Managing the Differences between Invasive Lobular Breast Cancer (ILC) and Invasive Ductal Breast Cancer (IDC)

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase 1 and sarcoma programs. Today I'm happy to be joined by Dr. Megan Kruse, a breast medical oncologist at the Taussig Cancer Institute. Dr. Kruse has previously joined this podcast to discuss advances in lobular breast cancer research. She's here today to discuss differences in the clinical management of invasive lobular breast cancer and invasive ductal breast cancer. Welcome back, Megan.

Megan Kruse, MD: Thanks for having me. Happy to be here.

Dale Shepard, MD, PhD: Maybe you could start off and remind us what you do here at the Cleveland Clinic.

Megan Kruse, MD: I'm a breast medical oncologist here and I have a footprint in clinical care of patients, but also in clinical research. And one of the big areas that I'm interested in right now is lobular breast cancer, so leading into this conversation and this study, and hoping to develop some clinical trial work in this space.

Dale Shepard, MD, PhD: So there's a wide range of people that might be listening in. Lobular breast cancer, tell us a little bit about how that differs from when someone says breast cancer, what does lobular breast cancer mean? How frequently does it occur? Tell us a little bit about the background here.

Megan Kruse, MD: I'm glad you asked that because most people when they hear breast cancer, they think of just one disease. And really we have multiple different groups within there. And lobular is one that doesn't always get a lot of attention, largely because over 95 percent of lobular breast cancers are hormone-driven. And so when we think about the diagnostic steps and the treatment steps, all of it is really geared towards the fact that these cancers grow off of hormones. And so for the longest time we said that was good enough. We have treatment for these cancers. We don't really have to think differently about lobular versus ductal cancer. And really that is a distinguishing feature. When the pathologist looks at the cancer biopsy under the microscope, they can tell based on the organization of the cancer cells, is this lobular, is this ductal?

And so lobular cancer is about 15 percent of all the breast cancers that we see. As I mentioned before, it is almost universally hormone receptor positive or grows in response to estrogen and progesterone, and it usually is HER2 negative. And so that is kind of the setup for how we think about treating these patients. But once you start treating them, you realize that they have a little bit different pattern in terms of how they present and what their recurrences look like. And that's what caught my interest.

Dale Shepard, MD, PhD: And so let's start off at the very beginning. That would be the diagnosis part and the presentation part. How are lobular breast cancers different?

Megan Kruse, MD: They're actually hard to diagnose in many ways just based on imaging. And that is because when these cancers form, they grow in these little single file lines. So I always think of them as sort of ants marching through the breast. And what happens with that is that you don't have the formation of a solid mass, at least initially. So these are cancers that may not show themselves as pea-sized lumps or marbles in the breast that a patient would find. More commonly they present as a vague thickening of the skin, sometimes a heaviness of the breast or one breast feeling a little bit different size or different fit in a bra.

And these are things that month-to-month women can experience normally so it's hard to pin it down at an early stage. Once it progresses, you often will develop a regular mass, like you expect, or lymph nodes that are swollen under the arm. But initially the changes can be quite subtle. And even if a patient notices those subtle changes or a doctor picks up on that on an exam, when a patient goes to have a mammogram, these cancers can be hard to see because those single file cell lines, even as they grow and get a little bit bigger, they can hide within the normal breast tissue. And so for women, especially women with dense breasts, their mammograms can look completely normal even if a lobular cancer is hiding there.

Dale Shepard, MD, PhD: So let's go to the other end. And you talked about recurrence and how recurrence is different. Give us a little insight on that.

Megan Kruse, MD: And this was the thing that actually got my interest in lobular cancer going, is that these patients just have this particular pattern of recurrence where the recurrences tend to happen late. And so if you look at five-year breast cancer survival numbers or even 10-year breast cancer survival numbers, they may not look all that different compared to ductal cancer counterparts.

But once you start to look after that, 15 years, 20 years out, you see that the rate of recurrence for lobular cancer starts to tick up. And so these patients think that they are potentially in the clear. They're off their medication, they're living their lives again, and then all of a sudden get hit with a cancer recurrence. These recurrences can also be really symptomatic because the way that the cancer shows itself or likes to involve the body can be in unusual locations.

