Invasive lobular carcinoma

Kellie Curtain [00:00:04] Let's be upfront about invasive lobular carcinoma. It's the second most common type of breast cancer, and yet it typically isn't easily detected on mammogram because it doesn't present as a lump in the breast. Joining us is breast surgeon Professor Bruce Mann. And we're going to discuss the different types of invasive lobular cancers, possible treatments and what the future might hold to assist earlier diagnosis. Professor Bruce Mann, welcome back to Upfront. It's good to have you with us again.

Bruce Mann [00:00:32] Thank you. Delighted to be here.

Kellie Curtain [00:00:35] So can you explain what invasive lobular carcinoma actually is?

Bruce Mann [00:00:40] Okay. Lobular carcinoma is a type of invasive cancer and it often comes up in pathology reports and people want to know what it means, what's the difference. It's a cancer that has a different appearance under the microscope and it has a possibly different cell of origin. And during the talk, we’ll work out, we'll talk about how it behaves a little differently. But in general, it's one of the subtypes of cancer. The two main subtypes are ductal carcinoma and lobular carcinoma. The simple way to think about that is that in the breast, there are lobules that make milk. There are ducts that take milk from where it's made to the nipple. The lobular carcinomas arise from the lobules. The ductal carcinomas arise from the ducts or the cells lining the ducts. Now, whether that is actually the case, I think there's there's still work to be done, but that's a simple way of looking at it.

Kellie Curtain [00:01:50] Okay, so invasive lobular carcinoma is actually the second most common type of breast cancer.

Bruce Mann [00:01:56] It’s the second of the invasive cancers. So we talk about pre-invasive carcinoma, DCIS, and the invasive cancers, the actual cancers. The most common is ductal carcinoma. They actually say ductal carcinoma not otherwise specified. So not one of the unusual subtypes. And then there's lobular carcinoma. The incidence, maybe 15 to 20 per cent of all breast cancers are lobular carcinomas.

Kellie Curtain [00:02:29] Is one more aggressive than another?

Bruce Mann [00:02:34] For a cancer of the same size and the same stage, they're about the same. It's not worse to have a lobular carcinoma or a ductal carcinoma. If one has to have a cancer, you would prefer it to be small. You would prefer it not to be in the lymph nodes. You'd prefer it to be low grade. They're the things that you really ‘want’ in inverted commas, whether it's ductal or lobular, doesn't matter too much.

Kellie Curtain [00:03:05] Okay, so lobular carcinomas can be difficult to see on mammograms. Can you explain why that is?

Bruce Mann [00:03:12] That's the issue. The lobular carcinomas, they tend to spread. They tend to be diffuse. So the cancer cells will spread through the normal breast tissue and they don't form a lump the same way as ductal carcinomas tend to. This is in general terms. There are lobular carcinomas that are little lumps, but generally the lobular carcinomas, they're diffuse so they can be widespread before the woman's aware that anything's changed or the change isn't so much a lump, but just a general change. And importantly, sometimes they're not seen on mammograms. So of the cancers where a woman's had a normal mammogram and then turns out to have a large cancer that is not seen on the mammogram or not appreciated, it's more common that it's a lobular carcinoma.

Kellie Curtain [00:04:07] Because it doesn't necessarily present as a lump

Bruce Mann [00:04:09] It doesn't form a lump ... no your words are exactly right, doesn't necessarily form a lump.

Kellie Curtain [00:04:15] Okay. So what are some of the other imaging tests that would assist diagnosis?

Bruce Mann [00:04:23] The standard tests are useful, so mammograms can be abnormal, often are abnormal. The abnormalities may be subtle. Ultrasounds again are often ... are sometimes fairly normal. Sometimes there they look like a typical breast cancer, but sometimes it's a diffuse change and it may be not appreciated that there is a change there.

Kellie Curtain [00:04:51] So.

Bruce Mann [00:04:52] And while the third one is an MRI. Again, MRIs are useful with lobular carcinomas and it is an area where the MRI may be more sensitive, may be more accurate than the standard mammogram and ultrasound.

Kellie Curtain [00:05:09] Okay. We're hearing more about research into the role of artificial intelligence and the use of computer algorithms to assist in diagnosis. So what exactly is this and how could it improve detection?

Bruce Mann [00:05:25] So I'm not a computer scientist. I'm not a specialist in A.I. But basically, the algorithms, the deep learning means that the computer is presented with examples of a particular condition. In this case, it would be a breast cancer on a mammogram, maybe a lobular carcinoma on a mammogram. It's shown many of them. It's essentially told this is what it looks like. It then analyzes them, compares them to normal, and it can identify ... the program can identify abnormalities that may suggest there's a cancer there. The work in breast cancer is that there is a lot of work's being done. It's making progress. And many of us expect that before too long, AI is going to have a role in assessment of mammograms. Exactly when, where, how, we don't know. But it could be that one of the things that the AI is better able to detect these subtle changes and maybe - it's just a maybe - that the lobular cancer is an area that it will help.

