September 9, 2013

Dr. Weintritt: Hello. Good morning.

Gregory Dennis: Good morning. Welcome to Breast Cancer Dialogues. I’m Gregory Dennis and we’re here today with Dr. David Weintritt, a breast surgeon and founder of the National Breast Center in Alexandria, Virginia. Thank you for joining us today Dr. Weintritt.

Dr. Weintritt: You’re so welcome.

Gregory Dennis: We want to ask you today about a recent article in the Journal of the American Medical Association titled Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement. We’d also like to talk a little bit about breast cancer and molecular subtyping. Can you summarize for us the background and reasons for this article by Dr. Laura Esserman in JAMA?

Dr. Weintritt: Sure, Greg. I think I can. First of all, I think it was very helpful to shed light on the need to recognize that not all breast cancers are the same and therefore the next step beyond that, is they shouldn’t be treated all the same. There’s been a conception that every breast cancer case is going to have an identical outcome, therefore lack in the resources, surgery, radiation, chemotherapy will need to be applied and that’s not the truth. Some patients will have a much less aggressive course. And so, we need to be more aware of how to determine what type of cancer is present and create a plan that’s more appropriate for the patient and not treat them as a group or as a whole.

Gregory Dennis: That’s quite an interesting development. Tell us a little bit more about the role of genomic testing which is also referred to as molecular subtyping and the role that plays in preventing over-diagnosis and over-treatment of breast cancer.

Dr. Weintritt: Well Greg, the secret to everything always lies in the genetics. There are certainly some cancers that occur because of an increase risk that the patient carries from birth, but that’s a genetic issue. But once a cancer happens, whether it was something that was driven by a high risk situation or whether it was spontaneous mutation, a type of cancer and the behavior of the cancer is going to be driven by its genes. So the key – if we’re going to try to not only categorize cancers as high-risk or low-risk so that we don’t over or under-treat them, but also look into options of trying to develop a more or greater variety of treatments so that we can be more specific in treating cancers, we need to be using that concept of genomic testing or molecular sub-typing. Now, there are tests fortunately today that give us that capability. The one that provides the depth of knowledge is a test called MammaPrint which is one version of genomic testing. And by looking at the human genome and finding the genes that are consistently associated with breast cancer, as well as identifying one of the four different molecular sub-types of breast cancer, you’re able to tell with each individual patient what their likely outcome is and how aggressive their treatment course should be and in some case, fortunately, how the course of treatment should not be aggressive at all.

Gregory Dennis: Tell us more about what you mean by how, in some cases, the course of treatment should not be as aggressive.

Dr. Weintritt: Greg, if you look at known outcomes from patients with certain gene signatures – and again, I’m talking about when you analyze the cancer recognizing that all cancers are going to be different in certain ways but the differences are going to be very subtle and sometimes based upon the over or under expression of certain genes, you’ll find not an insignificant but quite a large group of patients with breast cancer, will have a very low risk that the cancer will ever spread. I think this is one of the key things that the author is trying to shed light on and that not all women with breast cancer should be worried about their cancer spreading or should be worried about potentially dying of breast cancer, and therefore should be going through treatments like chemotherapy. This low-risk group has a less than 5% chance over a five year period of time of their cancer ever spreading or showing up anywhere else. Therefore, we see in that group there’s no need for extensive chemotherapy regimens or treatments of that nature because the risk is already low, whether they receive chemotherapy or not.

Gregory Dennis: I see. Now, you mentioned MammaPrint which I guess helps determine the risk of recurrence of the cancer. Tell us a little about the BluePrint test – and these again are part of the Symphony panel of tests.

Dr. Weintritt: Well, it’s been well recognized that there are four basic types of breast cancer. Each of which – functions very differently. There are – the Luminal group comprised of Luminal A and Luminal B, there is a group that over-expresses a receptor we refer to as HER2, and there is a group we refer to as Basal, otherwise known as triple-negative. The molecular sub-typing will categorize patients into one of those four groups. They’ll be one of the four. They won’t be a mixture. That’s very important because responses to things like chemotherapy, need for chemotherapy, or in some cases no need for chemotherapy will be divided differently amongst those groups. And so, paying attention to the molecular sub-type will make the treatment plan much clearer for patients. I think it actually helps patients understand why we make the decisions, which is very important in this process.

Gregory Dennis: How is the introduction or the use of genomic testing and molecular sub-typing different from what used to happen? This is new information or relatively new types of information you’re dealing with. How is it different from the way you used to understand and diagnose breast cancer?

