Welcome back to an introduction to breast cancer, I'm Dr. Anees Chagpar. We're almost near the end of the this course. I know, I'm disappointed too. But hopefully, we've learned a lot over the last several sessions. We've learned a lot about breast cancer and the fact that we have a variety of tools in our toolbox to treat breast cancer, but remember that breast cancer is not a singular disease. A lot of the principles are the same, but there are some special presentations. And today, we're going to focus on those. So let's get started. There are few key special presentations that I want to highlight in today's lecture. The first is inflammatory breast cancer. I've referred to this in some previous lectures as being a really bad cancer. And if you remember nothing else, I want you to pay particular attention to this one. Why? Because this is the worst form of breast cancer that we deal with. The second is Paget's disease. Another simple variation, but one that actually has a very good prognosis. And for the gentlemen out there, your not off the hook. Remember that breast cancer occurs in men too, so we'll give you a little bit of time talking about male breast cancer. We'll talk about breast cancer and pregnancy. What happens when breast cancer comes up at the most inopportune time? And finally, we haven't spent a whole lot of time during this course talking about distant metastatic disease. We've focused a lot on how to treat cancers that we can treat and potentially cure, but we haven't talked about distant metastatic disease. So we're going to do that today, as well. So starting with inflammatory breast cancer. Remember, this is a picture I would love you to memorize. This is what inflammatory breast cancer looks like. We often talk about this peau d'orange appearance. For those of you who aren't French, that's orange peel. The skin gets thick, it gets red, it gets inflamed, it can be painful and you get these little pits that show up, because the dermal lymphatics, the lymphatic system in the skin gets plugged up with cancer. Now, the picture on the left clearly looks like an orange peel. Most of you could probably pick that one up, but the picture on the right, maybe a little less so. It can be subtle, but it's something that I don't want you to miss. Oftentimes, this can be confused with mastitis. People think, well, this is just a little breast infection and that's fine. If it doesn't go away with antibiotics, you need to be thinking about inflammatory breast cancer and it's important that you make that diagnosis. On imaging, this can be really sneaking. Here you see a MRI, an ultrasound and a mammogram. And oftentimes, it's not one that screams out of you and says, here I am, I'm a cancer in this person's breast. Sometimes, the only sign that you'll see on the mammogram or ultrasound or even MRI Is skin thickening. So pay attention to that. These can be associated with an underlying mass, but not always and so having a high degree of clinical suspicion is really critical. Now, how do we make the diagnosis? Well, tissue as always is the issue. We do this with a little punch biopsy, a little biopsy of the skin. This can be done in the office and what are we looking for? We are looking for dermal lymphatic invasion. This is pathognomonic. Pathognomonic means if we see this, it is inflammatory breast cancer. Dermal lymphatic invasion is exactly what it sounds like. Its cancer cells plugging up the lymphatic cells in the skin. And here, you can see both a gross view as well as an up close view of what that looks like with these cancer cells really in the lymphatic space. Now when we talked about stage of disease, remember we had said, it's based on tumor size and lymph node status and distant metastases. Well, 30% of these patients present with distant metastatic disease at the outset. So, it's important that you do that metastatic workup to make sure that they don't have distant metastases when they first walk in the door. So check their bones with a bone scan, check their lungs and their liver with a CT scan of their chest and abdomen. But even if they don't have distant metastatic disease, so they're not stage IV, anybody who presents with inflammatory breast cancer is stage IIIb at least. That's because we know that inflammatory breast cancer is really bad news, but that isn't to say that we can't treat it. We can and here is where that whole multidisciplinary management that we've talked about over all of the previous sessions really comes into play. So we want to treat these patients with chemotherapy upfront, neoadjuvant, before surgery. You can consider doing a biopsy of the lymph node before that even starts, so that you know what this patient's lymph nodes status is before you ever treat with chemotherapy. After that neoadjuvant chemotherapy ends, you want to wait three to eight weeks before you start your surgery. Why? Because you don't want to do surgery right after the last dose of chemotherapy, because blood counts invariably are low and patients are not feeling fit. On the other hand, you don't want to wait more than eight weeks, because you don't want to give this cancer a chance to regrow. So you have to time your surgery in what I call the sweet spot, three to eight weeks from the last dose of chemotherapy. Now, what kind of surgery? Remember back to the surgery lectures, we talked about partial mastectomy. We talked about total mastectomy. We talked about skin sparing options with immediate