Welcome back to an introduction to breast cancer. I'm Dr. Anees Chagpar. I'm so glad you chose to join us today. Over the last few sessions, we were talking about breast cancer, and really approaching it from a global perspective. We looked at the epidemiology of breast cancers, some of the risk factors, even things that we could do to prevent breast cancer. But, what exactly is breast cancer? How do we classify it? A lot of people talk about different types of breast cancer. And to be honest, I'm always a little bit confused when people use that term, types of breast cancer. It really depends on how you classify things. So some people will talk about invasive or true cancers versus in situ or pre-cancers. Other people will refer to types of breast cancer by the histologic type. That is to say, the cell from which the cancer arose. Other people will look at molecular subtypes, particularly in the current era of genomics. And yet other people will talk about grade and stage is being different types of cancer. And then some people will talk about particular types of presentation. So people who present with inflammatory breast cancer or Paget's disease. For my part, I like to keep things really simple. So let's look at the basics of breast cancer so that no matter what type of cancer people are talking about, you understand what they're talking about. Let's go to the drawing board. If we look at the breast, the breast is made up of ducts, and lobules. All of these ducts go to the nipple, and the purpose of those ducts is to carry milk that's produced in lobules for the purpose of breast feeding. But we know that outside of that context, the breast is a source of potential malignant transformation. In other words, a place where cancers can occur. Now most breast cancers, about 80 to 85% of breast cancers, come from the ducts. And about 10 to 15%, come from the lobules. Now, there is tissue in between as well, this is called the stroma. And, you can get cancers in the stroma as well. Think about what's in the stroma. The stroma is made up of everything other than epithelial tissue. So epithelial tissue refers to those cells that line the ducts and the lobules. The stroma is supporting tissue. So fibrous tissue, fatty tissue, blood vessels. In the stroma, we get what are called sarcomas, predominantly, and we're not going to talk about these sarcomas. What we are going to talk about when we talk about breast cancer are epithelial cancers, which are what we call carcinomas, which is another word for cancer. Now remember, we said that 80 to 85% of all breast cancers come from the ducts. Think about the ducts like pipes. If you went to the hardware store, and you bought a brand new iron pipe, and inside that pipe, you sprinkled a little bit of corrosive. Now, it's still a brand new pipe. So that corrosive has no time to work. If now, you put water down one end of the pipe, the was will go out the other end of the pipe. Because it's still a brand new pipe, and that corrosive has had no time to work. But if you let that corrosive sit there for a while. So that corrosive is sitting in that pipe. And time passes, and it rains. And that corrosive is going to have a chance to corrode through the pipe. Now you get an old, rusty, corroded thinned out pipe that's got little holes in it. So now, if you put water down this end of the pipe, the water could leak out those little holes. It doesn't have to, but it could, it depends on how big the holes are. Well cancer works exactly the same way. This first situation is what I call a pre-cancer. It doesn't leak, it doesn't spread, it doesn't go anywhere, it doesn't do anything, but given time, it could turn into this situation, which is what I call a true cancer. Now true cancers have the ability to spread. Why? Because while it's quite true that in your body, there aren't really iron pipes. But this barrier is what's called the basement membrane. And the basement membrane is important for one big reason, and that's because the basement membrane is what separates the ducts from blood vessels and lymph vessels, which then are the portal through which these cancers can spread. Okay, so true cancers have the ability to spread, they don't have to, but they could. Precancers don't have that ability because they're confined above the basement membrane. Now, if it were just that simple, we would be done, but there are a lot of synonyms to all of these terms. So precancers are also called in situ, in situ means inside the pipe. And their also called intraductal cancers. Think about anything that has an intra prefix. Intra-governmental affairs, intra-mural sports. Inside the ducts. True cancers are called invasive because they invaded that basement membrane. They invaded the pipe, or infiltrating. Because they infiltrated through the pipe. So that's a nice analogy to kind of give you a sense of the two main distinctions in terms of breast cancer. Precancers which are localized and don't have the ability to spread. We often also call this stage zero, and true cancers, which have the ability to spread, and those are higher stage, one through four. We'll get to that in a minute. So let's go back and look at the difference between invasive and in situ cancers. Invasive are also called infiltrating. They can be