Health Topics

Candidates for Neo Adjuvant Therapy

Andrew Schorr:

All right. Let's put this in perspective and what's challenging and you are addressing in research. So what percentage of the women who are candidates for neo adjuvant therapy and receive it achieve the kind of complete response that Janell did?

Dr. Specht:

Well, that's the challenging part is that with our present chemotherapy drugs it's really only a minority of women, somewhere between eight and maybe up to 30 and sometimes 40 percent of women who will achieve the pathologic complete response. And predicting who will achieve that depends a little bit on the exact type of the tumor, but clearly we are not able to get that good response in all of the women, and certainly we have a lot of room there for improvement because what we would obviously like to see is that we can achieve a pathologic complete response in a much higher percentage of patients who are treated with this type of therapy.

Andrew Schorr:

So you have a research study that you are one of the main, principal investigators on, and that's the idea to adjust or add to the traditional approach for neo adjuvant therapy for these women to see if you can have a complete response in more women.

Dr. Specht:

Correct. So a number of investigators for many years have been looking at different regimens of chemotherapy and more recently what might be the best scheduling of the same drugs that are standardly used for breast cancer. And building on the work that was done by my colleagues here in the Seattle Cancer Care Alliance particularly Dr. Georgiana Ellis, Dr. Bob Livingston, and Dr. Julie Gralow, there has been a long history of studying a type of chemotherapy called continuous or metronomic chemotherapy where we give the standard chemotherapy drugs in a slightly different schedule, where we give smaller doses of the drugs but on a more frequent basis, daily or weekly as opposed to large doses of chemotherapy every two or three weeks.

And so we have this backbone of what we call the continuous chemotherapy that involves giving two drugs, a drug called doxorubicin and a second drug called Cytoxan or cyclophosphamide then followed by a third drug called paclitaxel, and we had this backbone that we knew worked quite well, but again we only achieved, we only saw that complete response in a minority of women. So our research, our present research study is adding an additional drug that isn't chemotherapy, but it's called a biologically targeted agent. It's a drug called sunitinib, or Sutent is the brand name. And one of the things that we have learned through our studies is that blood vessels are very important to the growth of breast cancer, the vasculature, how this tumor receives its fuel. And we know from other studies that have been done at our center that certain tumors can have a distorted blood vessel growth pattern, and those tumors can be particularly resistant to chemotherapy. This metronomic or continuous type of chemotherapy seems to have effects on blood vessels as well as actually killing the tumor, and so it was a logical step to add this newer agent called sunitinib to our backbone of chemotherapy to see if we can improve the rate of that pathologic complete response which means allow more women to have no tumor left at the time of their surgery.

Andrew Schorr:

All right. We are going to get much more into the science of it and explain more about this research and how you monitor it and understand how this drug you have been mentioning, which is approved for other cancers but not yet for breast cancer, how you are investigating it to see if it can help here. And it's very exciting research, and I know if women have questions, they can give us a call. Or you can send an e mail to us, patientpower@seattlecca.org. We will be back with much more of Patient Power right after this.

Welcome back to our live webcast sponsored by the Seattle Cancer Care Alliance. Andrew Schorr here as we are discussing neo adjuvant therapy for breast cancer and how research is adding a new drug to try to get a better result for more women who are affected. And also we are going to talk in a minute about the imaging that goes along the way to see how that drug therapy is working. You don't want to receive cancer medicine, believe me, that then you find out months later didn't do the job. You want to know. And we heard about that from Janell Sabol, and we will hear more from her doctor and researcher, Jennifer Specht, in just a minute.

Janell, I want to go back to you. So you are hearing about this science. Now, you were lucky, fortunate, whatever the right word is, you were one of the minority of women we heard who got this result where the cancer seemed to disappear. It's a whole scary process, but for women who are considering treatment, sounds like you have a lot of faith in Dr. Specht and where this research is headed.

Janell:

Absolutely. Absolutely. It's just, you know, you have to trust your doctor and know that you are in good hands.

Andrew Schorr:

And the Seattle Cancer Care Alliance, that's where you were diagnosed. How did the treatment go? Do you feel like you got good care?

Janell:

Absolutely. I got the best care that, anywhere, I think, by going there. I mean the people, the doctors there are so helpful and the nursing staff. It's just it's an amazing place.

Andrew Schorr:

I am going to ask you a real direct question, Janell. Do you feel that Dr. Specht and her colleagues saved your life?

Janell:

Absolutely. Definitely.

Andrew Schorr:

Dr. Specht, I know that's gratifying for you, and you are trying to help more and more women who are affected by this. When someone has this locally advanced, I think that's what you called it, breast cancer, so it's a larger tumor, so if I heard you right, if it can respond to the drugs, then they can be as well off as someone who just had a little itty bitty tumor, not that any size tumor is good. But it sounds like though that when you can have a result like Janell you can be very encouraged.

Dr. Specht:

Yes, that's true. When women or when patients present with breast tumors that are larger in the breast or when the breast cancer has already spread to the lymph nodes under the arm, in the axilla, we know that in general their prognosis for having a long term survival is lower than for those women who present with tiny tumors that haven't spread to the lymph nodes. And so that's one of the reasons why we offer them, oftentimes offer chemotherapy before their surgery because we are concerned that the disease even if we can't see that it has spread, that it may have already spread to other parts of the body that we have no way to detect on our normal studies like CAT scans and x rays and things. And so the idea of giving neo adjuvant chemotherapy is that we get chemo into the body more quickly, and the chemotherapy works everywhere in the body, in the breast, in the lymph nodes and also potentially to other places if there were one or two cancer cells that had already escaped to the breast and the lymph nodes.

