- 05:57never had a screening mammogram.
- 05:59She is a palpable 4 centimeter mass.
- 06:02It's pirates 5. We know it's a cancer.
- 06:04This was a triple negative,
- 06:06high grade cancer and we would think
- 06:08that she would have, you know,
- 06:10regular speeding. Agra fee.
- 06:11We would have caught this at an earlier
- 06:13earlier stage and smaller size.
- 06:15On the other hand,
- 06:16in this patient there's a tiny new
- 06:18group of calcifications there.
- 06:20Linear their branching.
- 06:21She's 15-6 years old.
- 06:22She has a screening mammogram every year,
- 06:25so they're caught earlier,
- 06:26and this was a very tiny 1.5 millimeter
- 06:29grade, two cancer, High Ki 67.
- 06:31So presumably this is a life
- 06:34saving mammogram in this woman.
- 06:36So despite the success of mammography,
- 06:38it is imperfect,
- 06:39is particularly limited in
- 06:40women with dense breasts.
- 06:42The overall false negative rate
- 06:44of mammography among all breast
- 06:45densities is about 10 to 15% in
- 06:47the overall sensitivity is 70 to
- 06:4990% dense breasts make it hard for
- 06:51us because of the masking effect
- 06:53where cancers tend to be white spot.
- 06:56So there can be difficult to see
- 06:58with the white fiber glandular
- 06:59tissue versus women with non dense
- 07:02breasts where there's more fat and
- 07:04less white gland or tissue.
- 07:06And cancers are easier to identify.
- 07:09So screening mammography is very
- 07:11controversial, controversial.
- 07:11I think we all know that our
- 07:15patients know that it's hard to
- 07:17miss the articles in the.
- 07:19And in the press.
- 07:21Over the past decade or so,
- 07:24and screening has become more complicated,
- 07:27and this step partially because of the
- 07:30United States Protective Services Task Force,
- 07:33who first issued recommendations
- 07:35on screening mammography in 2009
- 07:37and then reinstated them again,
- 07:39didn't change them.
- 07:40Basically,
- 07:41in 2015 and basically gave screening
- 07:43mammography, AB, and even a C rating.
- 07:47They basically said that having
- 07:49a annual screening mammogram and
- 07:52women in there.
- 07:5340S was a C grade,
- 07:55meaning that this service might be.
- 08:00Offered in selected patients.
- 08:02Depending on some circumstances
- 08:04and then gave screening mammography
- 08:06every two years from age 50 to 74
- 08:10AB grade and you know when we're in medicine,
- 08:13we generally like A's that we should
- 08:16be offering this.
- 08:17But you know Decencies and also the
- 08:21changing recommendations didn't
- 08:22really sit right over all the task
- 08:25force again.
- 08:25Recommended against screening
- 08:27mammogram of women in their 40s.
- 08:29They also recommended against teaching
- 08:32self breast examination they were against.
- 08:35Clinical breast examination.
- 08:36There were against screening women over
- 08:39the age of 75 and they were really
- 08:43only for screening women every other
- 08:45year in the starting age 50 to 74.
- 08:48This is very controversial.
- 08:50Patient advocacy groups primary care,
- 08:52oncology, radiology. Perhaps?
- 08:53It was really just about saving money,
- 08:56because it's certainly the less we screen,
- 08:59the more money we're going to
- 09:02save on healthcare dollars.
- 09:03And in all fairness.
- 09:05These recommendations are very similar to
- 09:07other countries that have nationalized
- 09:08health services and health programs,
- 09:10but we don't have that
- 09:12here in the United States.
- 09:13So saying that this is what we
- 09:15should do in in a country that
- 09:18doesn't have a full National Health
- 09:20Service doesn't seem to be fair,
- 09:22and not mentioning that at
- 09:24all doesn't seem fair.
- 09:26I do want to focus on the fact that we really
- 09:29should be screening women in their 40s,
- 09:31and if there's one thing that you
- 09:33should take away for anyone who doesn't
- 09:36believe in screening women in their 40s,
- 09:38we need to screen women in
- 09:40their 40s every year.
- 09:41So, so please take, you know,
- 09:43lock this in from this,
- 09:44talk women in their 40s have
- 09:46higher interval cancer rates.
- 09:48They have denser breasts.
- 09:49We know that interval cancers that are
- 09:51diagnosed between having a normal mammogram.
- 09:53These are usually symptomatic.
- 09:54Cancers tend to be more aggressive.
- 09:57Cancers in women have a shorter sojourn time,
- 09:59and they tend to be faster growing.
- 10:02We also know that.
- 10:05There's higher survival for earlier
- 10:07stage tumors, and, importantly,
- 10:08there's ethnic differences.
- 10:10Black and Hispanic women have a peak
- 10:13incidence of breast cancer in ages 46 to 47,
- 10:16so telling having a sweeping
- 10:18statement that says,
- 10:19you know we should only start
- 10:22screening at age 50 is really doing
- 10:25these patients a major disservice.
- 10:28Uhm?
- 10:30Here this graph shows that you
- 10:32know breast cancer in the 40s,
- 10:35accounts for about 20% of
- 10:37all invasive breast cancer,
- 10:38so it is a considerable fraction
- 10:41of the disease burden.
- 10:42So it is very important.
- 10:45So the screening guidelines,
- 10:47as they stand now.
- 10:49Among various organizations,
- 10:50looks kind of confusing in this table,
- 10:53but it's pretty.
- 10:56Think it's really pretty straightforward.
- 10:58Basically, most organizations
- 10:59say you should start at age 40,
- 11:02and with the exception of the
- 11:04task force were offer it.
- 11:06So again,
- 11:07this this reflects the patient
- 11:09shared decision making with ACOG
- 11:11and the American Cancer Society
- 11:13has the option also discharge date
- 11:15page 40 and says really start
- 11:18annual screening at age 45,
- 11:19so the American Cancer Society sort of
- 11:22bridge the gap between societies like
- 11:25the American College of Radiology.
- 11:27And the United States Protective
- 11:29Services Task force.
- 11:30Life expectancy is a little bit
- 11:32all over the place.
- 11:33I'm not so sure something
- 11:35magical happens at age 75.
- 11:36I think it's better to limit
- 11:39screening when life expectancy
- 11:40is less than 10 years,
- 11:42because we know these patients
- 11:43are not going to really benefit
- 11:45as much from early detection.
- 11:47So we have healthy patients who
- 11:49might be 76 years old and they
- 11:51should still have a mammogram,
- 11:53perhaps, maybe not annually.
- 11:55Perhaps we can even consider
- 11:57every one to two years.
- 11:59And then we have patients who might
- 12:01be 70 or 69 years old or whatever,
- 12:03or not that healthy.
- 12:04And maybe don't need to
- 12:06have a mammogram as well.
- 12:08And again, as far as the interval goes,
- 12:11most people say annually,
- 12:12maybe every one to two years the
- 12:16the task force being the extreme
- 12:18of every every other year.
- 12:20So in addition to the variable
- 12:23mammographic screening recommendations,
- 12:24supplemental screening is also an
- 12:26option for many of our patients.
- 12:28This includes ultrasounds and MRI.
- 12:30There's also newer technologies
- 12:32such as molecular breast imaging
- 12:33and contrast enhanced memo that are
- 12:36really investigational at this time,
- 12:38but they are on the verge of being
- 12:41offered outside of the screening trials.
- 12:43There are limited screening
- 12:45trials that are going on.
- 12:47So these tools are right around the corner.
- 12:50I believe for more widespread use,
- 12:52widespread clinical use,
- 12:53but I'm only going to review
- 12:56screening ultrasound and MRI today
- 12:58because of the time constraints.
- 13:00So breast ultrasound screening is linked
- 13:02to death dense breast notification laws.
- 13:04We do a lot of breast ultrasound
- 13:06screening in Connecticut because
- 13:07we were the first state to have
- 13:09a breast density notification
- 13:10law which was passed in 2009.
