Welcome back to an Introduction to Breast Cancer. I'm Dr. Anees Chagpar. We've talked a lot about breast cancer treatment over the last several sessions that we've had together. We've talked about surgery, and when I talked about surgery I was specific about talking about radiation as well. You see, surgery and radiation therapy combined are both local therapies that we use for the management of breast cancer. Today, we're going to dig a little bit deeper into radiation oncology. Let's get started. Back when we talked about the different stages of breast cancer and the treatment modalities associated with each, we talked about radiation therapy being a big maybe with any stage of breast cancer. And the reason for that is this, radiation therapy is a local therapy. In metastatic disease, so stage four breast cancers radiation can be used to specifically radiate a distant metastatic site. A spot in the brain or a spot in the bone. In the other stages of breast cancer, 0 through 3 it really is combined with surgery to reduce local failure, to reduce the chances of the breast cancer coming back in the breast. Well let's talk more about how that works. So the purpose of radiation therapy is really for local control. It reduces the chance of cancer coming back in the breast after a partial mastectomy. And even after a mastectomy, where the entire breast has been removed, radiation therapy can reduce the chances of the cancer coming back in the chest wall. Remember when we talked about surgery, we said that even after a mastectomy you can't remove every single solitary cell. That's where radiation therapy comes in for patients who are at very high risk, reducing the chances that one of those left over cells might turn into a cancer. So the big question is, but does it really translate into a survival benefit? Now, many of the early studies that I showed you when we talked about surgery didn't demonstrate a survival benefit. But now, the early Breast Cancer Trialist Meta-Analysis which I'm showing you here, demonstrates that there actually might be a survival benefit. In the sense that when we pool data from many, many, many clinical trials. So having now data from thousands upon thousands of patients, when we put all of that data together, we're beginning to see that actually reducing the chances of local recurrence might actually translate into a survival benefit. Intuitively that makes sense, but it's one of the reasons why we focus now more on radiation therapy really to help us to achieve good local control. Now, there are a variety of different types of radiation. The work horse is what we call whole breast radiation therapy. This is where patients get radiation to the entire breast. There are two separate regiments here that are commonly used. The first is given about 5 days a week for 6 weeks, it's about 15 minutes of time, and radiation really doesn't hurt. You lie down on what ostensibly is a table and radiation beams are shot at the breast. Yes, it's more complicated than that and there's a lot of physics that goes into it, but that's essentially it. Now there is a newer form of radiation often called Canadian hypofractionation, with a hat tip to the Canadians who really started this technique. Which is the same form of external beam whole breast radiation therapy. But can be delivered in a much shorter period of time, often over three to four weeks. Now, another form of radiation is what's called accelerated partial breast irradiation. Accelerated because it can often be given over a week, twice a day, for about a week, but the partial is the key ticket here. It only treats part of the breast, the part where the cancer was. And yes, that's where most recurrences occur but not all of them. There are different varieties in this category as well. Catheter brachytherapy, we're essentially skewers of brods are place across the breast. That are loaded with this radioactive substance that can then kill off cancer cells in their path. Because many people don't like the catheters, there was devices invented that essentially are balloons that can be placed in the cavity of the partial mastectomy. And a iridium seed can be placed in the middle of that balloon that then gives off a radiation field over about a centimeter, again partial breast irradiation. And then people who were really cool with physics started to look at how they can modify the physics to give external beam radiation in a three dimensional way to replicate that form of accelerated partial breast irradiation as well. So here there are no skewers, there are no catheters, just fancy physics that can still deliver that radiation to a part of the breast. Now APBI, as it's often called has been used and data are still mixed as to whether it is comparable to whole breast radiation therapy or not. Many radiation oncologists have their own preferences with regards to whole breast radiation therapy versus APBI. And then there's another form of radiation that's even shorter and this is Intraoperative Radiation, where the radiation is given in one shot right in the operating room at the time of the surgery. That sounds pretty cool, but it has a number of disadvantages as well. One is that it's only partial, so just to that area. And the second is that you may not know what the margins are around that cavity that you've taken out. Remember back to the surgery lecture, we said that that margin was really important. So suffice it to say that there are a variety of techniques that are in the toolbox of the radiation oncologist in terms of how to deliver this radiation. We're going to talk more in this lecture about whole breast radiation therapy, because this really is the workhorse, the mainstay of therapy for radiation oncologists treating breast cancer patients. Now as this picture demonstrates, that whole breast radiation therapy is given in what are called tangents. So you have one tangent field that comes this way across the breast coming out over here. And another tangent which comes this way across the breast coming out over here. So essentially, tangents on both sides really addressing the whole breast. Why is this important? Remember back to when we talked about lymph nodes and we said, we used to take out all of the lymph nodes? Now we take out some of the lymph nodes, those sentinel lymph nodes. Well there are now data that even if a centinal lymph node is positive if patients are getting whole breast radiation. Because of that tangent that goes across and covers the lower two thirds of the axilla or the arm