anywhere from stage one to four, depending on how big they are, and where they've spread to. They've invaded that basement membrane, which gives them access to the blood vessels and lymph vessels, and allows them to spread. As opposed to in situ cancers, in situ cancers are also called intraductal or DCIS. DCIS stands for Ductal Carcinoma In Situ. So remember, it comes from the duct, it's a carcinoma because it's an epithelial type cancer, but it's in situ inside that pipe. They're also preinvasive These are Stage 0 cancers. They have not invaded the basement membrane and have no capacity to spread. Well, when we think about breast cancers, the other thing to think about is where they came from, the cell of origin, and this is often called the histologic subtype. Histology is what the pathologists look at under the microscope when they look at the architecture and the cells of origin of these cancers. Remember that the two main histologic subtypes for carcinomas of the breast are those that come from the ducts, which are the vast majority, 80 to 85%, and lobular, those that come from the lobules of the breast, 10 to 15%. Now in general, ductal cancers and lobular cancers are treated exactly the same way. And their prognosis, that is to say, how well patients do when they have these cancers, is identical when controlled for stage. That is to say, that a Stage 1 ductal cancer will be treated and have the same prognosis as a Stage 1 lobular cancer. So what's the difference? Lobular cancers are what I call the sneaky cancer. They're sneaky because they tend to follow a single file pattern. I'm not sure how well it projects here, but you can see that these cells in the lobular pattern follow this single file pattern, whereas the ductal cancers tend to clump. If we go back to the drawing board here, ductal cancers do this. The cells all join together in a clump, whereas lobular cancers will follow a single file pattern. And so you can imagine that if you had a lobular cancer and a ductal cancer, in both situations, you may think that the cancer is this big. But in truth, the lobular cancer tends to be bigger than you anticipate. It's a sneaky cancer because it follow this single file pattern. So we've talked about in situ and invasive and we've talked about histologic subtypes. You'll often find those terms put together. So if you're reading a pathology report, for example, you'll find people talk about invasive ductal carcinoma or lobular carcinoma in situ. And so that way you'll see that those terms are really put together, all right. But in the current era of genomics, we have been able to look at cancers in much more detail. Now we have molecular subtypes, so as we look at cancers, we're able to really look in depth at them to see what receptors they express. That tells us what things turn on a cancer versus what things turn off a cancer. And that becomes important in terms of how we manage these cancers and treat them. There are three main receptors that we look for. The first is called Which is the estrogen receptor. And we talked a little bit about estrogen receptor when we talked about prevention, and we talked about selective estrogen receptor modulators. Remember? The second receptor is the progesterone receptor. Again, another female hormone that affects breast cancer cells. And the third is a receptor called her2. So if we think about a cancer cell, on the surface of the cancer cell there's receptors that are fed by estrogen and progesterone. These are female hormones. And then there are receptors for her2. Her2 is a tyrosine kinase, which is just a fancy name of saying that's the type of receptor that helps to take signals from the outside of the cell to the inside of the cell to make them behave abnormally. In our very first session, we talked about cancer being an abnormal, dis-regulated growth of cancer cells. And all of that is mediated by this signaling that happens. So when we think about these receptors, we know that it affects how these cancers replicate in terms of their DNA, and how that really gets disregulated in terms of cancer. So back to molecular subtypes. The combination of these receptors gives us a sense of how these cancers behave. And there are four main subgroups. Okay, there are more subgroups being developed all the time as we increase our knowledge about genomics, but let's keep it simple. Luminal A cancers are those that express And/or PR, so they're Or PR positive, and her2 negative. That's the most common subtype. The Ki67 is a marker of proliferation. So these tend to be fairly well-behaved. They don't have very rapid turnover. It's a good thing that this is the vast majority of cancers we see, over 50%. Luminal B are also estrogen and progesterone positive, but they also express her2. Or they may have a higher proliferation index with a higher Ki67. The her2+ subtype, as you can imagine, are those that really express her2. And they're negative for the estrogen and progesterone receptors. And then the basal-like are ones that are negative for all three receptors. They're Negative, PR negative, and her2 negative. Many of you may have heard about these, often referred to as triple negative breast cancers. So why do we care? Why do we care about these subtypes? We care for a few main reasons. The