- 13:12Coincidentally the same month
- 13:14that the United States Protective
- 13:16Services Task Force told us that
- 13:17we should stop screening women in
- 13:19their 40s and then we have the
- 13:21Connecticut State saying that we
- 13:23should be offering patients with
- 13:25dense breast screening ultrasound.
- 13:27The restless notification.
- 13:28Just as an aside,
- 13:30has become quite popular,
- 13:31I think over 30 states in the United
- 13:34States have breast density notification laws.
- 13:37There are countries in Europe and South
- 13:39America that are considering breast.
- 13:44Density notification guidelines as well.
- 13:48And women with dense breasts do benefit
- 13:51from having a screening ultrasound.
- 13:53Overall, the cancer detection rate is about
- 13:55two to four per thousand women screen.
- 13:58This is in addition to the approximate
- 14:005 cancers per thousand women
- 14:02screen detected on mammography.
- 14:04We know that most cancers detected on
- 14:07screening ultrasound are small and node
- 14:09negative and tend to be early stage,
- 14:11so it's rational to think that
- 14:14finding these mammographic Leopold
- 14:16cancers at an early stage in smaller
- 14:18size will improve overall mortality.
- 14:21Ultrasound screening is really
- 14:22well accepted by our patients.
- 14:24It's relatively inexpensive.
- 14:25It costs about the same price as a mammogram.
- 14:28There's no Ivy contrast.
- 14:30There's no compression.
- 14:31It's widely available, so it can work.
- 14:35Which is why we offer it to our patients.
- 14:39It also performs very well in
- 14:41women with dense breast tissue
- 14:43before the mammogram is limited,
- 14:45and that's because of the
- 14:47contrast on ultrasound.
- 14:48These small cancers on ultrasound
- 14:49tend to be dark or hypoechoic,
- 14:52and dense breast tissue tends to look
- 14:54echogenic or white on the ultrasound,
- 14:57so we can see these little cancers that
- 14:59are draped in the glandular tissue fairly
- 15:02well and they will be mammographic.
- 15:04Leah called because they're just hiding
- 15:08behind this glandular tissue as well.
- 15:11Breast density is also important,
- 15:12so I just want to review this briefly
- 15:15because most of our more personalized
- 15:17community in the direction that we're
- 15:20going to go to is going to include
- 15:22breast density as a factor in what
- 15:24kind of screening patients should get
- 15:26breast dense breasts is very common.
- 15:29It's seen in about 50% of all
- 15:31women in the United States.
- 15:33We know there's an increased
- 15:34risk of breast cancer in women.
- 15:37It's a 2/6 times increased risk,
- 15:39and it can be confusing.
- 15:41When you see what they did,
- 15:43you know two times increased risk and
- 15:45then we'll see another article that
- 15:47says four to six times increase risk,
- 15:49and that's because it really depends
- 15:51on what breast density category
- 15:53you're comparing.
- 15:54So if you compare women with extremely
- 15:56dense breasts with women with fatty tissue.
- 15:59Then the increased risk of developing
- 16:01breast cancer for women with extremely
- 16:03dense breasts is 4 to 6 times higher
- 16:06than the women with fatty breasts.
- 16:08However,
- 16:09that's the minority of our patients
- 16:11in the United States.
- 16:12Only about 10% of women have extremely
- 16:15dense breast tissue and only about
- 16:1710% of women have fatty tissue.
- 16:19So 80% of our patients have
- 16:21heterogeneously dense breasts or
- 16:23scattered fibroglandular tissue.
- 16:25And so if you compare women with
- 16:27heterogeneously dense breasts with fatty
- 16:29with with scattered fibroglandular,
- 16:31then you have only about two
- 16:33times increase risk.
- 16:34So that's why that risk is variable,
- 16:36so it does.
- 16:37It is considered however,
- 16:39a intermediate risk factor for breast cancer.
- 16:41It limits the mammogram.
- 16:43There are higher interval cancer
- 16:44rates and worse prognosis for
- 16:46these clinically detected cancers.
- 16:48So that's why breast density
- 16:49is important and it can only
- 16:51be diagnosed on a mammogram.
- 16:53It can be diagnosed based on.
- 16:56A breast exam and if the patient's breast
- 16:58exam is sort of lumpy and difficult to do.
- 17:01Another option for women with dense
- 17:03breasts is fast MRI screening.
- 17:05It has been proposed for average risk.
- 17:07Women with dense breasts.
- 17:09It is been being done clinically
- 17:11in other parts of the country.
- 17:13There's very little of it done
- 17:15in Connecticut, but for example,
- 17:17University of Pennsylvania does a
- 17:19lot of fast, summarized meeting
- 17:20for women with dense breasts.
- 17:22The first study was published
- 17:24back in 2014 by Christiana Cool.
- 17:26She's a highly regarded a radiologist
- 17:28in Germany an she showed that with a.
- 17:31Very fast acquisition time of three minutes,
- 17:33as opposed to about the the acquisition
- 17:36time or scanning time of a traditional MRI,
- 17:38which is about 10 or 15 minutes.
- 17:42We could detect cancers at a very
- 17:45high rate of 18 per thousand,
- 17:47and this has been replicated
- 17:49by other studies as well.
- 17:51So overall, the cancer detection rate
- 17:53of MRI's about 15 to 18 per thousand,
- 17:56which is higher than screening ultrasound.
- 17:58That supplemental yield is only
- 18:00about two to four per thousand.
- 18:02But MRI is more expensive and
- 18:05requires Ivy contrast.
- 18:06There's not a lot of MRI scanners
- 18:08out there as opposed to ultrasound,
- 18:11so it's not as.
- 18:12Easy to perform.
- 18:13Patients may not like it as well.
- 18:16Takes longer,
- 18:16but it does work.
- 18:18The two year validation showed there
- 18:20were no interval cancers so it was
- 18:22really catching all those cancers.
- 18:24The sense the negative predicted
- 18:26value was high and the specificity
- 18:28and positive positive predictive
- 18:30value are also very good as well.
- 18:32So here is a 61 year old patient
- 18:34with a pathogenic BRACA mutation
- 18:36and Paris producting something over
- 18:38ectomy with a negative mammogram,
- 18:41and she had a MRI six months later
- 18:43and they saw this little cancer and
- 18:46detected this so it can work in women
- 18:49with dense breasts and this woman.
- 18:52She also had high risk and which is
- 18:54where we do most of our breast MRI in
- 18:57our practices for high risk screening,
- 19:00and that's traditional.
- 19:02I was screening MRI for high risk patients.
- 19:05Here's the list there Braca positive
- 19:08patients they they have some of these
- 19:10syndromes may have chest radiation,
- 19:12usually eight years earlier,
- 19:14part age 30,
- 19:15an overall lifetime risk of
- 19:17greater than 20% high risk women.
- 19:19We recommend that they have an annual
- 19:22mammogram and MRI beginning around age
- 19:2425 to 30 and again this is the BRACA
- 19:27positive patients and another high
- 19:29risk patients and this is recommended
- 19:32by the American College of Radiology
- 19:34and the American Cancer Society.
- 19:36We also know that it's reasonable
- 19:38to delay the onset of mammographic
- 19:40screening until the age of 30.
- 19:42In some of these patients,
- 19:44and that's because of the radiation risk.
- 19:46These patients are known to have
- 19:48increased radiation sensitivity,
- 19:49particularly the BRACA one carriers
- 19:50and the P53 carriers, as well.
- 19:55So breast cancer risk
- 19:56evaluation is a growing program.
- 19:59Most more and more breast centers today are
- 20:02offering breast cancer risk assessment.
- 20:05This is in lieu in in coordination
- 20:07with interest in population health.
- 20:10We're doing more screening not
- 20:12only for breast cancer, but colon,
- 20:15cancer, and other cancers as well.
- 20:18So with breast cancer risk evaluation,
- 20:21there are multiple risk assessment
- 20:24tools that are very available online
- 20:26and the estimated risk can really
- 20:29vary depending on which model you use.
- 20:32Most centers are going for the tire
- 20:35acoustic model that's most widely
- 20:37used and that also incorporates
- 20:39breast density into that model.