Dr. Weintritt: So in the past – and I’ll be honest, I still think in the present in some situations, although not in my practice. If you looked at a group of 100 women with breast cancer, you would know that roughly 40% of them would benefit from chemotherapy based upon the chance of some members of that group having one of the higher risk types. However without specific tests such as MammaPrint, it would be difficult to know which 40 women were the high-risk in that group. So the default decision would be, in order to not under-treat anyone, is to recommend treatments like chemotherapy to almost the entire group. While I don’t disagree with the concept of “Let’s make sure patients are not under-treated,” now that we’re able to more accurately identify patients, we can now begin to pull the high risk members out of that group with an accurate selection process. We can also fortunately not over-treat. Very important – we have this array of options for treatment, that we make fit the patients’ needs. The concept of over-treatment and under-treatment is very important. Nobody wants to undergo chemotherapy. If we identify accurately that it will be beneficial to their survival, they see the reason to do it and they’re very compliant. On the other hand, if we have a pattern of recommending chemotherapy to every patient with breast cancer, we’re going to become a little disingenuous in applying those treatments and unfortunately many patients will receive it that don’t need it. So, that is the huge benefit of advancements like molecular sub-typing and genomic analysis; so that women can receive treatment plans that are much more accurate.

Gregory Dennis: I think there’s a natural tendency among woman who have breast cancer to say, “Let’s do everything to be sure that we’re safe, to be sure that we’ve taken care of the cancer,” but I gather there are problems with over-treatment as well. How do you see that issue? What are some of the dangers of over-treatment and why should we be concerned? As well as to not under-treat, why should we be concerned to not over-treat?

Dr. Weintritt: Well Greg, you have to be very careful when we make departures from what previously were considered standard recommendation. One of the first things I’ll do is put myself in that position or try to imagine what it would be like to have a cancer diagnosis and determine, what do I think is the best course for it. So, I don’t disagree. I certainly can understand that previously, when women were not aware of or were able to understand, and have people explain to them what their outcomes going to be, that they would say, “Give me everything. Give me whatever is available because I don’t want to face this recurring or ever have to deal with again.” But now that we have the ability to select those groups, we’re able to explain to them not just our gut feeling but scientifically how they’re able to avoid over-treatment and avoid chemotherapy.

In getting to the second part of your question, the reality is, patients have a very small chance, but a real chance of potentially dying as a result of chemotherapy. There are secondary malignancies that can occur. There are situations where patients can become anemic or susceptible to infection during chemotherapy. There are quality of life issues that can occur with chemotherapy, neuropathy, infertility – many things that don’t just happen in the moment but can linger on. So, it’s a very important balance about understanding the risks and the benefits and not applying something in a situation where it’s not going to help.

Gregory Dennis: Thank you. I think we’ve covered most of the key points. Is there anything else regarding the article in JAMA or the issues of over-diagnosis and over-treatment we should touch on today?

Dr. Weintritt: Yes, I would like to make one last statement at least in that the article comments on the need to begin taking patients into low risk group and high risk group. I commend the author because that is in some cases a significant change in mindset. When you look further also in the article, it mentions that our screening process has increased the number of favorable cancers but has not lead to a significant increase in the diagnosis or the detection of unfavorable cancers and they’re viewing that as a potential failure of screening. But I think the appropriate way to look at it Greg, is that since we’ve developed so many less invasive techniques for diagnosis and treatment of breast cancer, finding lower risk types earlier allows women to go from the beginning to the finish of their treatment process much faster, with fewer side effects, and a greater quality of life. So, the screening process has benefited those patients. Now, it would be a complete dishonor to not deal with the other half of that where you have a group of women that are still presenting with later stage breast cancers that are potentially lethal. So, we use again this concept of molecular testing, genomic testing – tests like MammaPrint to decode the genetics of the cancer to use them to develop new therapies so that we can make an impact for that group as well. So, screening is not a failure. There are ways that screening has been successful for allowing women with less invasive cancers to undergo shorter courses and less invasive therapies. But, we also have to recognize that it’s not perfect for some of these other types of cancers. It does not mean we should abandon screening, but we have to continue to aggressively pursue the genomic testing concept and utilize it to find new ways to treat women with more aggressive cancer types.

Gregory Dennis: Great point. Thank you very much Dr. Weintritt. It’s been a pleasure talking to you here today on Breast Cancer Dialogues and we appreciate your taking the time.

Dr. Weintritt: You’re so welcome. I hope that it has been helpful information and we’ll enjoy to continue to see the evolution of this concept and more appropriate therapies for women now and in the future. Thank you very much.