Welcome back to An Introduction to Breast Cancer. I'm Dr. Anees Chagpar. Today we're going to be talking about breast cancer prevention. So the last time we met, we talked a little bit about what breast cancer was, and the fact that this really was a global phenomenon, affecting millions of people all over the world. But wouldn't it be great if we actually could prevent this disease? When we left off, we started talking about some of the risk factors associated with breast cancer. Remember that some are modifiable, and some are non-modifiable. So while there are some risk factors that we can't do anything about, maybe we can prevent breast cancer by modifying the risk factors that we know we can. Let's talk more about that. Remember this slide? This lists our modifiable and our non-modifiable risk factors. Now there's very little that you can do about being born as a woman or getting older, a little that you can do about your genetics that you were born with, and little that you can do about benign breast diseases that you happen to have as part of your general makeup. Your endogenous hormones, that is to say the hormones that your body makes, well I've got a question mark beside that, and we'll talk more about how we can potentially modify the effect of those hormones. On the modifiable side however, there's a lot that we can do. So, we know that exogenous hormones, hormone replacement therapy for example, makes a big difference in terms of your breast cancer risk. And we noticed that when women got word of the fact that taking hormone replacement therapy increased their breast cancer risk and stopped taking hormone replacement therapy, we saw nationwide a reduction of breast cancer incidents. What about breastfeeding? We know that breastfeeding actually reduces your risk of developing breast cancer. Alcohol, so moderate intake of alcohol is okay, but excess intake can certainly increase your risk. So you want to limit the amount of alcohol you take in. And obesity, later on we'll be talking about survivorship issues, and one of the big issues is maintaining an ideal body weight. So certainly those are things that we can do something about. High dose radiation, well that's an exogenous factor. It's sometimes modifiable, in the sense that we can avoid getting radiation to our chest, but sometimes it's non-modifiable. Like, if you just so happen to be near Chernobyl at the time of the big disaster, it was little that you could do about it. So let's talk a little bit more about what we can do in terms of reducing our risk. I hope that all of you took the opportunity the last time to actually go to the web site that I showed you, where you can quantify your five year risk. What was that? Was it more than 1.67? If it was, you would be what we would term as,at high risk. That isn't to say that there's nothing you can do about that, there is. There's a lot that you can do. And there are a number of risk reducing strategies. Each of these strategies, however, has advantages and disadvantages, and reduce your risk by varying quantities. So the first risk reducing strategy is frequent surveillance. Now, frequent surveillance doesn't really reduce your risk, although it does reduce your risk of dying. Here, the whole strategy is behind finding cancer early, so that we can detect it at an early stage when treatment is most effective. We'll talk more about frequent surveillance. So, the risk reduction in terms of finding cancer, and developing cancer is zero, but it does have a big risk reduction in terms of dying of the disease. What's the next category? Chemoprevention and, or prophylactic oophorectomy. I lump those two together because they work essentially by the same mechanism. Chemoprevention is not chemotherapy. It really is endocrine therapy, that is to say, blocking our natural hormones. That's the same thing that a prophylactic oophorectomy would do. So if you're pre-menopausal and you take out the main source of estrogen, your ovaries, you're reducing your natural hormones. Remember endogenous hormones? That's a modifiable or non-modifiable, question mark, risk factor. By reducing endogenous hormones, we can reduce our risk of developing breast cancer by 50%. So we'll talk more about some of the strategies there, and some of the agents that we can use that'll reduce risk. Now, what is the most effective way to reduce your risk of developing breast cancer? Well, remove both breasts, if you don't have any breasts you should maximally reduce your risk of developing breast cancer. You'll notice however, that prophylactic mastectomy is not associated with a 100% risk reduction. Now, some of you may be scratching your head and thinking, if I don't have any breasts, how could I possibly get breast cancer? Well, the answer is, no matter how good a surgeon you have, its impossible to remove every single solitary cell. So