- 20:42When we think about breast cancer risk,
- 20:45we have to know that risk changes overtime.
- 20:49Unknown risk and change every year.
- 20:51For example,
- 20:51you can have a patient who is just an
- 20:55average risk and then her sister was
- 20:57diagnosed with breast cancer at age 39,
- 21:00and that's going to bump up her her
- 21:02risk for breast cancer the following
- 21:04year and overtime the lifetime risk
- 21:07increases decreases, excuse me,
- 21:09but the five and 10 year breast cancer
- 21:12risk is also proportional to age,
- 21:14so it's complicated and that's
- 21:16something that I think most breast.
- 21:19Centers,
- 21:19including our own will be doing
- 21:21within the next 5 to 10 years,
- 21:23so we're really moving beyond just starting
- 21:26at age 40 and having a mammogram every year,
- 21:29which is nice and simple,
- 21:30and it's nice for you know,
- 21:32buzzwords and things like that,
- 21:34and advertising to something like this,
- 21:36which looks really complicated,
- 21:37but it's really not that complicated,
- 21:39so let me just review with you.
- 21:42Review this with you.
- 21:43So the first question is,
- 21:45does the patient have at least
- 21:47a 10 year life expectancy?
- 21:49If not,
- 21:50then she would only have breast imaging is
- 21:52there's a clinically suspicious finding.
- 21:54The majority of our patients will have a
- 21:5610 year life expectancy and then we ask,
- 21:59is she under the age of 25?
- 22:01A 75?
- 22:01If not,
- 22:02she's over age 75 with healthy then
- 22:04maybe she would have an annual
- 22:06or BI annual mammogram.
- 22:07Most of our patients are going to
- 22:10be under the age of 75 and then
- 22:12we're going to look at the wrist and
- 22:14if she is at high risk for breast
- 22:17cancer then we would recommend
- 22:18annual contrast enhanced.
- 22:19MRI beginning at age 25 or 30 and
- 22:22mammography beginning at age 30,
- 22:24she can't have an MRI because it's she
- 22:26can tolerate it or for whatever reason.
- 22:29Then she would have an annual screening
- 22:31ultrasound in addition to her mammogram.
- 22:33The majority of our patients that
- 22:35we are not going to be increased
- 22:38risk and so then we want to be sure.
- 22:41That they are under the age of
- 22:43over the age of 40.
- 22:45If they're not over the age of four.
- 22:47If they're not over the age of 40,
- 22:50and we would just tell them to
- 22:52start really screening at 40 at 40,
- 22:54we do the baseline mammogram.
- 22:56Of course,
- 22:56we always want to synthesis if
- 22:58it's available,
- 22:59and if she has dense breast tissue,
- 23:01then we would also offer them
- 23:03screening ultrasound or at some
- 23:05places screening MRI as well.
- 23:06So that's the algorithm
- 23:08where it stands today.
- 23:10What about the future?
- 23:12There are going to be more screening options.
- 23:15We're going to have advancing knowledge
- 23:17of genetics so it will be better risk
- 23:19assessment and more personalized
- 23:20medicine will have new technology.
- 23:22As I mentioned, molecular breast imaging,
- 23:24contrast enhanced mammography,
- 23:25and of course AI will be more patient,
- 23:27shared decision making.
- 23:28We're going to be talking more patience
- 23:30and helping them filter information,
- 23:32medical information and guide
- 23:33their decisions.
- 23:34And of course, health.
- 23:36Health care economics is going to play a
- 23:39part in how we screen our patients as well.
- 23:42And what makes the most sense?
- 23:46Briefly, I'm just going to
- 23:47touch on overdiagnosis.
- 23:48I know that there's some people probably
- 23:50listening and thinking we shouldn't
- 23:52screen so much because of overdiagnosis.
- 23:54We could talk entire day about overdiagnosis,
- 23:56but I've condensed it into two slides,
- 23:58and here's an example of a case
- 24:01of over diagnosis of 59 year old.
- 24:03She had a mass president or left
- 24:05outer breast stable for five years.
- 24:07It looks just like a little lymph node.
- 24:09We do tomosynthesis the first
- 24:11time she has atomo exam,
- 24:12and there's little speculations.
- 24:14And this turns out to be a great two tubular.
- 24:17My cancer probably would have done anything.
- 24:20It's a low grade cancer and so perhaps
- 24:22this is a true case of overdiagnosis.
- 24:26We know that some screening detected cancers
- 24:28may never become clinically evident.
- 24:30They Sgro very slowly with patients
- 24:33that die of something else before
- 24:35cancer becomes symptomatic.
- 24:37This example would be low grade
- 24:39DCIS in an elderly patient.
- 24:41We might over treat these patients and give
- 24:44him and subject them to potential hard.
- 24:47But the key is we don't know yet
- 24:49which low grade cancers will become
- 24:51lethal and when they'll become lethal,
- 24:53and so hopefully more research
- 24:55will be able to.
- 24:57To identify these cancers so that we'll know
- 24:59more where we need to really treat them.
- 25:01Where we can stand back a little bit.
- 25:05AI tools and population health and
- 25:07new technology are going to allow
- 25:09us to screen smarter.
- 25:11We're going to know who needs
- 25:13more and who needs less screening,
- 25:15but it's going to take a lot of outcome
- 25:18analysis and sufficient data right now.
- 25:21Our data collection is not that great.
- 25:23Most of the cancer registries that.
- 25:28Collect information on cancer.
- 25:29Breast cancer. Do not look at the
- 25:31method of detection so we don't know
- 25:33how these cancers are being diagnosed,
- 25:36whether they are palpable
- 25:37or whether they had to mow,
- 25:39or that whether they were diagnosis
- 25:41on screening ultrasound or MRI.
- 25:42So the American College of Radiology is
- 25:45working to include method of detection
- 25:47in the BI RADS and then when we do that,
- 25:50hopefully the cancer registries
- 25:51and the national databases will
- 25:53accept this so that we can collect
- 25:56information on new technology and
- 25:58figure out what works and what doesn't.
- 26:00So in summary,
- 26:01annual screening mammogram beginning
- 26:02at age 40 saves the most lives
- 26:04women with dense breasts have
- 26:06the option to choose supplemental
- 26:08screening ultrasound or MRI,
- 26:09high risk women benefit from annual MRI
- 26:11in addition to screening mammography.
- 26:13Often this will start before
- 26:15the age of 40 and just one key.
- 26:17If a patient is having a supplement,
- 26:20an MRI in addition to our mammogram,
- 26:22she really doesn't need a
- 26:24screening ultrasound as well.
- 26:25We know in the future,
- 26:27vascular based imaging
- 26:28will become more common.
- 26:30It's interesting vascular based
- 26:31imaging may not necessarily require
- 26:33Ivy contrast routine breast cancer
- 26:35risk assessment will probably be
- 26:37available to all women and artificial
- 26:40intelligence will definitely enhance
- 26:41the delivery of breast cancer
- 26:43screening at multiple levels.
- 26:45From effective efficient scheduling
- 26:47to managing and analyzing new data to
- 26:50helping the radiologist read better
- 26:51and faster and more accurately,
- 26:53and also again help us determine
- 26:56who needs what when so that we can
- 26:59really serve our patients very well.
- 27:02So I want to thank you for your
- 27:04time and attention and will be
- 27:06available for questions later.
- 27:08Thanks, thank you Doctor Holy,
- 27:10that
- 27:10was fantastic. I mean honestly,
- 27:12the the amount of work that the
- 27:14our breast imaging colleagues
- 27:15and yuan in our group and others
- 27:18have done is is truly remarkable.
- 27:20And there's just so much new excitement
- 27:23in the pipeline and kind of figuring out
- 27:26what the next steps are going to be great.
- 27:29Next, move on to Doctor Knowlton to
- 27:32discuss some of the recent changes and
- 27:36advances in radiation therapy and.
- 27:39The floor is all yours.
- 27:46Hope you're on mute still.
