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Today we are on our to welcome Dr. Rachel brem for

0:46

a lecture on high-risk breast lesions.

0:49

Dr. Brim is a vice chair and professor

0:52

of radiology at the George Washington University School of

0:55

Medicine and Health Sciences as well as the Director of

0:58

breast Imaging and Interventional Center.

1:00

She has been instrumental in the FDA clearance and

1:03

introduction of numerous breast cancer Technologies and has published

1:06

more than 100 Journal 100 Journal articles

1:09

and manuscripts related to breast cancer, Dr. Bramas

1:12

also the medical director in co-founder of

1:15

the brim Foundation to defeat breast cancer, which is

1:18

dedicated to education advocacy and Care

1:21

in the underserved community and as a breast cancer survivor

1:24

herself, she understands and is committed to the science and

1:27

a personal aspects of breast cancer.

1:29

We are grateful for Dr. Brim and her support of MRI

1:32

online and for serving as our breast Imaging so specialty

1:35

advisor. We have learned so much from you.

1:38

At the end of the lecture, please join Dr. Brim in a Q&A

1:41

session where she will address any questions you may have on today's topic. Please

1:44

remember to use the Q&A feature to submit your

1:47

questions and get to as many as we can before our time is up.

1:50

With that being said we are ready to begin today's lecture

1:53

Dr. Brim. Please take it from here.

1:56

Hi, thank you very much for that lovely introduction. I'm

1:59

delighted to be here today with the

2:02

participants in this MRI online very appropriate

2:05

that we're discussing breast cancer as we

2:08

close out breast cancer awareness month and what we're

2:11

going to talk about today is minimally

2:14

invasive high-risk

2:17

lesions.

2:20

Sorry, great. So, let me just

2:23

get organized here.

2:26

Terrific, so we're going to talk about minimally invasive breast

2:29

biopsy with high risk lesions and what

2:32

to do about them.

2:36

So this is my disclosures.

2:40

Some okay.

2:46

And really they're two types two categories

2:49

of high-risk lesions lesions that are found

2:52

at minimally invasive breast biopsy that have a significant

2:55

risk of demonstrating cancer or upgrade at

2:58

surgical excision and lesions that indicate an

3:01

increased risk of a woman developing breast breast

3:04

cancer during her lifetime. Now, we're

3:07

going to talk about a number of high-risk lesions including

3:10

atypical ductal hyperplasia papillary lesions

3:13

radial score scar flat at

3:16

the philhealatypia. We're going to talk about lobular neoplasia.

3:21

Um, including both a typical lobular hyperplasia and

3:25

lcis lobular carcinoma and situ and

3:28

we're going to talk about mucus here like lesions.

3:34

one second to

3:36

Great.

3:40

Okay, so let's talk about breast cancer

3:43

risk with these different lesions and if we talk about the general population

3:46

where the relative risk of developing breast cancer

3:49

is one or twelve percent of the American women

3:52

developed breast cancer by the age of 80. If

3:55

you look at flat at the theliolate tipia the

3:58

risk the relative risk is about 1.5 that

4:01

with papillary lesions particularly those with

4:04

atypia. It's about twice that radial scar

4:07

similar to papillary lesions and atypical ductal

4:10

or lobular hyperplasia about a four-fold relative risk

4:13

of developing breast cancer and lobula carcinoma

4:16

in situ very significantly higher with about

4:19

a tenfold increase risk of developing breast

4:22

cancer with the absolute risk of

4:25

developing breast cancer of 1% per year which translates

4:28

to about 20% at 20 years.

4:32

So really what we want to talk about is the key to

4:35

how to understand which lesions that are found

4:38

at minimally invasive bit breast biopsy requires

4:41

surgical excision. And the reason we excise

4:44

them is to rule out the adjacent cell

4:47

being malignant and that's what upgrade is

4:50

and sometimes certainly the

4:53

issue of whether excision results in

4:56

decreasing the risk of developing breast cancer in the future the

4:59

likelihood of that is probably not but one

5:02

of the things it's very important is that the method that of acquisition of

5:05

the tissue is extremely important and we'll

5:08

talk about that now some more and

5:11

we're also going to talk about some pharmacologic approaches

5:14

to prevent or decrease

5:17

the risk of breast cancer.

5:20

So at minimally invasive breast biopsy that is the standard

5:23

of care and our institution and many that are

5:26

joining us today a hundred percent of the breast

5:29

biops are breast biopsies are done minimally invasively.

5:32

The reason is that it's very low cost very

5:35

low morbidity. Excellent patient

5:38

acceptance great cosmetic outcome, but

5:41

the less tissue you get the less

5:44

complete sampling of the lesion occurs,

5:47

and as a result of not exciting the entirety of

5:50

the lesion, there is some heterogeneity of lesions and

5:53

therefore lesions that have high risk findings

5:56

that pathology at minimally invasive

5:59

but best biopsy require surgical excision to

6:02

exclude the heterogeneity of an adjacent

6:05

malignant cancer.

6:07

So if you look at the upgrade rate at

6:10

minimally invasive or percutaneous biopsy, you

6:13

can see that it really varies and

6:16

I think this is the Crux of much of

6:19

the uncertainty of how to deal with these lesions.