And so when I talk to my patients about where might my cancer come back, we're often focusing on the lungs or the liver or the bones. And lobular cancer does like to go to those places, but it also likes to go to the inside of the stomach, inside of the intestines, lining of the heart, lining of the lungs. And so again, these symptoms may not be the things that patients or doctors are thinking about as classic cancer recurrence symptoms. So by the time somebody's thinking about it, the symptoms may be really progressed and the patient may be quite miserable from these symptoms.

And then a lot of those diagnostic challenges that apply at the beginning of the breast cancer journey can also apply to metastatic disease, where these single file cells can be really hard to see on something like a CAT scan. And the cancers grow slowly so they might not light up on a PET scan. And that poses a lot of challenges when a patient is feeling unwell, but all of our data is telling us there's nothing there to be worried about. And so really I think it's a unique perspective from a physician awareness standpoint and also a difference in the way patients have to think about their symptoms.

Dale Shepard, MD, PhD: Tell us a little bit about some recent research that you've conducted, looking at differences between these two types of cancer.

Megan Kruse, MD: A lot of breast medical oncologists feel that there's this difference between lobular and ductal and we see it day in and day out. But what's disappointing in the literature is there's just not that much there to support that. And so the research that we'll talk about today actually came about as I was having a discussion with a couple other breast cancer investigators over coffee at one of our national meetings. And we were talking about some of these ideas, and wouldn't it be nice to be able to pool all of our information together across the institutions that see a lot of lobular breast cancer so that we can have bigger numbers and try to figure out if there are subtle trends in the way this disease presents, the way we treat it and what the outcomes are?

And so that's really how we started thinking about working in a collaborative way between myself as an investigator at Cleveland Clinic and then a couple of my colleagues, one at Ohio State University and one at UPMC, or the University of Pittsburgh Medical Center. And we termed ourselves the Great Lakes Breast Cancer Consortium. And what we all did was we looked at all of our cases of breast cancer over a period of almost 30 years. And in that timeframe, we were able to see over 30,000 cases of breast cancer, the majority of them ductal cancers as you may expect, but actually a nice large number of lobular cancer patients. And it allowed us to really look with greater detail at these patients, who they are and what their cancers look like.

Dale Shepard, MD, PhD: And so what were some of the notable findings?

Megan Kruse, MD: So what we found, as I kind of mentioned originally, what our clinical experience was, was that the lobular cancers really showed themselves at later stages when they presented. So it was more common to see larger tumors with lobular compared to ductal. We also saw more lymph node involvement with lobular cancers compared to ductal cancers at diagnosis. And because these patients had more advanced cancers, they were getting more aggressive therapies, so there was more mastectomies given to the lobular cancer group than in the ductal cancer group.

The thing that was challenging, though, is we did see that these cancers were slower growing cancers overall, they were lower grades. So there was this mismatch between how aggressive they looked based on the size of the tumor and the lymph node involvement versus what the biology looked like when you looked under the microscope. I think the most important part of our findings, and the thing that we're still struggling to understand and know what to do about, is that we did see that the survival, unfortunately, for patients with lobular cancer was worse over time compared to those patients with ductal cancer.

So even though when you looked at the ductal cancers from a genetic biologic standpoint, they were more risky, we had high-risk tumors six times more commonly than the high-risk lobular tumors, the survival for the lobular cancers at that 15 and 20-year point that we were talking about earlier was actually 10 percent worse for the lobular group compared to the ductal group. And we don't really know what to do with that. I think this is where we need to take our next steps forward to figure out what kind of meaningful treatment approaches or diagnostic approaches can we use to improve those numbers.

Dale Shepard, MD, PhD: So we can talk a little bit about both, but let's talk first about the treatment itself. Any preliminary thoughts on from the data how we should be treating patients differently based on the biology?

