(anticipatory music) - So when women have an annual mammogram, there is now a density score, either A, B, C, or D, with D being the most dense and A being the less dense.

And the problem with routine mammography is when there is dense breast tissue, it's very difficult to see small lesions.

So if a woman's mammogram does come back with high breast density, it's really important to talk with their physician about secondary screening.

And that could come in the form of an ultrasound or a breast MRI, depending on their individual risk.

- Most women do not know their level of risk.

This results in most patients not receiving the appropriate imaging tests to screen for breast cancer.

(gentle music) - Carrie was taken from me at age 52.

(gentle music continues) She had a routine mammogram.

That was back in 2016.

That was in June of 2016.

And that mammogram showed that there was a suspicious mass, and therein lies the problem.

So for the next two years, she would have her mammogram.

She would get a report.

Like every woman, she's on pins and needles to get that report.

And then when you get the report back, it'll say, "No suspicious findings."

And then underneath that, it'll say, "Heterogeneously dense breast tissue."

And it might have another little line after that that says, "Small masses are not detectable in some cases with mammography alone."

But no one knows what that means.

And most women don't even know what that means today.

(suspenseful music) - [Announcer] Major funding for this program was provided by: - [Announcer] The Promise Fund's mission is to increase survivorship from breast and cervical cancer by providing guided support and access to screenings at no cost to you.

That's our promise.

Learn more by visiting ThePromiseFund.org.

- [Announcer] ABCD: After Breast Cancer Diagnosis provides free virtual, personalized emotional support to anyone impacted by breast cancer, anywhere, at any stage, from someone who gets it and gets you.

- [Announcer] National Breast Cancer Foundation helps women by providing help and inspiring hope to those affected by breast cancer, through early detection, education, and support services.

To find out more, visit nbcf.org.

(gentle piano music) - So time goes on.

(gentle piano music continues) Two years down the road or so, after a couple more routine mammograms only, only mammograms, she felt a lump in her left breast.

So, consequently, it stands to reason that those tumors grew behind that dense tissue and these were both found to be malignant.

And at the time, she was categorized or staged at Stage 3C.

She had extreme lymph node involvement at that time.

- It's important to know your breast density because breast density is one of many risk factors to develop breast cancer.

Breast density is the amount of breast tissue relative to fat within the breast itself.

So breast density does two things.

Number one, it increases a patient's level of risk for developing cancer.

And number two, it makes it harder for the doctor, like me, who looks at the mammogram, to find the cancer separate from that breast tissue.

It can obscure or mask the underlying cancer.

Most patients do not understand their level of risk.

So the first step is to have a conversation with your healthcare provider about your risk factors for cancer.

(bright acoustic music) - The easiest description of Carrie, first and foremost, she was a tomboy.

She loved to fish.

She loved the outdoors.

She would outshoot most men, and I'm not kidding you.

She might wade waist-deep in a creek, fishing, and then that night, she'd put on a dress and high heels, and we'd go to dinner.

This is her John Deere tractor.

She's had this thing for 20 some years.

And this was kind of her release.

This is where she'd go out and put her earbuds on and ride around and mow, and she'd stay out.

She'd stay out from sun up to sun down on this thing.

(gentle somber music) Carrie has Scottish Highlander cattle.

They're the long-haired cow.

They're pretty cool.

And I think we've got about 20, 22 head of them right now.

And she's had, you know, some of these, when they were just little bitty calves.

They would become almost pets, like dogs to her.

I mean, they'd walk around.

You can hand-feed these, actually.

They're pets.

Yeah, we don't sell these.

If we need beef, we go to the butcher shop.

(chuckles) Yeah.

(tractor rumbling) She's also got bison.

She had 30 head of bison.

We've got about 40 head of elk here on the farm.

(bird chirping) But she was also a very savvy businesswoman.

She was the head of multiple businesses in Indianapolis and Kentucky and a few other states.

You know, you hear a lot of people talk about, "This is one of the nicest people, nicest, friendliest person I've ever seen."

That was her.

She'd walk in a room, make friends with anybody.

She'd cook for an army.

We don't have many neighbors out here, but the ones that do learned to come over on the weekends and eat 'cause we always had so much food.

Towards the end, once she was diagnosed with cancer and then fought the first round of it, and then she ended up getting the metastatic brain tumor, they told us at the time that it was actually collapsing, what's called the cerebral aqueduct.

So they had her surgery.

The next step was radiation because they wanted to radiate the tumor bed.

And we saw, about two years after surgery, she started having a little cognitive decline.

She couldn't do the thing she used to do.

We were vacationing, and she slipped and fell on the hardwood floor.