reconstruction. We talked about giving patients choices. Not in this one, because inflammatory breast cancer is by definition, cancer that has got into the skin. You don't want to spare the skin and you don't want to do a partial mastectomy. So these patients by definition require a conventional mastectomy, a total mastectomy where they are left flat. Now you can consider reconstruction down the line, we'll get there, but the fresh modality of surgery is a conventional mastectomy. What about lymph nodes? Remember, when we talked about lymph nodes? We had talked about setting the lymph node biopsy. This is one circumstance in which a sentinel lymph node biopsy does not work and you can imagine now that you now about sentinel lymph node biopsy, why that would be the case? Remember in sentinel lymph node biopsy, we talked about injecting a radioactive tracer and a blue dye into the breast? And that those track through the lymphatics to get to the lymph nodes, so that we can identify which are those sentinel or first draining lymph nodes. Well, what happens if the lymphatics are all plugged up with tumor? Well, clearly the tracers won't get to where they need to get to. So we know that with inflammatory breast cancer, the false negative rate, the chances of not finding the right lymph node, when you do a sentinel lymph node biopsy are very high. So sentinel lymph node biopsy is not something you want to do in these patients. And these patients will therefore require an axillary lymph node dissection. Now, I'm going to test your memory a bit. Do you remember what a conventional mastectomy plus an axillary node dissection is? What term we use for that? Yep, a Modified Radical Mastectomy. So all of these patients require a Modified Radical Mastectomy. Now, these patients are at high risk of cancer coming back. And you'll remember from the radiation therapy lecture, that we talked about Post-mastectomy Radiation Therapy being needed in people who are at very high risk, to reduce the chances that the cancer comes back in the chest wall. So all of these patients need Post-mastectomy Radiation Therapy. Now, remember when we talked about reconstruction? Well, reconstruction and radiation, that's not a great marriage, especially in the immediate interface. So, after radiation is done, these patients can then let their skin recover. Oftentimes this'll take six months to a year and consider reconstruction down the line. If these patients have Positive disease or HER-2 positive disease in that intravening time, they are going to continue to get their targeted therapy. Whether that's hormonal therapy for Positive disease or drugs like trastuzumab or pertuzumab for HER-2 directed therapy. So, this is a fine example where you're really pulling together all of those building blocks that we've talked about over the last several sessions, so exciting. Well, let's switch gears to another skin manifestation of a breast cancer. This is Paget's disease. Paget's disease often presents with a scaliness of the nipple, kind of an excoriation. Like when you're riding your bike and you scraped your knee. This is the same kind of thing, except it looks like a straight nipple. And we still make the diagnosis based on the punch biopsy of the skin. This time, we're looking for Paget cells. Paget cells are these big cells. They've got a pale cytoplasm that's eosinophilic which means it's pink. The nuclei tend to be big. But the interesting thing with Paget's Disease is, unlike inflammatory breast cancer that is very aggressive, Paget's Disease is associated, oftentimes, with an underlying DCIS. Remember DCIS, ductal carcinoma in situ? That in situ disease is actually stage zero, so pre-invasive cancers. So, unlike inflammatory breast cancer, Paget's Disease has a wonderful prognosis. Many of these patients will still opt to have a mastectomy because the disease is located at the nipple. And so that nipple needs to be removed and often times the underlying cancer is in that central part of the breast. And so, by doing a partial mastectomy, you essentially create what we call a volcano defect, where that projection of the breast is lost because you kind of cored out the central part of the breast. So many of these patients will opt for mastectomy, although, not all. But, these patients can have skin-sparing procedures with immediate reconstruction, these patients can have a sentinel lymph node biopsy. And frequently they do not require post-mastectomy radiation therapy. Okay, what about the guys? Well, Male Breast Cancer is rare, but it still is there. Remember, 1% of all breast cancer occurs in men. So, guys need to be aware of this, too. Because men don't get mammograms, they often present late. They'll present with a lump or bloody nipple discharge, many of the things that women get. But often times because they lack the awareness of the fact that they too can get breast cancer, they often times undermine or ignore the symptoms that they have. Men will come in and say, aah yeah, I felt this lump but I thought I was just pushing a little bit too much at the gym. Newsflash, you can get breast cancer too, if you feel a lump or you have bloody nipple discharge or skin changes that are concerning, you should get these checked out. The treatment is often very similar to that of women. Except that men too, often times, will choose to have a conventional mastectomy. They're not usually interested in reconstruction. What about pregnancy? So it's a happy