Andrew Schorr:

Now, if someone's cancer is discovered and it's larger, does that necessarily mean the cancer is a more aggressive? And I know we will talk about inflammatory breast cancer, but apart from inflammatory breast cancer, does it just mean it was discovered later or does it mean that these cells are dividing more quickly?

Dr. Specht:

You know, it's a little bit complicated. As we learn more about breast cancer, we learn that there is actually probably several different diseases that we call breast cancer. So there are some, the majority of breast cancers probably grow pretty slowly, meaning that they change and grow slowly and that they might have been present in the breast for many months prior to the time that they were able to be diagnosed either by mammogram or by forming a lump that a woman might feel.

However, there are other types of breast cancer including the type that Janell had that do grow more quickly, and those are oftentimes breast cancers that are what we call estrogen receptor negative, and HER2/neu negative types of cancers. Those cancers grow more quickly, and they tend to have a more aggressive biology or again be more likely cancers to come back even after successful treatment. And so when a woman presents, depending on the type of breast cancer that she has, that can also help us in terms of guiding her on what the best therapy is as we look at these different types of breast cancer.

Andrew Schorr:

All right. And I just want to understand the type of breast cancer that Janell had was estrogen receptor negative, correct?

Dr. Specht:

Correct.

Andrew Schorr:

Where many older women, the more typical is estrogen receptor positive.

Dr. Specht:

That's correct. And what has been identified more recently in the last several years is the type of breast cancer that's now being called triple negative, and sometimes also called basaloid breast cancer. And this specific type of breast cancer is defined as one that grows more quickly. It usually is a high grade tumor, which is something that's assigned by the pathologist based on the appearance of the cells, and then it's also defined by the fact that it is estrogen receptor negative, progesterone receptor negative, which is another hormone receptor, and HER2/neu negative.

Andrew Schorr:

Wow. And we have talked in other programs about women when they are told they have HER2/neu positive breast cancer, we have had a drug that's really been revolutionary for a while, Herceptin, to target that situation. Triple negative has been more difficult I know traditionally. So now you are doing this research with Sutent. So tell us about this drug. It's approved for what other cancers?

Dr. Specht:

So Sutent or sunitinib is a drug that's called a tyrosine kinase inhibitor, so it's an oral drug that interferes with the activity of several types of, several specific proteins. The drug has been studied in a variety of different types of cancers but has been FDA approved for the treatment of renal cell carcinoma and for the treatment of a more rare type of tumor called gastrointestinal stromal tumor, or GIST.

Andrew Schorr:

Okay. I should mention, and correct me if I am wrong, but in medical oncology you are frequently taking a drug that was effective in one type of cancer, looking at it scientifically and saying is there a chance it could help in this other cancer situation. I had that very much in leukemia where there was a non Hodgkin's lymphoma drug, Rituxan, that was used, and it was effective for me. So that's exciting when there can be that transference.

Now, we talked a little bit about the idea of what these drugs do, anti angiogenesis drugs. I think this one would fit in there. There are others. I know some people and other cancers and even in more advanced breast cancer have heard about Avastin. So the idea, if I get it right, is that healthy cells have one pathway for blood supply, but cancer cells almost have sort of backdoor blood supplies they develop, and therefore since they have this separate system they develop, if you can just cut that off healthy cells can go on and still receive nutrition and divide properly. Is that right? It's kind of like there is this other, these bad guys, if you will, develop their own supply, and if you have drugs that can target that you can be successful?

Dr. Specht:

Yes, that's correct. We know that tumors and breast cancers in particular can be very dependent on pathways that involve the vascular, that involve vascular endothelial growth factor receptors and that the drugs like Avastin or bevacizumab, which is now an FDA approved drug, seem to work by interfering with blood vessel growth. And we know that tumors need blood vessels to supply them with nutrients in order for the cells to grow and divide, and so this class of targeted agents which really aren't chemotherapy but more biologic agents that target the blood vessels are gaining increasing importance in the treatment of breast cancer.

Andrew Schorr:

Well, let's talk more about that. So this drug Sutent then, or tell me the generic name again or the scientific name.

Dr. Specht:

It's sunitinib.

Andrew Schorr:

Sunitinib. I'm going to get that right. This is an oral medicine, you said, a pill. So tell us how often does someone take that? In your research study now how often would they take that? And then in a minute we are going to learn about how you monitor it.

Dr. Specht:

Sure. So Sutent is a drug that's taken once a day every day, and the way that we are studying it in breast cancer is to combine the Sutent with one of the standard chemotherapy drugs that we use called paclitaxel or also called Taxol. And paclitaxel is generally given by vein, intravenously, once a week. And for the purposes of this research study we are giving, women are taking the Sutent once a day for a period of 12 weeks while they are receiving the paclitaxel chemotherapy drug.

Andrew Schorr:

Okay. Let's talk a little more about that. So I want to help people understand about imaging. So Janell mentioned it about monitoring what therapy she received. So what do you do to see whether with the addition of this drug and the effect of the other drugs, the backbone you talked about, whether they are interfering with the supply of the cancer cells and then hopefully helping them die?