- 28:18So while we're waiting
- 28:20for the slides to pop up.
- 28:24Regina, what are your thoughts
- 28:25on how to screen an elderly
- 28:27woman after an index cancer?
- 28:29For example, an 85 year old with a newly
- 28:32diagnosed breast cancer after treatment,
- 28:34does she need follow up image in?
- 28:37This is from Doctor Berger. Really
- 28:39great question.
- 28:40Yeah so generally women you know around
- 28:4285 or 86 their their life expectancy.
- 28:44Even healthy women is probably around
- 28:46six or seven years where the benefit of
- 28:49early detection probably is not useful.
- 28:52That said, I think it really depends on.
- 28:54On how healthy the patient is,
- 28:56maybe she still likes having a mammogram
- 28:59love these older ladies of her healthy.
- 29:01They still want to come in and get
- 29:03their mammogram maybe every other year.
- 29:06I just wouldn't push it,
- 29:07but there is still some shared decision
- 29:09making there got it excellent.
- 29:14Hopefully you see my slides properly now.
- 29:17Looks great. OK, great, thank you.
- 29:19So my title is as you can see is
- 29:22deescalation of radiation therapy
- 29:24for breast cancer for breast cancer.
- 29:27At less is more.
- 29:32OK so I have no conflict of interest to
- 29:35report related to this presentation an any.
- 29:38I do not unfortunately have as many awesome
- 29:40pictures as our two other presenters.
- 29:43However, any pictures that were used
- 29:45here were taken from sites that allow
- 29:48use of their photos in this setting.
- 29:51So when I after the title was submitted,
- 29:54you know D escalation in the setting of,
- 29:57you know, radiation therapy in
- 29:59the setting of breast cancer.
- 30:01I actually looked up the word
- 30:03deescalation and I think maybe my title
- 30:05is not grammatically correct because
- 30:08Merriam Webster Dictionary does not
- 30:09say that this is a noun in anyway
- 30:12and I tried hard copy and online.
- 30:14It is a will say that it is a verb that
- 30:18can mean to limit to decrease in extent.
- 30:22Are to decrease in volume or scope.
- 30:24I was able to find a definition for
- 30:26the noun in the free dictionary,
- 30:29which is a reduction in intensity.
- 30:31So if we have any people that are
- 30:33very much on top of their grammar
- 30:35and my title may not be correct,
- 30:38I will say however that the title is more
- 30:41in the spirit of the Marian Webster.
- 30:44Definition where we are in the modern era,
- 30:48aiming to limit the radiation limit,
- 30:51the number of fractions limit the
- 30:53dose that they treatment volumes and
- 30:56also omit radiation when necessary.
- 30:59Really the free dictionary definition
- 31:01doesn't make sense because we're
- 31:04not really reducing the intensity
- 31:06of the radiation.
- 31:07What we do when we are changing the
- 31:11fractionation to a shorter fractionation
- 31:13is we are using newer schemes of radiation.
- 31:17To deliver the same biological
- 31:19effective dose so I do not feel that
- 31:22the free dictionary definition really
- 31:24beats what's happening in radiation.
- 31:26But the Marian Webster one does.
- 31:29So here we see, this is how we are D.
- 31:33Escalating as I had mentioned with
- 31:34the decrease in number of fractions
- 31:36decrease in volume of tissue treated
- 31:38an omission of radiation therapy
- 31:41for appropriate candidates.
- 31:42And this really does fit the less
- 31:44is more if we have less radiation
- 31:47we will have increased compliance.
- 31:49People will have if the fractionation
- 31:51scheme is more convenient for them,
- 31:53whether they have traveled issues
- 31:55or working issues.
- 31:56We're going to have more patients
- 31:58that will be able to get it with less.
- 32:01Stress there will be increased
- 32:03acceptance of the treatment course
- 32:05increased time for patients to work
- 32:08or to pursue their hobbies or take
- 32:10care of their families and increase
- 32:13quality of life.
- 32:16So moderate fractionation
- 32:17is now really old news.
- 32:19At this point, we've all seen it.
- 32:22This is what it is now.
- 32:24Truly in the United States,
- 32:26the new standard of radiation therapy
- 32:28for the intact breast standard or
- 32:30conventional radiation to the whole breast.
- 32:33It was for several decades,
- 32:3550 Gray and 25 fractions,
- 32:37meaning that the patient
- 32:38needed to come for five weeks.
- 32:41And then there would be an optional
- 32:44tumor bed boost of an additional
- 32:4610 to 16 Gray and five to 8.
- 32:49Actions which many women have
- 32:51received over the years,
- 32:52so that's six to six and a
- 32:55half weeks of daily treatment.
- 32:57Moderate fractionation for whole
- 32:59breast irradiation therapy,
- 33:00which I'd like to stress in at this
- 33:03time is without including the nodes.
- 33:06This is the new standard where we
- 33:08where the whole breast is being
- 33:11treated in 40 grey and 15 fractions
- 33:14or 42.5 Gray and 16 fractions.
- 33:16That's really institutional preference.
- 33:18Our institution at Yale we use
- 33:21the 40 grey in the 15 fractions
- 33:24from the start B trial,
- 33:25and for these patients there's
- 33:27an optional tumor bed boost 10
- 33:30Gray and for fractions.
- 33:31So we're taking the standard or
- 33:34conventional fractionation of five
- 33:36to six to six and a half weeks,
- 33:38and now it's become three to
- 33:40four weeks for the patient.
- 33:44And of course there's some
- 33:46data to back all of this up.
- 33:49These are the three largest trials
- 33:51that have the longest follow-up that
- 33:53are used to backup or support the
- 33:56use of moderate hypofractionation.
- 33:58All three trials to start a the start B, and.
- 34:02There's no great name for this one.
- 34:05The Canadian Ontario Wayland trial.
- 34:07Depending on who you're talking about.
- 34:09I learned from this.
- 34:10I need to have make sure that any
- 34:13trials I have have a have a catchy name,
- 34:16but the start a trial and start be
- 34:18were done in England and the obviously
- 34:21the Canadian trial was done in Canada.
- 34:23They all compared their moderately
- 34:25hypofractionated regimens in whole
- 34:26breast radiation therapy to the standard
- 34:28conventional fractionation of welding.
- 34:29I guess we're going to call that conventional
- 34:32'cause modern hypo frack is now standard,
- 34:35but 50 Gray in 25 fractions was the
- 34:37standard arm and all Childs found
- 34:40no significant difference in local
- 34:42regional recurrence and overall
- 34:45survival for the patients.
- 34:47At 10 years they did all use a slightly
- 34:50different fractionation scheme to start.
- 34:53A trial,
- 34:54had had patients receiving 41.6 Gray or
- 34:5739 Gray and 13 fractions over 5 weeks,
- 35:01which is approximately 3 fractions per week.
- 35:04It's a little bit of.
- 35:06More challenging regimen to schedule,
- 35:08so most institutions are not
- 35:10really using this regiment,
- 35:11but it is interesting that they did.
- 35:14Note that a significant significant
- 35:16decrease in the number of patients
- 35:18with breast induration adima intellect
- 35:21until inject ages in the 39 Gray
- 35:23arm compared to the standard frac.
- 35:25The 41.6 Gray arm did not really
- 35:28do any better as far as then the 50
- 35:31Gray arm as far as acute effects
- 35:34an late term effects as that.
- 35:37Start B, which is what Yale is using.
- 35:40That's the 50 Gray and 15 fractions.
- 35:42So once a day Monday through Friday,
- 35:45that's three weeks.
- 35:46So once again their outcomes,
- 35:47local region of occurrence,
- 35:49overall survival at 10 years
- 35:51was the same with the 50 Gray,
- 35:53and there was a significant
- 35:55decrease in breast shrinkage,
- 35:56breast edema and telangiectasia.
- 35:58But age is in the 40 great arm.
- 36:01The Canadian trial was interesting.
- 36:03That is slightly different.
- 36:0442.5 in 16 fractions,
- 36:06so that's three weeks and a day.