Megan Kruse, MD: Yeah, so that's a great question. I think one thing we'd like to dig into a little bit more, so we know that less patients in the lobular group received chemotherapy, and I think that that has a lot to do with this idea that biologically it's less aggressive, so chemotherapy may not be that helpful. We did see a trend overall in both groups that less chemotherapy was used over time. And I think that has to do with our ability to refine who actually needs chemotherapy. But we don't actually know the details of those treatments that the patients received down to the level of what drugs, how long. And those details I think are going to be the most important to figure out where we can go from here, because I can envision that over this 30-year period, even the anti-estrogen therapy that would be standard for those patients diagnosed in 1990 would be very different from those diagnosed in 2015, for example.

And then the other thing that's curious about that is because these recurrence events are taking so long to happen, you just wonder what would happen to this group over time if you continue to follow them. Would we see this gap get even bigger? So I think that from a treatment standpoint, it'll be a little bit challenging to know from this data what may be meaningful, as the standards of care have really changed over time. But I think we can do the best we can, looking at the types of medications that are available maybe in each era of treatment and seeing how those cohorts of patients have done. And that's data we haven't pulled quite yet.

Dale Shepard, MD, PhD: And I guess something that as you look over a 30-year time period, of course now genomic therapies and immunotherapy approaches, is there a thought that these two types of breast cancer might behave differently?

Megan Kruse, MD: Absolutely. So that was one of the things that I'm really excited about is that now that we have access to genomic data, we can see some emergence of different trends for lobular breast cancers versus ductal breast cancers. And for the lobular breast cancers, there are a couple key genetic changes that we see. And actually there's some interest in targeted therapies that are available in other malignancies that we may be able to apply to lobular breast cancer and really start to make it unique in its treatment path compared to ductal cancers. And that is data that we wouldn't have had, I think, even 10 years ago. So more information there and getting more samples of these cancers over time, even comparing the original tumor versus a metastatic site, if we can, can be very, very meaningful.

Dale Shepard, MD, PhD: Tell me a little bit about some trials or drugs that you're excited about.

Megan Kruse, MD: I am hoping to have a few clinical trials up and running for our lobular breast cancer patients in the next year or so. And my goal is to have a trial across each of the situations that a patient with lobular cancer might find themselves in. So for example, can we do better with diagnosis? Are there different imaging studies that maybe we can take advantage of now to really accurately stage a patient and help them with the refinement of their treatment modalities?

And one there that I'm particularly excited about is something called FES-PET. And so you can think about this imaging technology, instead of having a fluorinated glucose molecule that we use to find where cancer is, this would be the fluorinated estrogen molecule. And so knowing that most of these cancers are estrogen receptor positive, this test can hopefully better define where lobular cancer cells are in the body. So that could help us in two ways: That could help us when we first diagnose these patients to get a better sense of, first of all, who has spread outside the breast and who doesn't.

And then we could also hopefully better refine the size of the cancer in the breast itself. But more so, and I think more impactful, is determining the involvement of axillary lymph nodes from the outset, because this could have a very meaningful impact about which patients need medical therapy before surgery, and how do we actually manage those axillary lymph nodes from a surgical perspective when a patient goes in for their first operation? So I think that that has huge potential, and it's technology that's actually already available right now.

It's only used in select situations for metastatic patients, but I think if we could potentially move it up earlier that it could be really beneficial for patients. And a couple other thoughts and ideas, I think it would be nice to better monitor response to treatment. So there I'm thinking about patients where we still use chemotherapy before surgery for lobular cancer, even though we're not really sure how well it will work. Some patients, because of the size of their tumor, just need chemo to try to shrink it down as best we can before going to surgery.

And it'd be nice to have a test as we were going along in real time that could tell us how well it's working. So we're trying to create a clinical trial here that we'll use circulating tumor DNA to hopefully help inform and guide that decision, where if we're getting a great response, we keep going, and if we're not getting a response, maybe we switch to some other either available therapy like an endocrine or hormone-based therapy, or could we go to some sort of novel targeted therapy? So those are situations that I hope that we'll be able to dive into more in 2023.

Dale Shepard, MD, PhD: And then I guess with FES-PET, I guess is there perhaps a thought that these women that come in and say, something's not right, and our traditional imaging pushes them down the course of time to get other imaging, may be a little more sensitive way to find these?