pit, many times these patients don't require an axillary dissection. More and more however, there are data coming out that there may be benefit in patients who have disease or suspected disease in lymph nodes for irradiating these. So our radiation oncology colleagues are getting particularly aggressive, especially in cancers that are of a higher stage to radiate regional fields. The axilla, the superclavicular field, the inferior clavicular field, the internal mammaries. And so it's important to talk to your radiation oncologist about whether or not those fields are going to be captured. And here are data hot off the press from a recent randomized control trial called the MA20 trial. That was published in the New England Journal of Medicine that shows that when comparing whole breast irradiation to whole breast irradiation with again regional nodal irradiation. And so adding infields that cover those lymph node basins, that happens to do better. Not in all patients, there's still some controversy, but these data are compelling as well. Now, does everybody need radiation? So far, it seems that way. But the answer is maybe not. These are a couple of big trials that came out looking at particular sub populations of patients who do very well. In general, these are patient over the age of 70, who have smaller cancers who do not have lymph node metastasis in their armpit who often have estrogen receptor positive cancer that can be inhibited with drugs like aromatase inhibitors or tamoxifen. And the data suggest that these patients may not always require radiation therapy. Again, this is still controversial area some radiation on colleges will argue that even if you are over 70, if you are in particularly good health, we still want to reduce the chances of local recurrence and so adding radiation maybe advisable. On the other hand, if you are a patient who is older or may perhaps not be in the best of health, this suggest that we maybe able to avoid radiation therapy in these patients. What about radiation after a mastectomy? Presumably, we've removed as much of the breast tissue as we possibly can, so we've really minimized the amount of breast tissue that is there that could recur. But there are patients that are at particularly high risk, and it's important to remember that across clinical trials, post mastectomy radiation therapy has been associated with about a two-third reduction in the risk of chest wall failure. That is to say getting cancer back after a mastectomy. Where do those cancers usually occur? Right underneath the skin or right on top of the muscle layer. So how do you know if you're at particularly high risk, because clearly reducing 3% by two-thirds to 1% only gives you about a 2% absolute benefit. But if you had an absolute risk of 30% and you reduced that by two-thirds, getting that down to 10% is a 20% absolute benefit. It's important to remember the difference between a relative risk reduction and an absolute risk reduction. So how do we define who are going to be those patients who are at most risk for getting chest wall failure? It's the usual suspects. Patients who have larger cancers, bigger than five centimeters or who have many lymph nodes that are positive, often times more than four. Although the data here are mixed, some people will say anyone with a positive lymph node should at least be considered for post-mastectomy radiation therapy and certainly patients who have bad breast cancers. Inflammatory breast cancer for example, should all be offered post mastectomy radiation therapy. The British Columbia and the Denmark trials are really those trials that made us question whether even one lymph node being positive counts as benefiting from post-mastectomy radiation therapy. Because in those trials yes, they were criticized for a bunch of reasons that we won't go into here. They both showed a survival benefit with Post-Mastectomy Radiation Therapy. So something to think about. Now, with all the pluses of radiation therapy. We also have to think about the minuses or the side effects. What are those? Well for the most part, there what you would expect from any radiation. Think about when you're out in the sun. That's radiation too. Well, what would you get? You'd get a sunburn. You might get a little bit of redness, a little bit of tenderness, a little bit of dryness, the skin might peel a bit. It's the same kind of thing with radiation therapy. Sometimes it can pull in on the scar a little bit. Patients can get a little bit tired. The chances of getting a secondary malignancy or a cancer that is directly related to having irradiation exposure is very low. Usually in the order of one in 1000, or less. So while certainly it can happen, it's pretty rare. The other thing that can happen are these innocent bystander effects. What does that mean? Well that means that while we're trying to target the breast, underneath the breast are lungs and heart, your feeding pipe is in your thorax too. Might those be hurt by radiation? The answer is yes, but. And the but is that oftentimes, particularly with modern day radiation therapy, there's a lot of planning that goes into exactly how those fields are delivered. So before patients are started on radiation therapy, there's often this thing called a simulation. A CT scan where the radiation oncologist and the physicist plan out the dose that they're going to give and try to really tailor those fields just to target the areas that they want, and not the areas that they don't. Now they're never 100% successful, so there clearly can be innocent bystander effects but again, that's rare. And it's becoming more and more rare with newer techniques. So things like prone positioning that's where instead of getting your radiation lying flat on your back you get your radiation lying on your tummy. What does that do? Well it pulls the breast away from the underlying lung. Helps to prevent those innocent bystander effects in getting more lung or heart in the field. Intensity modulated radiation is a way of planning the radiation to block out the parts that you don't want to treat while treating the ones that you do. And deep breath-hold really stops breathing so you are able to make sure that you capture the radiation when the lung is out of the field of the beam versus not. These are interesting and exciting techniques. We'll see if we can't have an interview with one of our radiation oncologists here to talk more about these techniques. Can't promise yet but, I'll keep you posted. Until next time, this is Dr. Anees Chagpar.
