HER2-positive breast cancer: preoperative therapies

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Julie Fisher, MD: I would like to discuss typical treatment pathways for patients with HER2-positive breast cancer. As your sister mentioned, we tend to have a fairly low threshold to achieve chemotherapy, again, in conjunction with these HER2 targeting drugs. Our reason for this is knowing that untreated HER2-positive breast cancer wants to be an aggressive player. Our way to fight this will usually be chemotherapy combined with targeted HER2 treatments, and we find ourselves hitting them, frankly, even for quite small tumors. For someone who hasn’t had surgery and presents with HER2-amplified breast cancer, and in your case it was palpable, we know we’re going to use chemotherapy. We know we’re going to be using some flavor of targeted HER2 therapy. The initial question is: should we start with preoperative chemotherapy or do we start with surgery and continue with postoperative chemotherapy?

There are different things that inform this decision making. Sometimes if a tumor is very small, is not palpable, and we are satisfied that it is not involving the lymph nodes, we can start with an initial surgical approach. However, generally when we are faced with a larger palpable area we often want to start with targeted chemotherapy / HER2 therapy. Our reasoning behind this is manifold. First, starting with treatment allows us to reduce or reduce disease; it offers us the possibility of reducing the size of the breast tumor. For someone who has suspected or documented lymph node involvement, this gives us the opportunity to treat, or hopefully even eradicate some of that disease in the lymph node. This in turn can result in less aggressive surgery, which is a good thing. Probably as important if not more important to me than the medical oncologist is knowing that when we start with preoperative chemotherapy, then we are able to determine then, well, how well has that chemotherapy worked? The way we can determine this is to see what the effect was on the breast when the surgeon takes the patient to the operating room.

Sometimes chemotherapy and preoperative treatments can achieve what we call a complete response. The surgeon comes in, goes to the clip or tag that was left to mark the spot, removes it and finds that any disease has been eradicated in the breast; the chemo killed it all. This is a complete answer. Other times we get a partial answer, which is also self-explanatory; chemotherapy killed much of the cancer, not all of the cancer, and whatever is left behind the surgeon removes. However, this full or partial response gives us a wealth of information about how we expect chemotherapy to work anywhere, and then it influences how we treat cancer after surgery.

I keep talking about these mysterious drugs targeting HER2; the first drug to appear was trastuzumab. The main brand of this drug is Herceptin, and it was in 2005 that it was introduced. At the time of its introduction, it was under study with administration over a period of one year; mainly we still do. Some studies have attempted to compare 6 months to 12 months of Herceptin. 12 months is still the norm in most cases, so we are looking at a year of therapy. We will adapt the postoperative treatment, the type of HER2 targeted therapy that we use, to the type of response that we have observed to the preoperative chemotherapy. Preoperatively, different treatment regimens can be used. The original studies that demonstrated the benefits of Herceptin used a chemotherapy backbone that included a drug called Adriamycin [doxorubicin]. It’s still a good diet but in our center we tend to stay away from it in most cases. Diets that have a taxane backbone, drugs like Taxol [paclitaxel] and Taxotère [docetaxel] are incredibly effective and have less cardiac toxicity than the combination that uses Adriamycin.

We are talking about, what will be the preoperative regimen? Again, the one I tend to hit the most and the one you get is a four different drug program: it’s 2 chemotherapy drugs coupled with 2 drugs targeting HER2, our old friend Herceptin and its drug cousin Perjeta [pertuzumab]. We’re going to put these 4 drugs together, and it’s given every 3 weeks for a total of 6 preoperative treatments. We see each other after each treatment for 2 main reasons. One is for me to see how you are feeling and assess what kind of side effects you might be experiencing, and try to step in with all the help I can offer depending on what is going on. . The second is to perform a physical exam to make sure the treatment is doing what we hope and expect it to do. Again, most cancers will respond to chemotherapy; cancer rarely develops or progresses with treatment. It happens, and when it does, we have to pivot and change gears quickly. It is important that this exam be part of the program.

Transcription edited for clarity.


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