- 36:10Subgroup analysis it's worthy
- 36:12of note that they did notice
- 36:14increased local regional recurrence.
- 36:16In high grade tumors,
- 36:18with the Hypo frac with 15.6% of
- 36:21patients who received with with high
- 36:24grade tumors that had hypo fact
- 36:27experience in local regional recurrence
- 36:29versus 4.7 in the 50 Gray arm.
- 36:32However,
- 36:33I will say that start B did look
- 36:35at that and did not find any any
- 36:39difference in outcomes for the
- 36:41Grade 3 tumors,
- 36:42so we tend to still treat those patients
- 36:45with moderate hypofractionation
- 36:46an in the Canadian trial,
- 36:48there was no significant difference
- 36:51in acute toxicity or cosmetic outcome.
- 36:54So maybe we can tighten things up
- 36:56a little bit more now and the newer
- 36:58regimens that are being brought out
- 37:01there are now called Ultra Hypofractionation.
- 37:03And these once again are in for the
- 37:06setting of whole breast radiation only.
- 37:08We are not yet talking about
- 37:11anything with the nodes.
- 37:13And we have two regiments,
- 37:15the fast regimen and the
- 37:17Fast forward regimen.
- 37:18Yale has adopted the FAST regimen which
- 37:20we've been using with great success.
- 37:23We've been very happy with it.
- 37:25We started using it in the fall of last year,
- 37:29so in the fast trial.
- 37:31Patients were randomized to one fraction
- 37:34of radiation per week to a total of
- 37:3828.5 Gray or to a total of 30 Gray,
- 37:41so that's 5.7 or 6 Gray once a
- 37:43week versus the more traditional
- 37:4650 Gray in the 25 fractions.
- 37:48This fast trial is randomized.
- 37:50It's well done,
- 37:52and it has 10 years of follow
- 37:55up at this point,
- 37:56and there was no significant difference
- 37:59in normal tissue affects in the 28.5 by
- 38:03ARM compared to the standard fractionation.
- 38:05And that's why I put that in.
- 38:07Read up there because that is really the arm
- 38:10that we are treating on in the 28.5 Gray arm,
- 38:13because the 30 Gray arm did have
- 38:15increase in normal tissue effects,
- 38:17so we're not using that.
- 38:19For all three dosing fractionation schemes,
- 38:21however,
- 38:21local regional recurrence,
- 38:23distant recurrence,
- 38:23and overall survival were equivalent,
- 38:25and this regimen has made it
- 38:28into the national guidelines.
- 38:29Now the NCC N guidelines saying
- 38:31that it may be considered for
- 38:33patients greater than 50 years of
- 38:36age with early stage breast cancer,
- 38:39which they have defined as as
- 38:41insight to T1T 2AN OI kind of put
- 38:44in that who do not require a boost,
- 38:47they had a few sentences about how boosted.
- 38:50Difficult in this setting and
- 38:52hasn't been established,
- 38:53but that's really how we
- 38:55are approaching it at Yale.
- 38:56If we have a patient with early stage
- 38:59cancer who does not require a boost,
- 39:01and we're not quite ready for patients
- 39:04as young as 50 with just such a
- 39:06short term follow-up of 10 years,
- 39:08so we are tending to lean
- 39:11towards patients 65 and over.
- 39:13Although if someone did have a a
- 39:16needed transportation need or something
- 39:18that still fit this requirement,
- 39:20we would be open for that.
- 39:22The Fast forward has not.
- 39:24It is not yet widely adopted because
- 39:27the data is only going out for five
- 39:31years at this point and that is
- 39:34looking at 26 or 27 Gray in five
- 39:37fractions just Monday through Friday.
- 39:39You're done in a week versus
- 39:41the what's now the more modern.
- 39:44Standard,
- 39:44then the modern standard hypo fractionation,
- 39:4740 Gray, and in 15 fractions.
- 39:49The five year data is promising.
- 39:51It's showing non inferiority
- 39:53and local control.
- 39:54There are increased normal tissue
- 39:56affects with the 27 Gray arm.
- 39:58So overtime I think we're going
- 40:01to be very interesting to see what
- 40:03happens with that 26 Gray arm.
- 40:05And if we get more data,
- 40:08more longer term data under our belt,
- 40:10that may be something that
- 40:12we will be adopting.
- 40:14In the future,
- 40:15that would certainly be very convenient.
- 40:20So, so far we've only talked about
- 40:23using the HYPOFRACTIONATION in settings
- 40:26where just the breast is being treated.
- 40:28What about in the setting of
- 40:31regional nodal or radiation,
- 40:33or post mastectomy radiation therapy?
- 40:35There is a growing body of maturing
- 40:38data and accruing data in this
- 40:40setting that we may see in the future
- 40:43that we are more widely adopting.
- 40:46The hypo fractionation for
- 40:48these patients as well.
- 40:49One trial that's ongoing right
- 40:52now is the RT charm trial.
- 40:54And it's looking at moderately
- 40:57hypofractionated post mastectomy
- 40:58radiation therapy for patients who've
- 41:01had breast reconstruction comparing
- 41:03with the standard 50 Gray and patients
- 41:06can have autologous reconstruction
- 41:09implant reconstruction immediate
- 41:10or delayed to be on this trial.
- 41:15The fabric trial that is open at
- 41:18Yale Dr Mina Moran is RPI for that.
- 41:22That's the study of radiation
- 41:24fractionation on patient outcomes
- 41:26after breast reconstruction
- 41:27for invasive breast cancer,
- 41:29and this is randomized as
- 41:32well to hypofractionation.
- 41:33Plus,
- 41:33the more standard 50 Gray and
- 41:36patience for this would have
- 41:38permanent implant or tissue expander.
- 41:41This is not for autologous patients.
- 41:43There is some published data.
- 41:46That one can find,
- 41:47for example,
- 41:48this trial out of China by Doctor Wang.
- 41:51It's a randomized trial of standard
- 41:54fractionation versus moderately
- 41:55hypofractionated patients in post
- 41:57mastectomy radiation therapy.
- 41:58I read every word in the article.
- 42:00I can find nothing that really
- 42:03discuss is if reconstruction was
- 42:05used and the median follow-up
- 42:07is not that long at 58.5 months,
- 42:09but there is an.
- 42:11These were a little bit high.
- 42:13These were some high risk patients as well.
- 42:17Four or more involved nodes
- 42:18for everybody T3T4,
- 42:20but there was no difference in local
- 42:22regional recurrence between the 50
- 42:24Gray in the moderate hypofractionation,
- 42:26but there was an increase
- 42:27in grade 3 acute toxicity,
- 42:29in the Hypo frac arm,
- 42:31so none of this has really LED for
- 42:33wide adoption of the of hypo frack in
- 42:36the setting of treating regional nodes
- 42:38or post mastectomy radiation therapy.
- 42:41At this point I have done
- 42:43it in very select patients.
- 42:45I think that the rest of our.
- 42:47Group has but it has not yet been
- 42:50adopted by the NCC N due to the
- 42:52paucity of data at this point.
- 42:54Although overtime,
- 42:55I'm sure that charm and fabric will
- 42:57provide us with a lot of information.
- 43:02OK. So, another way,
- 43:05besides shortening the treatment course
- 43:07in the number of visits is by decreasing
- 43:10the volume of tissue that we are treating.
- 43:13One way that's been around for awhile.
- 43:16Actually, you post all probably know,
- 43:18is accelerated partial breast
- 43:20irradiation therapy,
- 43:20and until recently there was a
- 43:22lack of longer term phase.
- 43:24Should say phase three up there
- 43:27scuse me of longer term phase
- 43:30three data supporting a PBI.
- 43:32We do have these two studies that I put
- 43:35up here that now are have randomized
- 43:38data giving us their ten year outcomes.
- 43:41The NSA BP.
- 43:4239 that looked at whole breast
- 43:44irradiation with standard frack versus
- 43:47accelerated partial breast irradiation
- 43:49therapy using either breakey therapy or
- 43:51external beam twice a day for 10 fractions.