time, you're pregnant with a new bundle of joy, and you feel a lump in your breast. You go and you get it checked out, and you're told that you have breast cancer. This is, for many women who are pregnant, tragedy, but it doesn't have to be. You need to know that breast cancer in pregnancy is treatable, and there is something that we can do while still preserving the pregnancy and treating the breast cancer at the same time. Breast cancer occurs as one in every 3,000 pregnancies, and the management really depends on the trimester in which we detect it. So, surgery is safe in all three trimesters. In the first trimester, as in the other two as well, we want to be particularly careful to monitor the fetus. But we can do that and still maintain a viable pregnancy. What about chemotherapy? The newsflash is chemotherapy is actually quite safe, especially in the second to third trimester. People have done studies looking at women who have gone through chemotherapy in their second to third trimester. Their children are fine and don't have any cognitive or other problems even out to 18 years. Radiation, however, and hormonal therapy cannot be given during any trimester. But that's okay, because often times, after chemotherapy and surgery, you then deliver and you can have your radiation and hormonal therapy as you need to after you deliver. So it's important for women to know that we can treat breast cancer in pregnancy. It often requires really pulling into that multi-disciplinary team, the OBGYN, to really make sure that we're taking care of not just the mom but also the baby as well. But, the other question that often comes up, particularly for young cancer patients, and this doesn't matter whether they're young and pregnant or whether they're just newly diagnosed and young. Maybe they haven't had their first pregnancy yet. One of the questions that often comes up is well, after all of this breast cancer treatment, can I have a future pregnancy? And the answer is, yes, but. And the but here is, we need to be thinking about this beforehand. So, if you have a young cancer patient who is potentially going to have more children. You need to be thinking about how you can preserve her fertility, either with egg harvesting or taking ovarian strips or preserving embryos. Many of you may be near fertility centers that can help with this, but this oftentimes, needs to be done before chemotherapy is started. So it's important to have a conversation with your patient or for patients to have a conversation with their doctors to talk about fertility preservation, if you end up getting breast cancer before you've finished having all of the children that you want. Last topic, what about the unfortunate situation where you have distant metastases? The cancer is already spread. Now the most common places where cancer spreads outside of the breast and lymph nodes are the bone, the lungs, the liver and the brain and we talked about when we talked about staging how we look at all of these different sites. Bone scans, CT scans of the chest and abdomen. We don't often need to do any scans of the brain, because oftentimes, we only need to do those if people present with neurocognitive symptoms. But what happens if patients do have distant metastatic disease? Again, the treatment is primarily systemic. So we're going to give chemotherapy or for two directive therapy or endocrine therapy, really to get into that bloodstream to attack those cancer cells in the sites where they are. Radiation therapy can be helpful too, but really for palliation of symptoms. So it's used for brain metastasis, for example, for bony metastasis, but surgery, thus far at least has no role. Now there are clinical trials that are looking at, if we can achieve some control of these distant metastatic sites with systemic therapy and we still have cancer in the breast, would removing that primary breast cancer be of benefit? Still remains questionable, but clinical trials, as always will provide the answer. Now, palliative care is really important. Some people think that palliative care is hospice and the only time to involve palliative care is when there is no other hope. That's not true. Palliative care, more and more is being seen as part of the primary team. Now truly, their role increases as the primary team's curative treatment decreases, but it's important that palliative care is part of the team at the outset. Not because we think you're going to die, but because they have expertise that may be helpful. They often have expertise in terms of symptom management, in terms of goal setting, in terms of psychosocial distress. All of these things are important and so we know that, for example, in lung cancer involvement of the palliative care team early, actually improved survival rates. Go figure, so don't confuse palliative care with hospice. Hospice, however is important at the end of life and the transition from palliative care to hospice is something that the palliative care team can often help with as well. So that's bring us to the end of all of this special presentations. I want to reassure you that breast cancer continues to be a complex field, it's impossible to cover every possible scenario. Talking about these in your multidisciplinary teams really starts to harness all of the intelligence of all of the specialties as you look at different circumstances. But hopefully, this is giving you a bit of an overview. Until next time, this is Dr. Anees Chagpar.