Kellie Curtain [00:06:36] So given that it doesn't typically present as a lump. Does it quite often results in that type of breast cancer being diagnosed further advanced?

Bruce Mann [00:06:49] That's the issue. When you asked earlier, is it worse? My answer was specific. It's for the same size, for the same nodes, it's no worse. But if it's less obvious, it can present quite, quite late. So.

Kellie Curtain [00:07:08] And is that what you're usually finding? I mean, given that it is harder to detect it, does it make sense that it is diagnosed later?

Bruce Mann [00:07:15] I don't think, when you say usually, I think most lobular cancers are found when they're fairly small. But of the cancers that are large, so throughout much of the breast at the time of diagnosis, lobular cancers are disproportionate. So more of those cancers are lobular than the number of lobular cancers overall.

Kellie Curtain [00:07:39] Are there any telltale signs, given, in the absence of a lump, is there anything that someone could look for?

Bruce Mann [00:07:45] I think this is where the advice of 'if something's not right, make sure it's checked properly.' A number of patients I've seen have reflected and they've essentially said, look, something wasn't quite right, but there wasn't a lump and I couldn't really feel something. And I'd had a mammogram last year and it was normal. So I thought it must be nothing. You know, that's a story that we hear a bit. So what can it be when I see someone who has the more advanced, the larger lobular cancer? It's often the whole breast. The affected breast is different from the other. But within that breast, there is no single lump. There's nothing to say, ‘Look, you know, here is the spot that's abnormal’ It's just the whole thing. Well, not always the whole thing. A larger area is more subtly different. So that goes back to the 'something didn't feel right, but I'm not sure what it was'. That's where we, as you know, the radiologists, the surgeons are aware and the women need to be aware as well.

Kellie Curtain [00:08:53] Okay, let's talk treatment of invasive lobular carcinoma. What are the ways that you treat it?

Bruce Mann [00:09:00] Okay, so one thing to mention before that is there is some suggestion that lobular cancer is more likely to be multi-focal, meaning if someone has a lobular carcinoma in, say, the left breast, that there's a significant chance of having a separate lobular carcinoma in the right breast. This is something that was sort of viewed as a fact when I was learning this stuff. More recently, the evidence doesn't really support it. So the idea that it's multi-focal, two foci or multi-centric to, or bilateral ... the idea that it is commonly bilateral or multi-centric is not supported. There are cases where it is, but similarly there are cases of ductal carcinoma where someone has two cancers.

Kellie Curtain [00:10:00] So if someone has been diagnosed with ILC in one breast they shouldn't panic and think, oh, they've missed it in a second.

Bruce Mann [00:10:09] They shouldn't panic. If someone has a cancer in one breast, the other breast must be closely assessed with appropriate examination and imaging because bilateral cancer can occur, but it can occur in any situation. As far as treatment, the approach to treatment is very similar to the approach with the ductal carcinoma. What we do is we assess the nature of the cancer. So that's the subtype, the receptors, whether it's HER2-positive or negative. We need to know exactly what we're dealing with. We assess how extensive it is in the breast and then we assess the lymph nodes, whether the nodes appear to be involved or not. Assessment in the breast is a little more difficult because as I said before, it's not so much a lump. It can be diffuse. And that's where extra imaging and potentially the use of an MRI scan prior to surgery or during the assessment can have a role. I don't think it's needed always, but it certainly is an important thing to think about.

Kellie Curtain [00:11:25] So we're talking like, for visual uses, like a little cluster?

Bruce Mann [00:11:30] When you see it under the microscope, there can be, cells can be lined up. Single file cells spreading through otherwise normal tissue and that can be over quite a large area. So often there is the main cancer, you know, the central part, and it's just lots and lots of abnormal cells. But when the pathologist examines the area around it, rather than being normal breast tissue, often they can point out little rows of cells where it's a sort of streaming away feel or it looks like it's streaming away from the main cancer. So assessment of the true extent is important and can be difficult. But as far as treatment is concerned, once you've determined the extent, the treatments that we use in lobular cancer are much the same. Surgery is important, radiation is often important. Most lobular cancers are hormone sensitive. So they usually, the cells usually, not quite always, but usually, have the receptors for oestrogen and progesterone, the female hormones. So hormonal blocking treatments, and there's various types, are a very important part of treatment of lobular cancer. And we could come back to that a little. Most lobular cancers are HER2-negative. So that's the oncogene. HER2-positive cancers can be treated with drugs like Herceptin. That is sometimes useful in lobular cancer. But most lobular cancers are HER2-negative. Most lobular cancers are grade 2. And reminding everyone, the grade is how aggressive cancer looks like under the microscope. It goes 1, 2 and 3. Three is more aggressive. Most lobular cancers are grade 2, but some of them are more aggressive and are grade 3. And they're the ones where chemotherapy is more likely to have a role. Whereas the standard grade 2 lobular cancer; chemotherapy may have a role. It's something that the oncologist will always consider and discuss. But it is less important than in some other types of cancer.