6:22

And that is you can see that the upgrade rate of

6:25

ADA ranges from 13 to 31 percent

6:28

the upgrade rate for papillary lesions with atypia

6:31

ranges from 10 to 37 percent

6:34

and as we'll see more recent studies of

6:37

shown that the upgrade rate of papillary lesions without a

6:40

tibia is really zero percent. So perhaps we

6:43

can follow those and we'll talk more about that later flat at

6:46

the filial a tip you the upgrade rate is eight to

6:49

fourteen percent a typical lobular hyperplasia. Hugely

6:52

variable right from 0 to 22 percent

6:55

depending on the study and lcis 4

6:58

to 25% Now, I really want to

7:01

point out a number of things one is that most of

7:04

these are single institution studies the other

7:07

Is that there's great variability in the number of

7:10

cases. So here you can see with adh422 cases

7:13

versus 40 cases a hundred

7:16

and twenty-five cases versus 38 cases,

7:19

but regardless of what you

7:22

see regardless of what study with few exceptions the

7:25

numbers are very small hence the

7:28

variability and upgrade at surgical excision and

7:31

something that I'll deal with a bit later which

7:34

is the need for multi-institutional study. And

7:37

the reason there's variability is because the small sample

7:40

size in the studies and it's really also important

7:43

to understand that the biopsy device that used really

7:46

impacts. The upgrade rate. There is an inverse

7:49

relationship between the upgrade rate and the amount of tissue obtain.

7:52

So a lot of tissue less upgrade smaller

7:55

cores less tissue

7:58

higher upgrade, right and also to understand

8:01

that in the pathology literature, there's a great deal of

8:04

variability.

8:06

And what is alh versus lcis? What

8:09

is ADH versus dcis and

8:12

there have been quite a few studies that have

8:15

shown that if you send the same slide of

8:18

For example ADH to 10 different Pathologists,

8:21

you will get a variability in

8:24

whether they consider it ADH and dcis

8:27

and that's actually quite astounding because the

8:30

consequences to the patient the treatment

8:33

the follow-up the implications from a

8:36

management standpoint are really enormous. If

8:39

a patient has dcis versus a ADH,

8:42

you know ADH is a high risk marker

8:45

dcis is a woman with breast cancer. So and understanding

8:48

that the variability of pathologic diagnosis on

8:51

the part of pathologist is great. Really I think

8:54

sheds light on the difficulty of these lesions, so

8:58

Here you can see normal cells introductal hyperplasia

9:01

too many normal cells

9:04

a typical introductal hyperplasia numerous cells

9:08

with some atypia then dcis and

9:11

then of course the basement membrane is violated and

9:14

then you have an infiltrating ductal carcinoma. So the

9:17

question is which one of these do we need to excise do we

9:20

need to excise atypical doctor hyperplasia and dcis

9:23

do we have to excise introductal hyperplasia

9:26

and ADH so interestingly quite

9:30

some time ago. Now the New York Times front page

9:33

also had a question about this but they actually spun

9:36

it quite negatively saying that breast biopsies are

9:39

not full proof. They're not perfect and it

9:42

doesn't leave doubt. It just shows that

9:45

these are high risk deletions that are not cancer, but

9:48

they are abnormal cells

9:51

that require surgical excision and it's important to

9:54

remember that it's a small percentage of the breast

9:57

biopsies that we're doing.

9:59

But more recently there's extension of this to

10:02

dcis. There are a number of clinical trials that

10:05

are ongoing around the country in California a

10:08

Duke asking can we just observe low-grade

10:11

dcis? And so the answer

10:14

to that is not out. I am by no means saying that dcis does

10:17

not need to be excised and treated but we are

10:20

wrestling with that and looking at the data

10:23

very critically to see if that

10:26

in fact might be an approach for some women with low grade

10:29

dcis.

10:30

So again percutaneous biopsy

10:33

does not excise the entirety of the lesion and

10:36

because of the heterogeneity and the clonality of

10:40

cells that you might need surgical excision to

10:43

exclude the adjacency of cancer.

10:47

And it can be very controversial. So now let's

10:50

start by talking about ADH and let's start with that

10:53

because that's actually the easiest and most straightforward of

10:56

the lesions.

10:58

So what ADH is is an epithelial proliferation of

11:01

the terminal duct globular unit with cytologic

11:04

atypia and Architectural changes. So basically

11:07

what it is is it has some but not all of

11:10

the features of dcis.

11:12

So either it can be essentially the

11:15

same as dcis, but three millimeters or less or

11:18

not have all the cytologic features of dcis

11:21

and about five

11:24

to 15 percent of percutaneous breast biopsies

11:27

result in a diagnosis of ADH.

11:30

So again schematically atypical hyperplasia

11:33

is numerous atypical cells

11:36

within the duct and this is what it looks

11:39

like on a pathologic specimen.

11:41

Mammographically at most frequently presents

11:44

as micro calcifications often indistinguishable

11:47

from dcis or

11:50

fibrocystic change their indeterminate

11:53

classifications that require sampling for

11:56

definitive pathologic determination.

11:59

Multiple Studies have shown pathologic underestimation

12:02

of cancers on cornedal

12:05

biopsies that subsequently are found to be ADH and

12:11

All of the Studies have shown significant upgrade, although you can see

12:14

huge variability in the upgrade ranging from 10 to

12:17

56 percent. And the reason this variability exists

12:20

is because the higher upgrade rate is

12:23

associated with smaller needles and the lower upgrade rate

12:26

is associated with larger vacuum assisted

12:29

biopsy devices and in

12:32

a study that was published in 2011 looking at

12:35

the factors associated with upgrade to malignancy when

12:38

ADH is found. You can see here that there

12:41

is substantially higher upgrade rate when the

12:44

14 gauge core needle biopsy is used as compared to

12:47

an 11 gauge vacuum assisted biopsy.

12:50

And atypical hyperplasia upgrade rates.

12:53

Oops, I'm sorry.

12:55

just trying to

12:58

can vary widely from 13% or

13:01

12% to 31% And

13:04

again notice the denominator in

13:07

these studies very variable. So if

13:10

you have one or two additional upgrade rates

13:13

when you're denominators, 40 cases, it can have a

13:16

very significant impact on the upgrade rate.

13:22

Okay, the Imaging modality

13:25

that ADH is found with also influences.

13:28

The upgrade rate Laura Lieberman in 2007 demonstrated

13:31

a very substantial 38% upgrade

13:34

rate of ADH when it was

13:37

found at MRI even with vacuum as a

13:40

large vacuum assisted biopsy needle is used.