Megan Kruse, MD: Absolutely. That would be my hope. And then we could detect it earlier and then start on treatment earlier before there's some more obvious complication from the cancer that makes us aware that the cancer's there. I think it will hopefully help patients have better quality of life and get treatment going faster.

Dale Shepard, MD, PhD: One of the things that we do here at the Cleveland Clinic, and a number of other places do as well, are care paths. And as you see a patient and you have a certain situation and a diagnosis, standardizing treatments. And so what have you been doing, or what are you planning on doing to differentiate the therapies, the follow-up, the management of these patients?

Megan Kruse, MD: This is actually a great point, is that there are really no good national guidelines for the treatment of lobular cancer. As I mentioned before, we just kind of lump it in with hormone positive cancer in general. And I think there are some potential pitfalls there. And my hope with developing a standardized approach to treating these patients and having something published is that we can go back and look at our experience and say, did this work? Did this not work?

Where was it challenging? How did it help us? So it should improve that clinical flow and also give us a natural route to develop those research questions. But I think it also gives attention to lobular cancer as its own unique entity. And so when we're seeing these patients in clinic, we'll stop and say, oh, I think I should reflect on the care path to see if there's anything there that maybe I don't use day-to-day but I really should think about.

And so it's in its early stages of development. I think we're actually very, very close to have this on the Cleveland Clinic website. Right now we've focused on early lobular breast cancer diagnosis, getting patients through their diagnosis, surgery and initial medical therapy. And that path really incorporates a unique preference for breast MRI. I think breast MRI as of right now seems to be the best imaging modality that we have to stage patients before they go to the operating room. It's still not that great for axillary nodal staging.

We know we miss axillary nodal involvement about 30 percent of patients who at surgery are found to have nodal involvement. So again, I'd love to improve from there. But right now, I think there are patients who would benefit from that sort of technology that aren't getting it. So the idea would be to get that early on in the diagnostic process, so the patient doesn't necessarily have to come see their surgeon and then have the test ordered, which will delay care further.

And then the other hope is that once we're through the surgical piece, or even if a patient needs medical therapy before surgery, could we do some adaptive evaluation to decide what kind of therapy a patient gets before surgery? So there I'm thinking about using different genomic assays to determine how biologically aggressive is the cancer, and would that allow us to, say, select chemotherapy versus endocrine therapy before surgery? And is there any advantage of that to the patient in terms of what surgery is they're eligible for, and the extent of surgery that they end up going through?

So I think that those are two of the unique parts of the care path. And then of course, as we have these trials up and running, we'll get those plugged into the care path too, so that in the natural flow of things, as many lobular patients as we can have participate in research, we'd love to get them involved.

Dale Shepard, MD, PhD: And I guess along those lines that, I mean, you've certainly embraced lobular breast cancer as an interest and clearly sounds like there are nuances and it's less common. Are there particular patient characteristics, certain types of patients that would benefit from seeing someone like yourself or a place that specializes in lobular breast cancer?

Megan Kruse, MD: I do think so. I think all patients with lobular breast cancer, because it's such a unique entity and because there's still so much we don't know, if a patient has the ability to be connected with a site that has experience with this type of cancer and expertise in it, or is interested in furthering our knowledge of it, I think it only benefits them as well as the doctors that treat lobular breast cancer for that engagement to happen. And truthfully, when I was getting to know this disease space and learning about it, one of my best educational tools was through the Lobular Breast Cancer Alliance.

And their website has lots and lots of information about the disease, but also about clinical trials that are open and different centers that have investigators and clinicians that are interested in lobular breast cancer. And I think that as a community of sort of lobular advocates, that we should harness that power. Because a lot of what you hear is, oh, it's not that common. We're not going to be able to study it, or it's not really a priority for this research or that research because there's not that many people. But when you take 15 percent of the number of breast cancers we see in the United States every year, that's still a very, very large number, and it's really meaningful for the patients participating. So I think if a patient has access to a site where there's a lobular investigator or research programs to take tissue samples, blood samples, it would be phenomenal for as many patients to participate as possible.

Dale Shepard, MD, PhD: Well, Megan, you've provided some great insight for us today. Thanks for being with us.

Megan Kruse, MD: Thanks so much for helping us spread the word.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

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