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Kellie Curtain [00:14:11] Is there, as far as the treatment, is it common given that it is in a row and therefore coming over a slightly possible larger area ... are they more likely, say, with a grade 3 to treat with chemotherapy first before surgery?

Bruce Mann [00:14:29] That's a great question, because as you and listeners will know, one of the things that is changing in breast cancer is we are more often using primary systemic therapy, either chemotherapy or hormonal therapy. The judgment is for lobular cancers is fairly similar to other cancers. Because lobular cancers are often very hormone sensitive. So strong ER and PR , oestrogen receptor and progesterone receptor. Turns out that many lobular cancers are relatively chemotherapy resistant. So they're not as sensitive to chemotherapy. Now this is where it always gets difficult. But if you've got a case, a woman has a cancer that is likely to be chemotherapy resistant, we are generally fairly reluctant to start with chemotherapy. You don't want to leave the cancer there, treating it with something to which it may be resistant. So some lobular cancers we certainly do use neoadjuvant [therapy]. And they, as you point out, the grade 3, if they are HER2-positive, that's the ones where Herceptin can be used. We will often use pre-operative chemotherapy. But lobulars are one where primary surgery remains, remains a ... probably the most common approach.

Kellie Curtain [00:16:05] And given again, that it's not necessarily a lump, or that it's a bit more spread out, is a lumpectomy usually what happens or do you see more mastectomies?

Bruce Mann [00:16:16] Again, these are exactly the questions that need, that people need to be aware of. Because of its nature. If they are larger and you can't be sure of how extensive, breast conservation is less likely to be successful. Which means either the initial assessment is such that it's apparent that mastectomy is the only reasonable approach, or alternatively, the cancer may appear small enough so that breast conserving surgery is possible. But at surgery, if we find that the margins are positive, if there is additional disease, it may be that as a second procedure we need to recommend and do a mastectomy.

Kellie Curtain [00:16:58] So let's talk the hormonal blocking option.

Bruce Mann [00:17:04] Yes. So hormonal therapy, we use it, hormonal therapy. But your wording is correct. It's hormone blocking. It's either blocking or [a] reduction of circulating levels. We often refer to it as endocrine therapy, but in common parlance, it will often be called hormone therapy. That confuses people because they hear, well, hormone replacement therapy may increase the risk of breast cancer. Now you're going to give me hormone therapy. Go figure. But it is actually, it's a hormone blocking therapy. The main drugs are tamoxifen, which interferes with the way that oestrogen interacts with cells,…

Kellie Curtain [00:17:45] And forces menopause, yes?

Bruce Mann [00:17:48] Not so much. So, oestrogen is effective in women before menopause. It can lead to an alteration in periods… It certainly can lead to some menopausal side effects. So you know, the symptoms that a woman may suffer - it's ‘may’, not ‘always’ - may suffer while on tamoxifen can be very similar to menopausal symptoms. But so tamoxifen will, it will interfere with the way that oestrogen acts on the cells. The other drugs, so they're called the aromatase inhibitors, anastrozole and letrozole and exemestane are the common ones, often referred to by their trade names of Arimidex,Femara. Those ones, they reduce the amount of oestrogen circulating in a woman after menopause. So that's hormone reducing. And if there's less circulating, there's less that could act on cells. And then the final method of hormonal treatment, or hormone blocking, for premenopausal women is actually to do something to render that woman menopausal, so suppressing ovary functions.

Kellie Curtain [00:19:07] So you do take into account the woman's age?

Bruce Mann [00:19:08] Age and menopause status: pre or post-menopausal, really very important. So there's a lot of introduction there to the question of hormonal blocking. So endocrine therapies are a very important part of treatment of lobular cancer. We use, we are more likely to rely on those therapies than [chemotherapy], so more of that and less chemotherapy on average.

Kellie Curtain [00:19:41] Because of the resistance?