13:43

Similarly in 2014 a large Mr. Guided

13:46

biopsy demonstrated a 30% 2% upgrade

13:49

rate for ADH found at MRI.

13:53

And it didn't matter what the lesion

13:56

type was whether it was non-mass or

13:59

mass enhancement the size of the lesion or previous history of breast

14:02

cancer. So what we can see is the upgrade rate of

14:05

ADH is a very complex interaction of the

14:08

type of lesion the type of biopsy device

14:11

and

14:14

and it's very important to see also what

14:17

the guidance method is to biopsy these

14:20

lesions.

14:23

So it's also important to stratify

14:26

risk in women with atypia. And

14:29

I think this is really an important study. There was a

14:32

study that followed women with atypia for 14 years and they

14:35

found 66 Cancers and 331 women.

14:38

So the relative risk of developing breast cancer

14:41

in women with ADH in this study was about

14:44

four percent or fourfold increased

14:47

risk.

14:48

They found that if you had ADH diagnosed

14:51

when you were younger your wrist was higher and if you

14:54

had multiple Foci of ADH your risk was

14:57

higher as well. And this is I think published in

15:00

the New England Journal. I think a really important graph. So if

15:03

you look at the cumulative incidence of

15:06

breast cancer at a years out, this

15:09

is the blue line as women with one Foci

15:12

of dcis. The yellow or orange line

15:15

is with two Foci and the green is with three

15:18

or more Foci and you can see the more Foci you

15:21

have the more likely you are

15:24

to develop breast cancer, but I also think what's very interesting is

15:27

if we think about screening women at high

15:30

risk, and we use the American Cancer Society recommendations of

15:33

screening women at 20% are higher risk

15:36

that many of these women with the diagnosis of

15:39

ADH certainly with multiple ADH fill

15:42

that criteria fulfill that criteria and

15:45

in fact, should we be thinking about women with

15:48

PH differently particularly if it

15:51

was diagnosed young or if they have multiple Foci of ADH

15:54

in terms of Mr. High risk surveillance, and

15:57

certainly this data seems to support. Yes that by

16:00

10 years out women with three or

16:03

more Foci of ADH have reached that 20% risk

16:06

lifetime risk of developing breast cancer and

16:09

even women just with two Foci by about

16:12

12 years have reached that as well. So perhaps we

16:16

have to start thinking about ADH a little bit differently and

16:19

what the appropriate

16:21

Management is the nccn guidelines. The

16:24

guidelines of NCI designated Comprehensive Cancer

16:27

Network guidelines recommend surgical excision

16:30

of all ADH which is what we practice at our

16:33

institution, but there are a lot of women who go on

16:36

to surgery that have a diagnosis of

16:39

ADH and the hope is that with additional molecular

16:42

markers with mrnas that we can

16:45

find the Bad actors and and not

16:48

send in the future all ADH to

16:51

search the excision and perhaps dcis as well.

16:55

So

16:56

Screening guidelines for women with ADH, you

16:59

know, if we're thinking about the American Cancer

17:02

side of the ACR and nccn guidelines of 20%

17:05

lifetime risk, we don't really have sufficient evidence. But

17:08

we have some evidence to suggest that perhaps in

17:11

this high risk population annual screening Mr.

17:14

Or biennial screening Mr. May be very helpful, but

17:17

there are no prospective trials showing that and probably

17:20

this should be included in future trials.

17:24

Women with ADH often see medical oncologists to

17:27

look for or have discussions about chemo

17:30

preventions with the selective estrogen

17:33

receptor modulators often are offered tamoxifen

17:36

and that probably is

17:39

a very reasonable thing especially considering and

17:42

seeing what the risk of ADH is in this population.

17:47

Let's talk about papillary lesions papillary lesions

17:50

are ahead of heterogeneous group of lesions that

17:53

have a fibrovascular core surrounded

17:56

by epithelial proliferation. These are introductor lesions

17:59

found to constitute about one to

18:02

five percent of lesions found at cornedal biopsy

18:05

at percutaneous breast biopsy and

18:08

they can present clinically as Imaging or

18:11

palpable lesion or with nipple discharge and

18:14

his papillary lesions are in fact the most common cause

18:17

of bloody nipple discharge. Oh clinical precipitation.

18:21

This is what the pathology looks like on mammograms.

18:24

They can present a single or multiple

18:27

masses with or without calcifications. They can

18:30

in fact present with calcifications alone without an

18:33

Associated Mass. When you do an ultrasound

18:36

you often see introductal masses intriluminal masses

18:39

and an MRI, they're small enhancing

18:42

masses often with suspicious kinetics and

18:45

it's impossible based on Imaging to differentiate benign

18:48

from malignant papillary lesions. So here's

18:51

a woman a mammogram. You can see that she has multiple masses all

18:54

of these are papillary lesions and here on ultrasound

18:57

you can see these multiple influinal masses again

19:00

in a woman with papillary lesions.

19:04

And you can see a very bright papillary lesions which enhance

19:07

on kinetic fats

19:10

at fat saturated post contrast

19:13

images and they can be

19:16

bright on T2 as well.

19:19

The upgrade rate of benign papillary lesions of

19:22

varies as well, but you can see here it varies between 10 and

19:25

37 percent again variability in

19:28

the size of the populations included

19:32

in these studies, but I think what's really

19:35

important with papillary lesions to begin to look at different populations

19:38

in the

19:41

study the students to study from 2014. There

19:44

was no difference in the upgrade rate in her study, whether

19:47

core needle divisor vacuum assisted device was used the

19:50

second study here with the 21% upgrade

19:53

raid included both benign atypical and malignant

19:56

papillary lesion, and there was an article published

19:59

in 2014 that looked at just African-Americans with

20:02

a higher upgrade rate from papillary

20:05

lesions, but it's important to remember there

20:08

are different types of papillary lesions. There are benign

20:11

that is without atypia. There are papillary lesions

20:14

with atypia and frankly malignant papillary

20:17

lesions, which

20:19

Be both introductal and invasive papillary carcinoma.