- 43:54So patients would be done in a week.
- 43:57It's very interesting results,
- 43:59so they were really looking
- 44:01at in ipsilateral.
- 44:02Breast tumor recurrence.
- 44:03At 10 years it was found to be
- 44:074% and the accelerated partial
- 44:08breast irradiation and 3% in the
- 44:11whole rest of radiation arm.
- 44:13But based on their statistical analysis,
- 44:15even though there's just that 1% difference,
- 44:18it did not meet the criteria for equivalence,
- 44:21so API was not bound to be equivalent
- 44:24to whole breast or radiation therapy.
- 44:27That being said,
- 44:28in the discussion the authors
- 44:30discuss how with that 1% difference
- 44:32in lower risk patients.
- 44:34This still does perhaps leave the door
- 44:37open for a PBI for for low risk patients.
- 44:41The Florence trial.
- 44:42He has gained a lot of attention
- 44:44and that has treated accelerated
- 44:46partial breast irradiation therapy.
- 44:48So when we're trading with accelerated
- 44:50partial breast radiation therapy,
- 44:51you probably all know that we are really
- 44:54concentrating the radiation therapy
- 44:56on the tumor bed and an expansion,
- 44:59and therefore we are leaving
- 45:00more of the well.
- 45:02We're leaving the uninvolved breast
- 45:04or a good portion of the uninvolved
- 45:07rest out of the high dose area.
- 45:09And by tightening our fields
- 45:11like this one can.
- 45:12Also.
- 45:15Less dose to the healthy tissues as well,
- 45:19so the Florence trial used accelerated
- 45:21partial breast radiation therapy
- 45:2330 Gray and five fractions using
- 45:25and I MRT approach versus whole
- 45:27breast and standard fractionation.
- 45:29So at 10 years with their randomized trial,
- 45:33there was no significant difference in
- 45:35ipsilateral breast tumor recurrence.
- 45:37It was 2.5% in the whole breast
- 45:40versus 3.7% in the accelerated
- 45:42partial breast irradiation therapy.
- 45:43But based on their statistical analysis,
- 45:46this was not.
- 45:47Statistically different,
- 45:48there was also significantly less
- 45:50acute in late term toxicity with the
- 45:53accelerated partial breast radiation therapy,
- 45:55so they partial breast irradiation therapy
- 45:58has made it into the national guidelines.
- 46:01It's been there for a little while,
- 46:04but on the most recent iteration,
- 46:07the Florence Regiment is listed
- 46:09as the preferred regimen,
- 46:11and it is recommended that the
- 46:14Astro guidelines where I've put
- 46:16a reference on here.
- 46:18As many of you may know,
- 46:21Astro has published guidelines regarding
- 46:23who is suitable for accelerated
- 46:26partial breast irradiation therapy,
- 46:28and there are three groups,
- 46:31suitable cautionary and basically
- 46:33do not treat unsuitable.
- 46:36So here at Yale, we are working.
- 46:39We do treat accelerated partial
- 46:41breast irradiation therapy.
- 46:42Although not very often for suitable cases,
- 46:45just because the hypo frack is so
- 46:47works out so well and you're really
- 46:50not saving the patient much time.
- 46:52However, we are in the process
- 46:54of gearing up to start offering
- 46:57treatment in the manner that
- 46:58was used in the Florence trial,
- 47:01the 6th grade Perfection Times 5
- 47:03fractions and that was every other day.
- 47:06Using I MRT.
- 47:07So we are working with our physics
- 47:09department and doing all the safety
- 47:11checks and getting our policies and
- 47:13procedures in place to start adopting that.
- 47:15But we are not on line for that just yet.
- 47:21So what about decreasing our the
- 47:24amount of tissue that's treated in the
- 47:27setting of regional nodal irradiation?
- 47:30Well, there is some ongoing trials that
- 47:33we read before this is widely adopted
- 47:35to start eliminating our nodal fields.
- 47:38In certain cases we need some
- 47:40more guidance on that in,
- 47:42especially in the post mastectomy
- 47:44setting you know who who,
- 47:46when the patients have involved,
- 47:48knows, who can we really skip treating
- 47:50the regional nodes and still ensure
- 47:53that we have excellent outcomes?
- 47:55This trial, the NSA BP 51 it was
- 47:58open at Yale for a while and it
- 48:01was very challenging to accrue to,
- 48:04and it was nationally quite difficult to
- 48:07accrue too so really long trial may not name.
- 48:11Maybe that was part of it that it's a bait.
- 48:15You can read the name there,
- 48:17but basically what it does is it
- 48:19took patients who had pathologically
- 48:22proven by biopsy,
- 48:23axillary nodal involvement who received.
- 48:25Neoadjuvant chemotherapy.
- 48:26Then they would undergo either
- 48:29lumpectomy or mastectomy.
- 48:30And they could have Sentinel
- 48:33lymph node biopsy,
- 48:34Sentinel lymph node biopsy converted
- 48:36to XI section or XI section.
- 48:39But if they were converted to YPN 0
- 48:43then these patients were eligible.
- 48:46Remember,
- 48:46they had to have T1T3 pathologically
- 48:49proven N1 disease upfront,
- 48:51neoadjuvant, chemo,
- 48:52and then rendered YPNO in the axilla.
- 48:56So arm one was omission of
- 48:58regional nodal irradiation therapy,
- 49:00with so lumpectomy patients would only
- 49:02have the breast treated high tangents.
- 49:05Not allowed.
- 49:06Mastectomy would have no radiation.
- 49:08An arm two,
- 49:09which was I call it the yes regional
- 49:11nodal radiation therapy would treat
- 49:14in though that arm the whole breast
- 49:17and the chest wall would receive
- 49:20radiation plus regional nodal
- 49:22irradiation which was defined on
- 49:24the trial as internal mammary nodes.
- 49:27Une dissected axilla.
- 49:30And the superclass.
- 49:30So you're either getting a very
- 49:32limited radiation or basically the full boat.
- 49:34And I think that some people
- 49:36when I mean I know when I talk
- 49:38to patients about the trial one,
- 49:40either want they either
- 49:41wanted one arm or the other,
- 49:43and many people were reluctant to let go
- 49:45of the regional nodal radiation therapy.
- 49:47So I personally was not able to accrue
- 49:50anyone to the trial when I spoke with them.
- 49:52And I think that that was a
- 49:54problem kind of nationwide,
- 49:56but it's now closed to accrual.
- 49:57They've obviously reached their goal,
- 49:59which is great.
- 50:00And I am not aware of any
- 50:03preliminary results at this time.
- 50:06Another trial this is open at
- 50:09Yale and we are actively accruing.
- 50:11So please we would love to have
- 50:14your patience on this trial.
- 50:16The MA 39 also called Taylor RT.
- 50:19This is different.
- 50:20This is not really looking at
- 50:22response to chemotherapy.
- 50:24It is looking at omitting regional
- 50:26nodal radiation therapy for patients
- 50:28who have a more favorable cancer as
- 50:31far as biomarker risk is concerned.
- 50:33So the and the inclusion criteria.
- 50:36Changed extremely recently within
- 50:37the last eight weeks.
- 50:39Initially when we open the trial,
- 50:41only T1 or T2 patients were
- 50:43allowed on the trial,
- 50:45but now patients with T3 disease are allowed.
- 50:48Also, a very recent change and what the
- 50:51definition of low volume nodal disease.
- 50:53What is this? Is the updated version here,
- 50:56so if the patient had lumpectomy
- 50:58or mastectomy an axe dissection,
- 51:00they can have one to three positive
- 51:02nodes if they have lumpectomy
- 51:04or mastectomy plus Sentinel.
- 51:06Lymph node biopsy only.
- 51:07They can now have one to two positive nodes.
- 51:10That's a change.
- 51:11And a huge change is that the archetype
- 51:14score when this trial opened had to
- 51:17be 17 or less to enroll patients.
- 51:21Now patients with an archetype score
- 51:23of 25 or less our are eligible.