Bruce Mann [00:19:42] Because they may be chemo resistant. There is a possibility. I'm not sure how strongly to put it. There was a big study that was done comparing the effectiveness of tamoxifen, the traditional treatment, with the aromatase inhibitors. The new ones, Arimidex and Femara. And an analysis of the trial. Overall, the trials said that the AIs, the aromatase inhibitors, are slightly more effective at preventing breast cancer recurrence than tamoxifen, overall. And that has led to a lot more use of the AIs. There was an analysis of that paper, of the patients in the paper, that suggested that the women who particularly gained, benefited from the AIs rather than tamoxifen are those with lobular cancer ... One analysis goes so far as to say that most of the advantage of AIs over tamoxifen is in the group with lobular cancer. We don't know that for sure. These analysis have to be looked at very carefully. But many of us use that to say that if a woman has a lobular cancer that is higher risk, that the aromatase inhibitors are important. That there's enough evidence to suggest that those women should be given aromatase inhibitors in preference to tamoxifen. It's a broad statement, doesn't apply to everyone. And, as always, ask your oncologist. But it is out there and many of us think there might be something to that.

Kellie Curtain [00:21:34] Why, do you know - if you know - is it resistant to chemotherapy?

Bruce Mann [00:21:46] As a general rule, cancers, that is that the strongly hormone sensitive cancers tend to be  slower growing. They divide a little less, they divide less rapidly, and cells that are dividing less rapidly tend to be resistant to chemotherapy because chemotherapy generally works during cell division.

Kellie Curtain [00:22:09] What about other targeted treatments or potential?

Bruce Mann [00:22:13] So the targeted treatment, Herceptin, Perjeta, those drugs. They are highly effective, but only in HER2-positive cancers. The classical lobular cancer is HER2-negative and therefore those drugs don't have a role. But every so often we certainly see a HER2-positive lobular cancer and we will treat them with those medicines in the usual manner. You know, we will often ask the pathologist [as] this is unusual, and the answer is yes, it is. But it is a HER2-positive lobular. They can go together.

Kellie Curtain [00:22:51] OK. So what about the chance of recurrence? Is it greater with lobular cancer or any different?

Bruce Mann [00:22:59] Stage for stage they're the same.

Kellie Curtain [00:23:02] Okay.

Bruce Mann [00:23:03] So a small node negative lobular cancer treated conventionally. It's very unlikely that it will recur. A large multiple node positive lobular cancer ... highly treatable. And we treat that, we aim to cure. But we know that unfortunately, women who've had and been treated for those cancers have a higher risk of recurrence. Receptor positive cancers often recur late. So depending on the type of cancer, some of the more aggressive, the receptor negative cancers, particularly the triple negative cancers, if they're going to recur, those often occur usually, not only often, usually occur in the first five years. And late recurrences are uncommon. With lobular cancer, like other highly hormone sensitive cancers, less likely to recur early. But there are a small number of cases that can occur, can recur many, many years after diagnosis.

Kellie Curtain [00:24:14] Okay. And as we know, with triple negative, that's very much seen in younger women. Do we tend to see a demographic with lobular?

Bruce Mann [00:24:27] Good question. I didn't do my homework well enough. I think the distribution is the same. I think it roughly matches the population. So more in older women. Seeing a lobular cancer in an older lady isn't particularly surprising. In a younger woman? It's a standard distribution.

Kellie Curtain [00:24:55] And the final word then on lobular cancer?

Bruce Mann [00:22:02] Well, it's hard to give it just a final one word.

Kellie Curtain [00:25:05] Have 10.

Bruce Mann [00:25:06] There's a couple of points. One of them is what we talked about. If the breast feels different, if something's wrong, make sure you're treated, assess, treated seriously and assessed properly.

Kellie Curtain [00:25:17] Because I'm sure many people would not be aware. Everyone is just so well educated on feeling for lumps.

Bruce Mann [00:25:24] Yeah. So that's important. Now, breasts often, you know, women come in, you know, something feels wrong. We do all the assessment and then we cannot find anything. And with years of follow up, there was nothing. So it doesn't mean there will be. But that's point number one. Point number two is when, if someone unfortunately has a cancer and it's a lobular cancer, it's not the end of the world. These are highly treatable, successfully treated in most cases. The treatment might be just a little different. But it's not a disaster to have a lobular cancer. Well, it's no worse having a lobular cancer than any other cancer. And they're my final words.

Kellie Curtain [00:26:09] Thanks, Bruce, for chatting with us. And as you mentioned earlier, if you have any individual concerns, please contact your health team. The opinions of our guests are welcome, but not necessarily shared by BCNA. And be sure to take a look at our website for some great resources and links to more information on invasive lobular carcinoma. This episode was made with thanks to Cancer Australia. I'm Kellie Curtin. It's great to be upfront with you.