And she said, "Well, I tripped over the dog toy."

And I said, "Well, okay, she generally doesn't do that."

So two or three days later, she said, "You know, I'm starting to have double vision for some reason."

And I said, "Well, okay, maybe we need to go see the doctor about that."

And she said, "I'll tell you another thing.

This is kind of strange.

I write with my right hand, and I'm having difficulty writing right now."

Called her family doctor, and he said, "Well, you need to go in.

We gotta get you an MRI."

So we took her in, we got her MRI, and the worst thing you can imagine, the results came back that she had a brain tumor, a metastasis in the right side of her cerebellum.

It also looked like she had a few small lesions on her left side of her cerebellum.

- Here you've got the upper portion of the brain, and then you have the lower portion here and the cerebellum.

And this is that tentorial space that separates the upper portion of the brain from the lower portion of the brain.

And you can see here from the side view where these metastasis are located.

And the infratentorial space is more responsible for where we are in space, such as our balance and our capacity to go up and down stairs and know where we are on that stairwell.

So if patients present with disease in the infratentorial space of the cerebellum, they may be very unsteady on their feet or have frequent falls.

- And the next day, she looked at me, and one eye went completely over to one side and the other eye stayed straight, and then she started to seize.

So we called 9-1-1.

(siren wailing) And 9-1-1 came, got her in the ambulance, and they took her in.

(monitors beeping) She was in the ICU for about four or five days.

They had her on a feeding tube.

Things were looking great.

The doctor came in and said, "We've got this.

Everything's working right, and we're gonna transfer her to the rehab floor."

And we said, "That's awesome."

And we did transfer her to the rehab floor.

And that first morning, she was able to get up on her walker, and they were impressed.

She was able to get up for PT, and she was able to walk about 20 feet and come back.

They were extremely impressed.

And the next morning, I went and got a coffee, and I came back in to wake her up, and she was nonresponsive.

And I tried to shake her, and she still didn't respond.

I called the nurses in, and they came and looked at her, and they thought, "Well, her vitals all look good," you know, and everything, and maybe she's just having a reaction from whatever drug they would've given her the night before for sleeping.

They'd given her some sleeping pills.

They ultimately took her away to get a CT, and she had had a brain bleed in the night, and it was too far gone.

(gentle somber music) So I had to make that call.

(gentle music fades) - Metastatic disease to the brain remains a challenge in the treatment of metastatic breast cancer as a whole.

The blood-brain barrier makes it very challenging for the medications that we give to penetrate the brain in adequate and appropriate concentrations.

The good news is that we're making significant amount of progress in the medications that can cross the blood-brain barrier, but we still have a lot of work to do.

- It's important to be able to detect these brain metastases early when they're small in size and small in number because being able to treat them early means better control with less toxicity of treatment.

Dr.

Anders is a medical oncologist here that specializes in breast cancer, and more specifically, specializes in brain metastases from breast cancer.

- It is interesting, the BRCA2 component.

You know, we do see breast, prostate, pancreas cancer, and we do have the talazoparib and olaparib compound.

- She brought with her a tremendous expertise in not only breast cancer, but also in solid cancers at all that had metastasized to the brain.

This was really something that she was passionate about, and it's become a tremendous need within the cancer arena.

As we actually get better at treating patients with cancer, they actually survive longer to develop things that are typically late stages of cancer, like brain metastasis.

So when she arrived, we knew that she'd bring a clinical focus on that, as well as a research focus.

And we got to work pretty quickly, she and I and, the whole team, frankly, in building research infrastructure around that.

And she's been a force of nature in getting that assembled here for us.

- [Dr.

Kirkpatrick] I think Dr.

Anders is a breakthrough woman in science because she's taking a multidisciplinary approach to the treatment of brain metastases.

- She is at the forefront, at the leading edge, and she is a paradigm-shifter.

But I think a lot of us say, "Who do the experts turn to?"

right?

And that's how you know that you're that person that has forged a path.

And I would say, I've learned over the years that Carey is the expert that the experts turn to.

- I grew up in a medical family.

My grandfather and five of his brothers were all physicians.

They actually all went to Duke and started a clinic in our hometown.

So really, from the time I can remember, medicine was just a huge part of our lives.

It was actually my paternal grandmother who really opened my eyes to medicine.

She was whipper-snapper smart and wanted to be a physician, and grew up in Alabama and was told that women aren't doctors.

So she instilled in me at a pretty early age, middle-school age, that I should pursue the career of my choosing, medicine or not.

And I ended up majoring in psychology at Vanderbilt and minored in French, which is not the typical path for most physicians.

But as I was going through my psychology degree, I was in my neuroscience class and was just really intrigued by the physiology of the brain, the structure of the brain.