20:22

And I think it's pretty clear that any papillary

20:25

lesion with atypion, of course malignant malignant

20:28

needs surgical excision. But the question

20:31

is, what do you do with benign papillary lesions, so

20:35

There's an international multicenter review

20:38

that showed an overall upgrade rate of 14% for benign

20:41

lesions benign papillary lesions, but

20:44

the upgrade rate for papillary lesions with atypia is

20:47

36% and there are now

20:50

an increasing number of studies particularly those

20:53

in which papillary lesions were biopsied with vacuum

20:56

assisted that showed no upgrade rate for

20:59

well sampled papillary lesions

21:02

without atypia and here's one comparing it

21:05

and showing a 10% upgrade

21:08

rate with atypia and a zero percent upgrade rate

21:11

without atypia. So papillary lesions without atypia

21:14

with no upgrade, right?

21:16

So what do we do?

21:18

Obviously any papillary lesion with

21:21

atypia or frankly malignant requires surgical excisions micro

21:24

papillary lesions with complete surgical excision,

21:27

we follow up with imaging we no longer

21:30

excise all benign papillary lesions particularly

21:33

those that were biopsied with vacuum assistance, and

21:36

we follow them with very strict radiologic pathological

21:39

correlation.

21:42

So here's a patient with extremely dense breasts with

21:45

the palpable Mass on ultrasound. She

21:48

had an interluminal heterogeneous lobulated

21:51

irregular Mass. She had

21:54

an MRI that showed a heterogeneous lobulated

21:57

enhancing mass and at

22:00

surgical at minimally invasive biopsy. It

22:03

was an atypical papillary lesion that at surgical

22:06

excision was in fact an invasive papillary carcinoma.

22:11

A radial scars the next high-risk lesion

22:14

that we are going to discuss.

22:17

A radial scar is the lesion that has a central

22:20

fibrolastic core with radiating ducts. And therefore

22:23

these radiating ducts is what causes that Starburst

22:26

or stellate appearance that is classically

22:29

associated with the radial scar. It's also

22:32

called the complex sclerosing lesion. If it's

22:35

greater than one centimeter, it can pathologically be

22:38

mistaken for a tubular carcinoma previously. We

22:41

used to discuss it being incidentally

22:44

found at biopsy of something else. But now

22:47

particularly with tomosynthesis, we can more clearly

22:50

and accurately see speculated lesion,

22:54

we can visualize the subtle architectural

22:57

distortions that are now associated with radial scars

23:00

and although there are no definitive studies yet. It

23:03

certainly seems that we will that we are seeing

23:06

more radial scars. It's been reported

23:09

to be a very small percentage of percutaneous breast

23:12

biopsies and here you can see

23:15

these ducts that are rad.

23:17

Getting out giving this a starburst or

23:20

stellate appearance and on a specimen

23:23

radiograph.

23:24

A correlate to what? We just saw pathologically and

23:27

on.

23:29

Imaging

23:31

it can be associated with calcifications. It can

23:34

be impossible to differentiate radial scars from malignant

23:37

lesions.

23:40

If you look at the upgrade rate of radial scars again,

23:43

they vary from a to to

23:46

22 percent and it

23:49

really depends on what you describe as an upgrade region upgrade

23:52

lesion the paper

23:55

by Miller West and patini showed

23:58

that it was a 22% upgrade rate for a higher risk

24:01

lesion. So that is and lobular neoplasia

24:04

or ADH but the upgrade rate

24:07

for surgery for cancer is somewhere between

24:10

point eight and eight percent again still

24:13

quite variable.

24:16

There's no evidence that radial scars actually will evolve

24:19

into malignancy, but rather that they are associated with

24:22

other higher risk

24:25

and malignant lesions in this proliferative lesion and

24:28

0 to 14% of radial scars are associated with

24:31

other high-risk lesions dcis or invasive

24:34

cancer and it can

24:37

so basically radial scars coexist with malignancy in

24:40

these as I said proliferative region

24:43

lesions and it's been

24:47

a malignancy tends to occur when

24:50

the radial scar is larger when the

24:53

patient is older and with the when there

24:56

is a mass and Architectural Distortion

24:59

versus what it presents as calcifications alone and

25:02

often the malignancy is found at the periphery at

25:05

pathologic evaluation.

25:09

Jessica Leong looked in at pure radial

25:12

scars with no other Associated proliferative disease

25:15

and the upgrade rate that she and her colleagues reported was

25:18

quite low at point six percent and another

25:21

study this in the same year by Donaldson again

25:24

found zero cancers,

25:27

81 were benign and 16 had high

25:30

risk lesions. So a low upgrade rate.

25:35

A study demonstrated that if

25:38

in fact there was an absence of Mr. Enhancement and

25:41

Radial scars that the that was an excellent

25:44

predictor of benignity and there was a zero

25:47

upgrade rate if there was no Mr. Associated suspicious

25:50

enhancement and very

25:53

similar in another study showed a

25:56

very very small upgrade rate to

25:59

malignancy when there's no Mr. Enhancement in the

26:02

region of the biopsy proven radial scar.

26:06

So what do we do we still surgically excise

26:09

all radial scar but I think increasingly we're looking

26:12

at it in a case-by-case and there

26:15

is support in the literature for

26:18

clinical and imaging follow-up particularly for

26:21

small lesions that on percutaneous biopsy

26:24

are found to be radial scars.

26:27

So

26:29

Lesions smaller than one centimeter you can if

26:32

they're biopsied with vacuum assistance sufficiently

26:35

sampled Imaging and

26:38

clinical follow-up is reasonable larger lesions

26:41

undergo biopsy with

26:44

vacuum assistance and Radial scars when targeting other

26:47

lesions incidental radial scars are certainly

26:50

safe to follow up with imaging and

26:53

clinical follow-up. Of course, if there's any other

26:56

atypia or Mr. Enhancement associated with

26:59

these biopsy proven radial scars, then the

27:02

decision is appropriate.