- 51:26They cannot have had neoadjuvant
- 51:28chemotherapy.
- 51:28They've also made it amendment allowing
- 51:31for they are allowing for neoadjuvant.
- 51:33I should have said Neo there,
- 51:36excuse me.
- 51:37Neoadjuvant endocrine therapy is now allowed.
- 51:41Agement chimos allowed.
- 51:42Agement endocrine therapy is allowed.
- 51:44Patients are randomized,
- 51:45similar to the other one.
- 51:47The no regional nodal radiation
- 51:49arm that no RNI,
- 51:51so those patients would have to have whole
- 51:54breast irradiation if they had lumpectomy,
- 51:56but no radiation.
- 51:57If mastectomy and then yes,
- 51:59are in,
- 52:00I would be whole breast irradiation
- 52:02or chest wall irradiation depending
- 52:04on their surgery and regional nodal.
- 52:07And like the other trial,
- 52:09regional nodal means internal mammary nodes.
- 52:11Une dissected axela in the superclass.
- 52:15And the primary endpoint is breast
- 52:17cancer recurrence free interval,
- 52:19but of course they're over looking at.
- 52:22You know, local recurrence,
- 52:24distant recurrence, side effects,
- 52:25and lymphoedema risk as well.
- 52:30So the last way to limit or deescalate the
- 52:34radiation therapy is to just not do it.
- 52:37That's the kind of most straightforward.
- 52:39I think that a lot of us now are
- 52:42familiar with the CL GB 9343 trial.
- 52:45I can, you know,
- 52:47memorize this one in my sleep.
- 52:49Those patients were 70 years
- 52:51of age or older T1 tumors.
- 52:53They could be clinically or
- 52:55pathologically node negative had
- 52:56to be hormone receptor positive and
- 52:59lumpectomy with negative margins.
- 53:01I put the negative margins in red
- 53:03because for this trial negative
- 53:05margins was defined as no tumor on Inc.
- 53:09The patients were randomized to
- 53:11tamoxifen alone or whole breasts or
- 53:13radiation therapy using a moderate
- 53:16hypofractionation course plus tamoxifen.
- 53:18At 10 years you could see the overall
- 53:21survival was the same 67% in Tamar T
- 53:24and 66% in the Tam arm with a lot of
- 53:28those deaths being non breast cancer
- 53:30deaths and freedom from local regional
- 53:33recurrence was 98% in the Tamar TR man,
- 53:3790% in the Tamar that actually
- 53:39was statistically significant,
- 53:40there was a statistically significant
- 53:42reduction in the risk of local regional
- 53:45occurrence with the radiation being provided.
- 53:48So you might say, well,
- 53:50this trial should support us doing
- 53:52the radiation,
- 53:53but because the overall survival
- 53:55was not different and although
- 53:57I don't have it up there,
- 53:59the very low rate of distant
- 54:01recurrence was no different.
- 54:02The breast cancer specific
- 54:04mortality was not different,
- 54:05so the radiation was not doing
- 54:07anything to prevent those more.
- 54:09One could argue more meaningful outcomes.
- 54:11So this could.
- 54:12This is used for two in support
- 54:14of omitting radiation therapy for
- 54:17women that meet the criteria.
- 54:19If I see patients and I have a 71
- 54:21year old patient who is very who I
- 54:24feel has a life expectancy exceeding
- 54:2610 years or then we talk about hey,
- 54:29maybe we should do the radiation so.
- 54:32But it is good fodder for discussion
- 54:34and an it can help to find those
- 54:37patients for whom a mission of radiation
- 54:40therapy would be certainly acceptable.
- 54:42Also,
- 54:43patients are not going to
- 54:44take the endocrine therpay.
- 54:46They really should get the radiation.
- 54:48Prime two is similar.
- 54:50It's a little bit behind as far
- 54:52as how long it's been accruing
- 54:54and following out the data.
- 54:56The women can be 65 or older,
- 54:59T2 tumors up to three CM.
- 55:01They must have pathologically
- 55:03negative nodes with Sentinel node
- 55:04biopsy or XI section hormone receptor
- 55:07positive and their definition of a
- 55:09negative margin is 1 millimeter.
- 55:10They live had some limits that
- 55:13the CL GB trial did not.
- 55:15The tumor could be grade 3 or have elvii,
- 55:18but you could not have.
- 55:20Both an once again must have
- 55:22adequate their Bay and we see
- 55:24similar results at the five years.
- 55:26It almost mirrored the CLG be at
- 55:28the five years where ipsilateral
- 55:30breast tumor recurrence was around
- 55:321% in the radiation arm and 4%
- 55:35in the no radiation arm with no
- 55:37difference in overall survival.
- 55:39There was a recent update
- 55:40at the San Antonio Breast
- 55:42Conference, however, that paper has
- 55:44not followed showing similar results
- 55:46as CLG be at 10 years with ipsilateral
- 55:49breast tumor recurrence around 10.
- 55:51In the know in the, I miss those up in
- 55:55the no RT arm and then .9% in the RT arm.
- 55:58So I think that Prime 2 once
- 56:01that paper comes out,
- 56:03you know we may start offering for younger
- 56:06women or women with some larger tumors.
- 56:08Omission of radiation therapy.
- 56:11Now this is my last slide before I get
- 56:14into the thank yous in the summaries,
- 56:17and these are trials that
- 56:18I'm not that familiar with.
- 56:20To be frank with you,
- 56:22there seemed to be more surgical trials,
- 56:24but I thought they were worth
- 56:26just springing up.
- 56:27We have the comet trial open at Yale.
- 56:30The Pi is doctor Golshan,
- 56:31and that if I'm understanding correctly,
- 56:33looks at.
- 56:34You know what's considered a lower
- 56:36risk DCIS grade one and grade two and
- 56:39looking at endocrine therapy alone
- 56:40with surveillance in lieu of surgery,
- 56:42an obviously,
- 56:43if we don't do surgery.
- 56:45We're not coming to the radiation,
- 56:47so in a way this would be part of
- 56:49omitting radiation and the Lord
- 56:51trial is somewhat similar as well.
- 56:53I'm for my homework.
- 56:54I feel I need to learn a little
- 56:56bit more about these trials,
- 56:58so I'll give you guys some homework too,
- 57:01but I felt that it would not be
- 57:03complete without bringing it up,
- 57:05but I think it's interesting
- 57:06you know the question that seems
- 57:08to be being asked if I'm is,
- 57:10can screen detected low risk
- 57:11DCIS be managed by an active
- 57:13surveillance strategy rather than.
- 57:15Surgery.
- 57:15So in summary,
- 57:16we are seeing you know in real
- 57:19time and working further towards a
- 57:22deescalation of radiation therapy for
- 57:24appropriate patients in regard to
- 57:26the number of treatment visits infractions,
- 57:29the volume of tissue treated,
- 57:31and the appropriate emission
- 57:32of radiation therapy,
- 57:33and I'd like to thank you if you
- 57:36have any questions about any of the
- 57:38references or would like to discuss further.
- 57:42That's my contact info,
- 57:44thanks.
- 57:45Thank
- 57:45you so much Doctor Knowlton wow
- 57:47three really fantastic talks and I
- 57:50really appreciate everyone's time and
- 57:51effort in our audience for listening
- 57:54and putting in some questions.
- 57:56Please feel free to put in.
- 57:58More questions will be happy to answer
- 58:01them and while we wait for those I have
- 58:04a couple just listening to the talks.
- 58:06Maybe I'll start with Doctor, Doctor
- 58:09Hooley and a little bit about the contrast.
- 58:12Enhance image Ng for screening and
- 58:14how you can do that without contrast.
- 58:16Potentially I was.
- 58:20You know like more,
- 58:21but you know you know where we're
- 58:24at in the United States and maybe
- 58:27where we're going and
- 58:28be great to hear about that.
- 58:31Sure, so uh, MRI has shown that
- 58:33contrast enhanced screening has the
- 58:36highest cancer detection rate, right?