- [Jamie] Come in.

- [Dr.

Anders] Hi.

- Hi.

- How are you today?

- Good.

- Good to see you.

- I had a fall, and two weeks after that, had another fall.

So I fell twice within two weeks, and it was very unusual.

And so I went to my primary care physician, (gentle music) and they discovered that I had a tumor in my brain, and the pathology came back that my breast cancer had metastasized.

- You can see an immediate beautiful response to the surgery where they resected the mass.

- It was after the surgery that I met with Dr.

Anders for the first time.

She immediately was just a comfort from the moment I walked in, like a breath of fresh air.

Meeting her and her bedside manner was just wonderful.

I was really excited to meet her and get to work with her as a specialist for brain and spine metastasis.

So I was lucky to be in her hands.

- All right, so we'll start with eyes.

- If you look at the treatment of brain metastases, 20 years ago it was primarily radiation oncology for treatment with either whole brain and some radiosurgery, and then surgery for treatment resection.

We really didn't have some good tools when people had multiple brain metastases or widespread disease.

- We've come over the past 20 from basically excluding patients with brain metastasis and some spine, some forms of spine metastasis from any promising novel therapy through a clinical trial, to actually designing clinical trials for that patient populations.

Part of that was what was happening in the field in the 2005 to 2008 timeframe.

We had just seen the advent of this really promising, exciting new drug called trastuzumab, which was effectively an antibody against HER2.

And we see that patients with HER2-positive breast cancer have higher incidence of brain metastasis in the metastatic setting, up to 30%.

One in three women will have brain metastasis.

So these antibodies were doing a beautiful job for extracranial disease control.

The lung metastasis were decreasing, the liver metastasis were decreasing, but we were seeing this escape to what we call the sanctuary side of the brain, and we had nothing.

So that was really where I decided to pursue systemic therapies in concert with radiation and surgery to help control disease in the brain.

- I think early intervention for breast cancer before it spreads is, of course, the best you can hope for, because once it's spread, there's a lot of other treatments that you have to start thinking about.

And some of those have failure rates associated with them, of course, but if you catch metastases to the brain, for instance, early, typically they're going to be smaller.

And if you're catching them before they're symptomatic, that's usually the case as well.

Anytime something's smaller, a lot of things tend to work better, you know, sort of logically.

Radiation works better, sometimes systemic therapies work better.

You probably don't need a neurosurgeon because neurosurgeons are generally involved when the lesions are larger and symptomatic, to the point where radiation might not work without us getting them out first.

So as these things get larger, they start to cause symptoms, they start to cause problems, they start to make it so that therapies don't work as well.

- The idea of surveillance MRIs in the setting of advanced breast cancer is a pretty controversial space.

I was honored to be part of the ASCO guidelines for HER2-positive breast cancer brain metastasis.

And we effectively said we cannot recommend for or against brain MRI surveillance in the advanced setting, largely because there wasn't a lot of data.

So now we are starting to see some emerging data that, if we select patients who are higher risk in the advanced setting and do surveillance brain MRIs at the onset, we will probably pick up about 10 to 15% of occult brain metastasis, asymptomatic, the patient didn't know they were there.

If we go out six more months, it could be upwards of 25%.

And this is work that's ongoing at the Moffitt Cancer Institute.

(bright upbeat music) - NCCN screening has recommended that, you know, brain MRIs really only be recommended in women when suspicious CNS symptoms are present.

So that means that oncologists really aren't ordering brain MRIs until, you know, patients exhibit symptoms like headaches, seizures, issues with balance, coordination.

And that can also mean that we're then detecting, you know, brain metastasis from breast cancer at a later stage than we are from other cancers where brain MRIs are routinely conducted per the NCCN guidelines, like lung cancer and melanoma.

Hi, Janice.

How are you doing today?

- Good, thank you.

- I think by introducing Brain MRIs into surveillance at, you know, an earlier stage in the breast cancer journey, I think that we stand to potentially improve meaningful clinical endpoints, like overall survival and progression-free survival.

We can see that it's stable.

There isn't really any major change there.

That's good.

We were just seeking to answer a simple question.

You know, in our Stage IV breast cancer population, what is the rate of asymptomatic brain metastasis?

And so we enrolled the three major subtypes of breast cancer.

So triple negative, HER2-positive, and HR-positive, HER2-negative, or hormone receptor-positive, HER2-negative breast cancer.

And our plan was to enroll 30 patients with triple negative breast cancer, 30 HER2-positive breast cancer patients, and then 40 hormone receptor-positive HER2-negative breast cancer patients that had progressed past first-line therapy.