27:05

Let's talk it now about flat epithelial. Atypia.

27:09

Also called doctoral inter epithelial neoplasia

27:12

by the World Health Organization. It's considered a

27:15

borderline lesion. It may represent an early

27:18

stage in the development of certain low-grade malignancies. The

27:21

malignancies associated with flat epithelialitophia are

27:24

our low-grade malignancies.

27:27

It's characterized by a thin layer of epithelial cells

27:30

with cytologic atypia. And it's a

27:33

very rare lesion occurring in somewhere between one and

27:36

five percent of percutaneous breast biopsies. This

27:39

is what it looks like on pathology.

27:43

And when you when you do find neoplastic lesions

27:46

associated with FDA, they're usually

27:49

low grade dcis or invasive tubular

27:52

or lobular carcinomas with again a highly

27:55

variable rate of upgrade from 5 to 33

27:58

percent.

28:00

And the reason we find this variability is

28:03

because they're an infrequent lesion. Let's

28:06

see and therefore we don't have any definitive

28:09

studies. If you look at the published studies

28:12

of FEA the upgrade rate of

28:15

FDA, they ranges from 15% by

28:18

Perez a study showing 2.2

28:21

percent upgrade of FDA or FDA

28:24

with ADH of the 16% upgrade rate

28:27

and again a much higher upgrade rate with ADH associated

28:30

with FEA published

28:33

by on at all in 2016.

28:37

So data suggests that FEA is

28:40

not only a higher it if FEA is

28:43

the lesion alone that is found the highest risk

28:46

lesion that it's associated with an 11 to 14

28:49

percent risk of developing breast cancer in 10 years.

28:52

So very substantial. So the issue of

28:55

FDA is not only upgrade rate, but it's very important to

28:58

know a woman that has FDA has

29:01

a substantial tenure risk of developing breast cancer after the

29:04

diagnosis of FEA.

29:07

There really is no consensus on whether to surgically excise.

29:10

However, the data suggests that it's probably

29:13

the right thing to do. We need more multi-institutional studies

29:17

to help us understand what to do. What

29:20

optimal management of FDA is at our

29:23

institution all FEA goes on to surgical excision.

29:28

Now, let's talk about lobular neoplasia.

29:31

It includes a typical libular hyperplasia

29:34

and lobular carcinoma in situ. The

29:37

reason we call it lobular neoplasia is

29:40

because there's a very substantial variability in

29:44

what the pathologist will call the same slide Al

29:47

H or lcis and what

29:50

lobular neoplasia is is a monotonous disc

29:53

cohesive proliferation of small round cells with

29:56

low to intermediate nuclear grade that are evenly space

29:59

that both fill and distend the asini of

30:02

lobbles that are involved and this is what it looks like here.

30:05

You can see this distended filled labial with

30:08

these monotonous cells.

30:11

It's usually found incidentally for workup of suspicious lesions

30:14

and occurs in less than 2% of

30:17

percutaneous biopsies. And alh

30:20

is used to describe a lower grade lesion

30:23

that does not qualify for the diagnosis of lcis.

30:26

So less than 50% of the Asin

30:29

I are expanded or distorted by lobular cells and

30:32

all liabulations have a lack

30:35

of expression of ecadron.

30:38

Usually alh and lcis are multi-centric can

30:41

often be bilateral and they are

30:44

high risk lesions for subsequent development of

30:47

invasive breast cancer in either breast. So the

30:50

risk of developing breast cancer and women with the diagnosis of

30:53

alh has four to five fold with lcis. It's

30:56

8 to 10 fold. So there is definitely a

30:59

higher risk of developing breast cancer in women

31:02

with lcis as compared to alh.

31:06

And if you look at the upgrade rate of lobular neoplation

31:10

a number of studies again, look

31:13

at the small numbers of the cases included the largest

31:16

being 92 in these single single

31:19

institutional studies and you can see an upgrade

31:22

rate ranging from 2 to 25%

31:26

We published a multi-institutional study

31:29

some time ago. Now looking at over 32,000 image

31:32

guided needle biopsies from 14 institutions.

31:35

We found lcis or alh, so

31:38

lobular neoplasia and just under 1% of the

31:41

cases of which nearly 60% of them

31:44

went on to surgical excision so that we could see what the upgrade rate

31:47

was and we tried to stratify it by different

31:50

size by by Reds the biopsy device use

31:53

the guidance method used but you know, I do I do

31:56

want to point out that it is a study that was done fairly

31:59

early on in minimally invasive breast biopsy.

32:04

And we found that many of the variables that I just mentioned were not

32:07

significant, but we found that there was a 23% upgrade

32:10

rate at surgically at surgical.

32:13

It's just excision of lobular neoplasia. And this

32:16

is very similar to the upgrade rate that we find with ADH and

32:19

therefore we recommended surgical excision of

32:22

all not lobular neoplasia found at percutaneous

32:25

breast biopsy.

32:28

Um, and there are so again,

32:32

as I said, therefore we recommend that all patients

32:35

going to surgical excision and here's an example of

32:38

a 66 year old who underwent right invasive with

32:41

the history of bride invasive ductal carcinoma went to

32:44

bsgi to look for extent of

32:47

disease and here you can see her cancer in the right breast

32:50

and she had a focus of increased radio

32:53

Tracer uptake in the left breast. You can see it in the medial

32:56

breast on the CC. Medial Superior left breast

32:59

we went on to do a directed

33:02

Ultras fat ultrasound fine found this

33:05

hypocal lesion that I'm minimally invasive

33:08

biopsy was lcis at surgical excision.

33:11

She had an invasive lobular carcinoma.

33:15

That measured less than a centimeter a

33:18

half a centimeter unsurgical excision.