first is that prognosis varies based on the subtype. And the second is how we treat these cancers also varies. So if you have a cancer that's fed by estrogen and progesterone, that's great news, because we have drugs that can block that estrogen. You already know about some of them from our prevention talk. We can use tamoxifen or other selective estrogen receptor modulators. Or we can use aromatase inhibitors in post-menopausal women. For patients who are her2 positive, that's good news too, because we have agents that are specifically designed to block her2, drugs like trastuzumab or pertuzumab. We'll get more into detail about those when we get to our treatment lecture. The other way that we can talk about breast cancer is in terms of grade and stage. Now it's really important that you understand the difference between grade and stage. These are two entirely different concepts. Grade is what do these cancer cells look like under the microscope? Are they poorly differentiated? That is to say they deviated so far away from the normal look of the tissue. Or are they well differentiated? They look pretty much like normal breast tissue, but they are cancer cells. Stage is not what they look like under the microscope, but more how they behave. How big is this cancer. Has it gone to the lymph nodes. Has it spread all over your body? The distinction is critical. You can imagine that we worry more about stage then we do about grade. Now certainly, anybody would want a lower grade tumor, than a higher grade one. But if you had your choice between high stage low grade, or a high grade low stage, you'd prefer the latter. Why? Well, it's kind of like you'd rather have somebody who looks terrible, but is really nice, than somebody who is very dapper, but somebody like Bernie Madoff. It's that kind of distinction. So grade is what the cancer cells look like under the microscope, stage is how the cancer behaves. In terms of stage, we use a classification called the AJCC staging system. This is the American Joint Commission on Cancer, and they stage all kinds of cancers. For breast cancer, there are four stages, as for most cancers. Stage 0, you already know about. These are the ones that are inside you. On the staging system you can see that these are referred to as T I S. They tend to be node negative, and M zero, not metastasized anywhere else and you know why that is now too. Because those insitu cancers haven't gotten the ability to invade pass the basement membrane. They don't have access to the lymph vessels or the blood vessels, so they can't go anywhere else. Stage 1 are the cancers that are a little bit bigger, so up to two centimeters, but still don't really have any lymph node metastases. So remember, even though a cancer may be invasive, it invaded the basement membrane. It doesn't mean that it spread to lymph nodes or other parts of your body. These cancers are classified as stage 1A. And even if there are microscopic deposits, micrometastasis in the lymph nodes. These cancers are still Stage 1. So remember, even if cancer has gone to a lymph node, it's not the end of the world. We'll talk more about that when we get to treatment. As stage increases, it increases because of two main factors. Either the cancer is bigger, so T2 is two to five centimeters, T3 is more than five centimeters. Or there are more lymph nodes that are involved. N1 is having one to three positive lymph nodes, N2, four to nine. N3, 10 or more. The more lymph nodes you have that are positive for cancer, the higher the stage. But so long as the cancer is just confined to the breast and the regional lymph nodes, primarily in the arm pit, you still have local disease. It's only when cancers get outside of that spectrum, when they've started to go to the brain, or the bones, or the liver, or the lungs, that you get distance metastasis. Distant metastasis is down here, N1, and that is stage four breast cancer. Prognosis in terms of how well patients do long term is really dictated by their stage. Well, we've covered a lot of ground talking about the basics of breast cancer today, but there are a few other things that I want to point out. Special types of breast cancer. So some people may talk about about male breast cancer, Paget's disease, which is really presenting with an excoriation of the nipple. It's kind of like, if you were riding your bike and you fell and you scraped your knee, well it looks kind of like that, except people have scraped their nipple and this is associated with an underlying breast cancer. Other skin changes can also be significant for breast cancer. One of the most aggressive kinds of breast cancer that we see is something called inflammatory breast cancer. This often presents like an inflamed red breast, kind of like mastitis, an infection that many women get while they're breast feeding. Except this isn't an infection. It is a rapidly progressive and very aggressive breast cancer. Locally advanced breast cancers are a cousin, which just means a really bad breast cancer that can fungate out through the skin. We'll talk more about all of these special types of breast cancer in another lecture but I wanted to give you just this teaser so that you'll stay tuned. Thanks so much for joining me. Until next time, this is Dr. Anees Chagpar.