- 58:38So because cancers are vascular,
- 58:40and so you know,
- 58:41that's the way it's going with contrast,
- 58:44enhanced mammography,
- 58:45and even like in the breast
- 58:48imaging which all require.
- 58:49You know Ivy contrast.
- 58:51There are some studies looking at
- 58:53MRI and diffusion weighted images,
- 58:56or some people who say that
- 58:58they will never happen.
- 59:00Some people say that it will
- 59:03perhaps somehow happen that you
- 59:05could do MRI with diffusion,
- 59:07weighted imaging or some other technique
- 59:10that some really smart people are
- 59:12going to invent and figure out some
- 59:15some sequences where we can look at
- 59:18vascularity without Ivy contrast injection.
- 59:20Likewise, there are also some
- 59:23ultrasound products out there.
- 59:25Randy Butler participated in
- 59:27an auto acoustics ultrasound
- 59:29study that was the optoacoustic.
- 59:32Ultrasound equipment was just
- 59:33FDA approved last January and
- 59:36it's basically looking at heating
- 59:38lasers and heating lights.
- 59:40Laser light and heating the blood
- 59:43vessels and looking determining
- 59:45oxygenation within the blood vessels.
- 59:48And she published a couple of articles.
- 59:51Common radiology,
- 59:52which is our top journal showing
- 59:54the vascularity within tumors
- 59:56and superimposing that over a
- 59:58traditional ultrasound so that
- 60:00is vascular based without without
- 01:00:01contrast and there's some other.
- 01:00:05New ultrasound techniques.
- 01:00:06Also that are a little bit
- 01:00:08different that measure.
- 01:00:09They can measure vascularity as well,
- 01:00:11so those are the ones that right now are.
- 01:00:16Active you know, and we could see it.
- 01:00:18You know,
- 01:00:18in five or ten years or maybe sooner.
- 01:00:20Who knows.
- 01:00:21Well,
- 01:00:21actually opt acoustics is already out there,
- 01:00:23so you have to wear fancy
- 01:00:25space classes and stuff.
- 01:00:27Awesome,
- 01:00:27thank you a question for Doctor Abraham.
- 01:00:30What are some of the signs or
- 01:00:32indications that you know clinicians
- 01:00:34out there should be aware of,
- 01:00:37for you know for those that end up
- 01:00:39getting implants for reconstruction
- 01:00:41with the implant associated anaplastic
- 01:00:43large cell lymphoma, which is, you know,
- 01:00:47gotten some press in the last year or two.
- 01:00:51Dial yeah, so first of all the the presence
- 01:00:54of a textured implant which is obviously
- 01:00:56for somebody who's not a plastic surgeon.
- 01:00:59Maybe a little bit challenging.
- 01:01:01So if there's any concern you know,
- 01:01:03have the patient go back to the plastic
- 01:01:05surgeon so you know because we are at
- 01:01:08this point considering removing them
- 01:01:10sort of prophylactically and then any change,
- 01:01:13particularly a delayed ceroma,
- 01:01:14is what is classically referred to.
- 01:01:16So you know in in breast surgery
- 01:01:18seromas are not uncommon,
- 01:01:20but you know, at the time of
- 01:01:22surgery or immediately following.
- 01:01:24Postmastectomy radiation,
- 01:01:25but if there is a saroma that develops
- 01:01:30and delayed fashion to 310 years after an
- 01:01:33implant is placed at sign for concern.
- 01:01:36Thank you and maybe a last question.
- 01:01:39For doctor Knowlton.
- 01:01:40You know, I I,
- 01:01:41you know,
- 01:01:42often we see patients that are over
- 01:01:44the age of 70 small your positive
- 01:01:47breast cancers and you know with
- 01:01:49the LGB data that you showed you
- 01:01:52know undergoing breast conservation
- 01:01:53and forgoing radiation and you
- 01:01:55know doing anti estrogen therapy.
- 01:01:57But have you also seen the converse
- 01:01:59where some would just prefer to do a
- 01:02:01short course of radiation as opposed
- 01:02:03to putting themselves through?
- 01:02:05You know 5 plus years of anti
- 01:02:08estrogen therapy.
- 01:02:09I guess like if we bias a patient one
- 01:02:12way or the other when they get to you,
- 01:02:14how is that
- 01:02:15discussion go that I see this every week?
- 01:02:18I would say every week.
- 01:02:19So and you know, I listen to the patient.
- 01:02:22Many of them come in with some biases
- 01:02:25against the endocrine therapy.
- 01:02:27So that doctor Google doesn't do
- 01:02:30endocrine therapy much justice.
- 01:02:31So I talked to them about data showing
- 01:02:34that you know at least half of
- 01:02:36patients really don't get any of these.
- 01:02:39You know, join aches or hot
- 01:02:41flashes and that's placebo.
- 01:02:42Patients got the same amount.
- 01:02:44Maybe they should just give it a try.
- 01:02:47I discussed the benefit of helping prevent
- 01:02:49breast cancer in the contralateral breast.
- 01:02:52An IV after I finish my spiel,
- 01:02:54it's attempting to get them to be
- 01:02:57more open to AI or.
- 01:02:59Tim, sometimes they will try it
- 01:03:00and we'll check back in with each
- 01:03:03other in two to three months.
- 01:03:04And if they're still taking it in,
- 01:03:06tolerating it super,
- 01:03:07or if they're not,
- 01:03:08then I have come back and done the
- 01:03:11radiation at that point or even,
- 01:03:12or some if they might give my
- 01:03:15initials feel an they still tell
- 01:03:17me I'm not by I'm not going to
- 01:03:19take it no matter what I say, OK,
- 01:03:21I hear you and then we would either.
- 01:03:23Do you know?
- 01:03:24Depending on the characteristics of the
- 01:03:26tumor and the patients comorbidities,
- 01:03:28we may do a fast regimen of once a week,
- 01:03:31or you may do the moderately hypo frack.
- 01:03:33The 15.
- 01:03:34Plus or minus a boost,
- 01:03:35so I certainly do see that that
- 01:03:37quite quite often every week.
- 01:03:40Ann and maybe just to finish off on on
- 01:03:42that when they you said maybe try anti
- 01:03:45estrogen therapy for a month or two.
- 01:03:47Is there kind of a cut off where you
- 01:03:50would say that if they went with
- 01:03:52anti estrogen and decided to stop
- 01:03:54and wanted to come back to you to
- 01:03:56radiation where you'd feel comfortable.
- 01:03:59Well, that's a good question.
- 01:04:00You know two or three months
- 01:04:02I wouldn't even blink an eye,
- 01:04:04especially if they were taking
- 01:04:05endocrine therapy for the bulk of
- 01:04:08that I have done up to six months.
- 01:04:09I have done it, but at that point we
- 01:04:12may ask the patient to have another
- 01:04:14Mamo before starting the radiation.
- 01:04:16And sometimes I'll bring those patients
- 01:04:18up in our multidisciplinary tumor board.
- 01:04:19I did have one patient where it was a
- 01:04:22year out, but she was substantially high.
- 01:04:24Risk enough that I presented,
- 01:04:26or at our multidisciplinary
- 01:04:27tumor board we got.
- 01:04:29Breast imaging no evidence that not.
- 01:04:31There's nothing suspicious on that,
- 01:04:33and I did offer radiation,
- 01:04:34but beyond six months I would really
- 01:04:36want to have a multidisciplinary
- 01:04:38discussion about that.
- 01:04:41Thank you and again thank you all
- 01:04:43so much for these three wonderful
- 01:04:45presentations I I learned so much
- 01:04:47in the course of the last hour and
- 01:04:50a half and the great thing is that
- 01:04:52this is recorded so others could go
- 01:04:54back and be able to look at that.
- 01:04:57Really thank the audience for
- 01:04:58joining us for this series of three
- 01:05:00breast CME's here at Yale and and
- 01:05:02look forward to continuing them
- 01:05:04in the next academic year.
- 01:05:06So with that thank you so much.
- 01:05:08Have a great weekend. Thank
- 01:05:09you, thank you.