That’s another advance in the past few years in which these have been compared with each other. Many clinical trials have shown that some of the oral preparations, like clodronate or Boniva, might be used for osteoporosis, and they’re in clinical trials to see whether they’reas good as the IV preparations. I mentioned that if a breast cancer is not hormonally responsive, or if there is a larger burden of tumor and the physician does not think the response from an aromatase inhibitor or other hormonal therapy would gain a good time of stability for the breast cancer, we will often move to chemotherapies. I listed six commonly used chemotherapies that are used in both early-stage breast cancer and advanced breast cancer. That’s another advance in the past few years in which these have been compared with each other. Many clinical trials have shown that some of the oral preparations, like clodronate or Boniva, might be used for osteoporosis, and they’re in clinical trials to see whether they’reas good as the IV preparations. I mentioned that if a breast cancer is not hormonally responsive, or if there is a larger burden of tumor and the physician does not think the response from an aromatase inhibitor or other hormonal therapy would gain a good time of stability for the breast cancer, we will often move to chemotherapies. I listed six commonly used chemotherapies that are used in both early-stage breast cancer and advanced breast cancer. 

Many, many clinical trials are being done. It’s a very exciting time to see what schedules are working better than the previous schedules and what some of the new ones are that are coming out. I want to just point your attention – these are a lot of molecular vocabulary words, but the bottom line is that many of these named chemotherapy agents work in different ways to stop the cell from dividing. Some get into the DNA of the cell, whether they interrupt the way cells pull apart when they divide – that’s what a microtubule helps to do; it’s machinery that helps the cells pull apart when they divide – or they fool the cells in the backbones of DNA that it needs to replicate itself. Chemotherapy is used either in combination, if the physician thinks a rapid response needs to be made and if a patient can handle the side effects of it, or one at a time. Many studies have been done and clinical trials have shown that the response rate can be just as good with one type of chemotherapy at a time as with combinations. But, again, it’s non-specific. All of the chemotherapies, despite how good they are, have arelatively non-specific way of affecting cells that are rapidly turning over. That’s why there are a lot of different problems with side effects. Some highlights on the Living Beyond Breast Cancer website, in terms of recent clinical trials: people are looking at different permutations of how the chemotherapy is given. Is it better to give it once a week, every three weeks, depending on the type of chemotherapy? Can we combine the chemotherapy with some of the targeted agents? That’s what I was mentioning before that I’ll show you as well. 

These three that are highlighted on the website, what I’m just going to show you is that, for example, you’ll hear a lot about taxanes: paclitaxel, which comes from the bark of a Pacific yew tree, believe it or not; and docetaxel or Taxotere, which has been widely used in breast cancers, both early stage and advanced stage. … In the metastatic setting, it’s been found that Taxol given at a lower dose but closer together – once a week [as opposed to every three weeks] – not only has a better side-effect profile but also yields a greater ability to keep breast cancer from coming back or from progressing such that chemotherapy needs to be changed. This was presented at a major meeting of the American Society of Clinical Oncology about two years ago. This is one we use in the clinical [trials] a lot – Taxol as a single agent once a week, for example. Taxotere or docetaxel has been compared with Taxol by itself to see whether the time to progression is improved. These have similar sideeffect profiles, which we will get to in terms of neuropathy and lowering of the blood counts. A specific study that was presented in the Journal of Clinical Oncology did show that the proportion of patients who had not progressed was higher on the Taxotere than on the Taxol. Those particular doses, though, were compared at the every-threeweek regimens. That’s another option that has emerged recently in clinical trials. Taxol is known to have some side effects of causing allergic reactions. The tubing has to be very specific. We need to make sure patients get pretreatment with things like Benadryl, Tylenol or steroids to cut their risk of an allergic reaction. Recent research has sought to develop Taxol in a better-delivered system.

Taxol also comes in a preparation with an albumin coating. Albumin is a blood protein that carries all kinds of different hormones and proteins in our bloodstream anyway. That is called nanotechnology – a nanoparticle where Taxol is encapsulated in albumin. It causes better delivery to tissues with fewer side effects and less need for prophylaxis against allergic reactions. [The albumin-coated Taxol] is called Abraxane commercially. It also has been compared with Taxol by itself, the every-three-week dose, and it has shown a better median time to progression. Abraxane can be given first; it also can be given after, if a breast cancer has become refractory to the taxanes. Several clinical trials have shown that Abraxane is also a very good option. I’m going to have you keep this part in mind, because we need a lot of supportive therapy in terms of its side effects as well: Because more drugs in the nanoparticle can be delivered to the breast cancer, more side effects in terms of the neuropathy may occur. They may be a little bit more severe than the taxane alone but may last a shorter time. I mentioned targeted therapy. Not only do we want to use chemotherapy to try to combat breast cancers, but wealso want to become more specific in targeting emerging new knowledge about breast cancers. The HER2, or human epidermal receptor, family is a very important family of receptors that has been shown to be overexpressed on breast cancer. It’s a family of four receptors. Basically, a sheet of fat lobules comprise the membrane of a cell, so it’s the wall of a cell; it’s the coating of a cell. They just fit together to keep things out of the cell.

 HER2 is overexpressed in 25 percent to 30 percent of breast cancers. This little receptor sticks out from the surface of the membrane. It’s sticking out, ready to capture growth signals and translate that through the core inside the cell to a whole mechanism and a whole cascade of factors that will tell the cell to grow. The HER2 being overexpressed often gives the cell multiple signals to keep growing. There is an antibody to HER2 called trastuzumab, or Herceptin, that you’ve heard a lot about in the news, I’m sure. When this antibody binds with that receptor on the cell membrane, it fools the receptor and the cell cannot translate those growth signals, so the growth will hopefully at least slow down, if not stop. The advances that were made and published in the New England Journal of Medicine back in 2000, 2001, have shown that … progression-free survival is higher when trastuzumab is combined with Taxol, for example, in HER2-positive metastatic breast cancer. That is a standard of care. This is just to highlight that we’re trying to incorporate more targeted therapies, either adding to the chemotherapy or using them alone. An oral compound that is in clinical trials and hopefully will come out soon targets both the HER2 and the HER1. It’s lapatinib, an important compound that also has prolonged time to progression, or TTP. Clinical trials have looked at it in combination with an oral chemotherapy called capecitabine. This is in HER2-positive breast cancer. Again, breast cancers all act differently, and in this particular situation of HER2-positive breast cancer, we can use that.