33:21

So there are other studies more recent studies

33:24

that have looked at lobular neoplasia surgical excision

33:27

a study of 285 patients that found

33:30

a 13% upgrade rated surgical excision and

33:33

their recommendations were also to send

33:36

all patients with Bob lobular neoplasia to

33:39

search the Excision.

33:41

However, not all agree, there is

33:44

a subtype of lobular carcinoma

33:47

inside two called pleomorphic. They can be pleomorphic for

33:50

two reasons. One is the Imaging can be

33:53

pleomorphic. They can have highly heterogeneous calcifications

33:56

or they can have

33:59

a more aggressive pathologic subtype under at

34:02

pathologic evaluation. And in fact,

34:05

there are some centers that only

34:08

excise pleomorphic globular carcinoma in

34:11

situ.

34:13

And in fact, the upgrade rate of pleomorphic lobular

34:16

carcinoma is much higher than traditional

34:19

lobular carcinoma.

34:22

So really again you hear this again

34:25

and again with Harvest lesions, there's no standard of care

34:28

not all institutions except for ADH where

34:31

there is a standard all the other

34:34

high-risk lesions really don't have we don't

34:37

really have a standard of care for

34:40

what to do with lobulonia pleasure and our institutions

34:43

all lobulonia place. It goes on to surgical excision

34:46

at some institutions only pleomorphic lobular

34:49

neoplasia or a lobular carcinoma in

34:52

situ goes on to surgical excision, but I

34:55

think what this points out as we really need well designed

34:58

strictly controlled multi-institutional

35:01

studies to help us understand how

35:04

to optimally manage lobular neoplasia

35:08

found at percutaneous breast biopsy.

35:12

And the last lesions illusion I'd like

35:15

to discuss is mucosylike lesions. These are lesions with

35:18

dilated spaces containing mucin or

35:21

associated with mucin and the surrounding parenchyma. They're

35:24

often found to be accompanied by

35:27

various pathologic finding ranging from

35:30

benign fibrocystic disease to atypical cells symbol

35:33

of frankly malignant mucinous carcinoma. It's

35:36

a very rare lesion.

35:39

And here you can see this pink mucin in

35:42

these dilated spaces that are associated with

35:45

mucus seal like lesions.

35:49

And again, very small series with

35:52

various upgrade rates. Look a

35:55

study looking at whether mucus seal like

35:58

lesions present is calcifications or masses both show

36:01

up to substantial upgrade rate with the higher association

36:04

with mucus seal, like lesions that present is

36:07

masses. But again the absence of

36:10

atypia in a mucus feel like lesion may allow for

36:13

radiologic pathologic correlation. And in this study

36:16

you could see that there was no upgrade rate

36:19

as compared to a 31% upgrade rate and you

36:22

can see a like lesions with atypia.

36:25

And here is a number of other studies looking at

36:28

the upgrade rate many of them have a zero

36:31

percent upgrade rate if there is no atypia. And

36:34

therefore there is certainly substantial literature

36:37

to suggest that mucosal-like lesions

36:40

diagnosed at minimally invasive biopsy or a

36:43

percutaneous biopsy with no atypia can

36:46

be watched with radiologic pathologic correlation.

36:50

Of course if there is a atypia associated

36:54

with the mucusal-like lesion than it

36:57

does require surgical excision as there is a substantial

37:00

upgrade rate.

37:02

so

37:05

we are beginning to increasingly only excise those

37:08

mucusially like lesions that have atypia and

37:11

I think again substantial literature to support

37:14

that approach particularly if the

37:17

lesion is well sampled.

37:19

so

37:21

we've been discussing these high-risk lesions for a long

37:24

time. And the reason is because we really don't have the answer except

37:27

for ADH. We really don't know what to

37:30

do with lobular neoplasia with mucusia-like lesions.

37:33

I think papillary lesions are becoming clearer that

37:36

the ones that don't have atypia can particularly the smaller ones

37:39

that are well sampled can probably be

37:43

Be followed. But the reason is that the

37:46

small series and also confounding lesions.

37:49

They are rare lesions often single institutional

37:52

studies and it is

37:55

also a very complex combination of

37:58

the modality in which

38:01

the lesion is identified the type of biopsy device

38:04

that's used in order to assess the

38:07

amount of sampling again larger vacuum

38:10

assisted biopsy device are associated with

38:13

a lower upgrade

38:16

rate. So and then

38:19

the other question is if there is an upgrade rate of 2%

38:22

or higher do we have to surgically excise it?

38:25

Can we extrapolate from a byrad's

38:28

three lesion and can we watch lesions that

38:31

have a 2% or less likelihood of

38:35

malignancy? And the answer is we really don't know and

38:38

we really need a multi-institutional definitive

38:41

studies to help us understand this so

38:44

really the issue with a high

38:48

risk lesions is you don't want to over

38:51

treat but you also don't want to miss the opportunity

38:54

to not to diagnose an early

38:57

curable breast cancer. We want to save patients

39:00

from unnecessary surgery but what unnecessary

39:03

surgery is does that mean any lesion

39:06

that has a 2% or higher likelihood of

39:09

malignancy? Should they go to surgical excision?