Our plan was to just do a baseline brain MRI in those patients, and then, if negative, we would do another brain MRI six months later.

And really, our goal was just to see what the rate was of asymptomatic brain metastasis in these patients.

So we found that, at the point of the initial baseline MRI, the highest rate was in triple negative patients.

About 18% of those patients had brain metastasis, followed by HER2-positive breast cancer.

15% of patients enrolled had brain metastasis, and then 10% in the hormone receptor-positive HER2-negative group that had progressed past first-line therapy.

We conducted then a second MRI at six months, if the baseline brain MRI was negative in those patients.

And then, by that point, essentially a quarter of all patients, regardless of their subtype, had brain metastasis.

I think we were surprised that, you know, the rate was that high in our patients.

You know, there really wasn't much data to kind of guide us in terms of the rate of asymptomatic central nervous system metastasis in these patients.

You know, I think we were suspecting that maybe the rate would be closer to maybe 10, 15%, but to kind of see that rate of a quarter of patients, regardless of their subtype having brain metastasis, that was quite dramatic.

So one in four patients, you know, by six months, developed central nervous system metastasis in our study.

- The current clinical guidelines do not recommend routine surveillance or screening for patients who are asymptomatic.

I think that those guidelines will eventually change because I think that there are certain patient populations that probably would benefit from routine surveillance for brain metastases, for example, those patients with HER2-positive breast cancer, because we know that HER2-positive disease has a propensity to spread to the brain.

But, unfortunately, right now our clinical guidelines in asymptomatic patients do not recommend routine surveillance for brain metastases.

- Do you want to do it like the reradiation patients?

- Yeah, reradiation.

- Okay.

So I do think that there needs to be more work done.

We conducted our study solely at Moffitt, but it'll be important to verify these results in larger-scale trials that are prospective, conducted at a number of cancer centers and institutions, to verify these findings and to make sure that we're being clear in terms of our recommendations for brain MRI surveillance in breast cancer.

- When I think back to my fellowship, a diagnosis of brain metastasis usually conferred a life expectancy of upwards of six, maybe 12 months.

And I'm happy to say, in my practice now, I have patients well beyond the five-year, some even in the 10-year space.

So I think we're seeing significant improvements in the outcome of patients, which allows many of our industry partners to be more compelled to allow patients with brain metastasis in clinical trials.

(bright piano music) (gentle music) - We're setting up a foundation in honor of Carrie, and it's gonna be called CarrieLynCares.

And, basically, it is to build awareness on the breast screening, and it's to build awareness on the pre-screening of the brain.

(engine rumbling) Here we're gonna have a lodge.

We envision bringing folks out here, they can get a little bit of a getaway.

They can, you know, talk about the elephant in the room and have a place to relax.

So that's really what we want to do.

(water rushing) (insects chittering) This was her favorite location.

Once she saw this spot, she said, "This is the place."

And she said, "This is the place for the future foundation."

There's a spot down there that she would sit at that lake, as recent as last fall.

She'd love to sit there and just, she'd sit there for two or three hours at a time, just looking down that lake, and she could see the vision of other people doing the same.

(gentle music) Carrie would still be with us today if she would've had the proper supplemental screening, and she wouldn't have been debilitated, and she wouldn't had to go through the things she did in the last 2 1/2 years on her life after getting the brain tumor if she'd have been given the proper advice and knew what to look for.

The goal is to prevent what happened to Carrie from happening to other women.

(warm gentle music) (warm music fades) - I think that STEM really gives women the opportunity to shape the future.

I think that women really bring a very unique voice and perspective to the table, and it really allows us to create stronger, more impactful solutions.

- I think it's critically important for women to pursue careers in STEM, being able to take that scientific curiosity, whether or not it's around medicine, whether or not it's around engineering, whether or not it's around the basic biologic, chemical, physical sciences.

So I think it's something that we should absolutely continue to support, so that women will continue to pursue careers in STEM.

Oh, thank you.

- Thank you.

- [Announcer] Major funding for this program was provided by: - [Announcer] The Promise Fund's mission is to increase survivorship from breast and cervical cancer by providing guided support and access to screenings at no cost to you.

That's our promise.

Learn more by visiting ThePromiseFund.org.

- [Announcer] ABCD: After Breast Cancer Diagnosis provides free virtual, personalized emotional support to anyone impacted by breast cancer, anywhere, at any stage, from someone who gets it and gets you.

- [Announcer] National Breast Cancer Foundation helps women by providing help and inspiring hope to those affected by breast cancer, through early detection, education, and support services.

To find out more, visit nbcf.org.

(bright music) (bright music continues) (bright music continues)