39:13

Um to exclude the the adjacent malignancy and

39:16

the answer as we really don't know but what

39:19

we do now, we do know and how we approach it

39:22

at our institution. I think

39:25

ADH gratefully is very clear ADH needs

39:28

to go on to surgical excision. And that is the standard

39:31

of care papillary lesions. Radial Scar

39:34

and mucus feel like lesions with no a tipia particularly

39:37

those that are small and well sampled

39:40

with vacuum assisted biopsies can likely be

39:43

followed with very close radiologic pathologic correlation

39:46

flat epithelial. Atypia. We are

39:49

exciting all of them. I think that's probably the

39:52

prudent thing to do again, no concessed consensus

39:55

and lobulinia pleasure. We

39:58

exercise them all but it's certainly supportive in

40:02

the literature. Just just excise. There are

40:05

some studies in the literature to support just exercising plea

40:08

morphic lobular. Carcinoma Insight too. So

40:11

in conclusion

40:13

high-risk lesions are indicative of both

40:16

an increased risk of breast cancer with different

40:19

risks for different lesions, but when found on percutaneous

40:22

breast biopsy many require surgical excision,

40:25

but I think what we are understanding better

40:28

is which lesions require surgical

40:31

excision and which don't and certainly

40:34

there are a group of lesions that

40:38

That we still are not sure what to do with and exactly

40:41

how to screen women that

40:44

have these high-risk collegians whether Mr. Is

40:47

The Prudent way to go consider them

40:50

in the population of 20% higher or higher

40:54

lifetime risk of developing breast cancer. And again

40:57

what the role of chemo prevention is in this population of

41:00

women. So with that I

41:03

thank you and I will

41:06

see let's see if

41:09

I can.

41:11

See if there are questions in the chat box questions and

41:14

answers.

41:18

So the question the first question is what

41:21

by ads do you give for papillary lesion without atypia?

41:24

Well, we followed them carefully with

41:27

imaging and so we would give

41:30

that a bi rats three as we do for every biopsy

41:33

except for fibratenomas insists that

41:36

resolve for six months follow-up and then we can continue

41:39

with bi rats three with annual follow-up.

41:43

Um, how do you follow radial scars after

41:46

excision again? Similarly? Give it a buy rats

41:49

three.

41:51

Follow it at six months and then continue with the

41:54

buy rats three for annual follow-up. What are

41:58

the time intervals of and period of

42:01

follow-up of the nine radial scar? I think we just talked

42:04

that is their recommendations for lcis to

42:07

go to surgical excision. The answer

42:10

is yes, I think lcis is very reasonable.

42:13

We certainly send all of our lcises. We

42:16

sent all of our alh just to search

42:19

Google excision. But as I mentioned there is no consensus to

42:22

that and

42:27

And I think we need more data to better understand which of

42:30

these lesions how do we go forward and stratify

42:33

these lesions to understand which ones need

42:36

Surgical excisions and which ones don't

42:39

but at our Institution.

42:44

At our institution. We sent all lobular near pleasure

42:47

currently to surgical excision.

42:51

What is the standard biopsy needle gauge and all and all

42:55

your percutaneous biopsies done vacuum assistance?

42:58

So no, we do our ultrasound guided

43:01

biopsy with a spring-loaded 14 gauge device. There

43:04

are many practices that do use a vacuum assisted

43:07

device and there is certainly Merit to

43:11

that you certainly get more tissue than that and we

43:14

use a 14-gauge. So

43:17

we use a nine gauge vacuum assisted biopsy

43:20

device for tactic biopsy.

43:25

So Dr. Storella asks, how do you

43:28

manage papillomatosis and recurrent enhancing masses

43:31

on MRI? So that is really a hard

43:34

one. But I think following them

43:37

with MRIs is a very reasonable way

43:40

to go. If if one of these, you know,

43:43

a couple of mitosis in women is really a confounding

43:46

situation and I think Mr. Is

43:49

really perhaps the best way to

43:52

follow these women because you can

43:55

follow these multiple masses if one um,

43:58

suddenly grows rapidly or

44:01

significantly changes, it's kinetic pattern

44:04

then you know, which one to Target otherwise, you

44:07

know, these women with capital mitosis. They

44:10

just have these two numerous to to count

44:13

masses and what are

44:16

you going to do with them? So we rely heavily on Mr.

44:19

To look for Rapid interval growth or substantial

44:22

kinetic change to help us decide if

44:25

any of these two numerous to count lesions

44:28

masses require biopsy.

44:33

If you suspect a diagnosis of

44:36

radial scar.

44:39

Why not go straight to surgical excision. So for

44:42

a number of reasons, we don't

44:46

go to surgical excision for any lesion. First of all, there

44:49

are some radial scars that are fat necrosis,

44:52

right certainly fat necrosis can look stellate. And

44:56

so if it's a totally benign lesion, we

44:59

certainly don't send the patient to surgery

45:02

it in fact,

45:05

so I you know, I think it is a

45:08

better for the patients the less aggressive surgery

45:11

to have a preoperative diagnosis of

45:14

knowing what you're going for. If something is perhaps this

45:17

area of architectural is

45:20

in fact cancer, and so cancer surgery is very

45:23

different than a diagnostic surgery. And

45:26

I think there have

45:29

been numerous studies that have shown that a pre-operative

45:32

diagnosis results negative

45:35

margins at a much higher rate. So the

45:38

reason you want to know what something is prior

45:41

to going on to surgical decision is

45:44

because in fact, it may be completely been

45:47

on and not require any surgery or May. In

45:50

fact be cancer and require more aggressive initial surgery

45:53

to achieve negative margins. So that's

45:56

why it is best for these patients to

45:59

have a biopsy and

46:02

a diagnosis.

46:02

prior to surgery

46:05

For surgical excision of breast for lcis lobular

46:08

carcinoma de laros breast.

46:11

I'm not the question is for surgical excision of

46:14

breast.

46:15

For lcis lobular carcinoma bilateral or

46:18

unilateral breasts. So, you know

46:21

for lcis you would do surgical excision of the lcis

46:24

lesion that you diagnosed, you know

46:28

at our institution. We actually do Mr. And

46:31

every newly diagnosed Mr. Bsgi in every newly

46:34

diagnosed breast cancer that in of itself is controversial. However,

46:37

most institutions will do an

46:40

MR on a patient with lobular carcinoma

46:43

to see if in fact there are it's more

46:46

you know, there are multiple lesions if there is a bilateral lesion prior

46:49

to definitive surgery. So I I

46:52

think that is the question certainly, you know,

46:55

if someone has lcis you do a preoperative

46:58

localization and surgically excise that lesion

47:01

to see if that lesion is

47:05

has adjacent malignancy, but that's

47:08

a very different question than how do you treat or

47:11

how do you follow women with a lobular carcinoma

47:14

inside to in terms of surgery?

47:19

Um, as you said radial scar associated with malignancies, that

47:22

means we have to remove the completely rather than follow

47:25

up. Yes, if a radial

47:28

scar is associated with malignancy. It has to be treated as a

47:31

Cancer and as we all know the treatment is,

47:34

you know lumpectomy and radiation

47:37

mastectomy. It really depends on the follow-up and

47:40

that particular patient.

47:43

How do you integrate risk factors modeling

47:46

with the lesion requiring follow-up to

47:49

consider other screening protocols such as mammogram with

47:52

Mr. It's at six months intervals. So, you know,

47:55

I think that's a really big question.

47:58

Um, yeah, we don't have the perfect risk model.

48:01

We many of the risk models don't incorporate

48:04

high risk Legions and therefore

48:07

we don't know what to do with them. But I think

48:10

what really is important is that New England

48:13

Journal paper article that was a fairly long

48:16

follow-up of the substantial number

48:19

of women that showed that the presence of

48:22

atypia results of

48:25

ADH was particularly as I said in younger women

48:28

and in multi-foot focal ADH results

48:31

in a very substantial risk of breast cancer,

48:34

well above the 20% lifetime risk

48:37

that we associate with the need for Mr.

48:40

Surveillance, and we don't normally use Mr. Surveillance

48:43

with women with ADH and therefore, I think

48:46

it's really important to think about that. Should we reconsider?

48:51

How we surveil how we

48:54

follow women young women with ADH or

48:57

women with multifocal ADH and I'd like

49:00

to say yes. I think it would be prudent and

49:04

in the patient's best interest, but of

49:07

course we have to balance the false

49:10

positives the costs and other

49:13

issues, but I think the data is becoming increasingly compelling

49:16

that the presence of ADH is

49:19

associated with the very substantial increase

49:22

risk of developing breast cancer that may well

49:25

hit the 20%

49:28

lifetime risk that will recommend result

49:32

in the recommendation of annual screening MRI, so

49:37

but I think it also shows that there is no perfect risk factor

49:40

model and we need to get more

49:43

sophisticated ones associated with radiomics and

49:46

and other factors and I think as we

49:49

move towards AI

49:53

Risk assessment we might get better integrating.

49:56

The information that is

49:59

in a woman's mammogram associated with high

50:02

risk lesions found a biopsy as well.

50:06

What is the role of contrast enhanced mammography in the

50:09

follow-up of high-risk lesion can it replace Mr. I don't

50:12

know the answer to that. I don't think we have the answer

50:15

to that yet, but it's a very intriguing question. It certainly

50:18

would be a a cost-effective way.

50:21

But you know, it's very likely that

50:25

these high risk lesions will enhance with contrast

50:29

enhance mammography just like many of them do

50:32

with Mr. And in

50:35

fact perhaps that's one of the things we can use to triage these

50:38

lesions that you heard that radial scars

50:41

that don't enhance an MR May in fact

50:44

be watchable if that's a word and

50:47

perhaps that is translatable to

50:50

contrast enhance mammography, but I don't believe

50:53

that data is out there.

50:55

What percentage of breast cancers are non-enhancing on

50:58

Mr. That's an interesting question. I

51:01

think I'm aware of a couple of studies one from

51:04

the Japanese literature that supports or that

51:07

has reported rates as high as seven

51:10

percent of breast cancer. So, you know morphology first

51:13

always morphology first and then

51:16

kinetics so

51:19

Um, I hope that answers that question.

51:23

For the buy rats three lesions post biopsy. Do

51:26

you follow with diagnostic mammography at just six months and 12

51:29

months post-biopsy then revert to screening or do

51:32

you follow with diagnostic for two years? We will follow with

51:35

diagnostic for two years, but at

51:38

12 month intervals after the initial six month.

51:44

So breast MRI demanded steadily increasing some

51:47

associations consider patients with the

51:50

history of treated breast cancer as a moderate risk, you have to

51:53

undergo Mr. Screening. What are your thoughts?

51:56

um

51:57

So I don't think we have standards for that.

52:00

I think there is substantial fairly

52:03

robust data in

52:06

the literature that suggests that women with the personal history of

52:09

breast cancer are at moderate or

52:12

high risk, and we certainly know

52:15

that doing screening Mr. And women with the personal history

52:18

of breast cancer finds many more cancers than

52:22

with traditional screening with

52:25

mammography and ultrasound alone. So my thoughts

52:30

are that more data is

52:33

needed but women with the personal history of

52:36

breast cancer definitely benefit from Mr. In

52:39

terms of fun. They are much higher risk and therefore

52:42

a fine finding earlier more curable

52:45

breast cancer. So

52:48

Um, I think that is the last question. Let's

52:51

see there are and if

52:55

there are any other questions, I would

52:58

be

52:59

happy to answer them.

53:04

And if not, I I thank you all for

53:07

being here. It's it's a pleasure and

53:10

I thank you all for the work that you're doing to

53:13

to help

53:17

find early curable breast cancer.

53:20

Dr. Brown, thank you so much for your lecture today and thanks

53:23

to all for your participation in our new conference a reminder

53:26

that you can access the recording of today's conference and

53:29

all our other previous new conferences by creating a free MRI online

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account. MRI online has launched a

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new breast Imaging focused membership plan to help

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you gain confidence with breast MRI memos Tomos and

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ultrasounds. Learn more at MRI online.com/press.

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Be sure to join us next week on Thursday, November 3rd

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at 12pm Eastern time for a lecture with Dr.

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Jeremy height on the acute ischemic stroke

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Imaging you can register for this lecture at mriline.com

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and follow us on social media for updates and

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reminders on upcoming and conferences. Thanks again and

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have a great day.