the risk reduction is about 95%, not a 100%, but still pretty good, and we'll talk more about what that operation in entails. But let's go back and talk about frequent surveillance. What is frequent surveillance? What are the modalities that we use? Well, some of these are pretty common place, things like, self breast exam. Self breast exam is something that we often use just in the general public, to raise breast cancer awareness. Now the data are mixed as to whether this can actually help you to find a cancer early, and whether in fact we save more lives with self breast exam. But there's no doubt about it, if you get familiar with your own body, you can clearly identify when something abnormal is going on, and seek treatment earlier. Clinical breast exam, that is to say, having a clinician, a doctor, a nurse practitioner, your OBGYN, your family practitioner, do a clinical breast exam is another layer of prevention. So here your doctor would do a breast exam, making sure that they don't feel any lumps or bumps, that they don't see any skin changes or nipple discharge. They feel in your lymph nodes to make sure that they don't feel any swollen lymph nodes. And again, this is yet another layer to try to find breast cancer early. The mainstay, however, is mammography. When we talk about imaging, this really is the mainstay of therapy. We know that with mammograms, we can find cancer early, and there are a number of clinical trials that have demonstrated that mammograms save lives. There's a lot of debate about when you should start mammograms, when you should stop, how frequently you should have them. We'll talk more about that when we talk about mammography in the imaging section. But suffice it to say, that mammograms really do make a difference in terms of surveillance. And mammograms in general should be had once a year. So what about MRI? Now MRI is more controversial. There are, however, data that MRIs should be something we consider in high risk populations once a year. So who is high risk enough to get an MRI once a year as part of screening? Well, these are patients who have a BRCA 1 or 2 gene mutation. Remember these people are at extremely high risk of developing breast cancer, 80 to 85% lifetime risk. And so, using a very sensitive modality like MRI can really be helpful in this population. Who else? People who have a family history of a BRCA 1 or 2 gene mutation, who haven't been tested themselves. Or, people who have a 20 to 25% lifetime risk by BRCAPRO, or a similar model. Now, remember the model that you did the last time we met? Well that what we call the Gail model. It doesn't really encompass a lot of family history. The questionnaire really only asked you about your first degree relatives. So it's important to realize that what we're talking about here is really a family history derived genetic risk model. Okay, so, that's frequent surveillance. It really doesn't reduce your risk of developing breast cancer, but can help you to find breast cancers early. What about chemoprevention? So as we talked about chemoprevention is not chemotherapy. This is using what we call either selective estrogen receptor antagonist, or aromatase inhibitors, which also reduce the effect of our naturally circulating estrogen in producing breast cancers. So by taking this agents, we can actually reduce the risk of developing breast cancer by about 50%. Selective estrogen receptor modulators, or what are fondly known as as SERMs, include things like Tamoxifen and Raloxifene. Raloxifene is something that we should only really be considering in post menopausal women. Both of these agents act at the receptor of the estrogen receptor. So, they work in a different way than the aromatase inhibitors. Now, the aromatase inhibitors are also only for post menopausal women, and they act by inhibiting aromatase, as the name implies. This is the enzyme that converts circulating steroids in peripheral fat that are made by your adrenal glands into estrogen. Let's take a look at a schematic. So your adrenal gland makes steroids, and aromatase helps to convert those steroids into estrogen in peripheral fat. Your ovaries, in premenopausal women, make estrogen de novo. The estrogen that's circulating around acts on its receptor. And that receptor, as we talked about and will continue to talk about, is something that we see in breast cancer cells. So by blocking estrogen, we can really treat breast cancers as well. We'll talk about that when we talk about endocrine therapy in the medical oncology section. So SERMs act at the receptor. It doesn't really matter where you got your estrogen from. So an agent like Tamoxifen will block estrogen that was produced from the ovary, it will also block estrogen that was converted in peripheral fat. Drugs like the aromatase inhibitors, and their are number of them, Anastrozole, Letrozole, Exemestane, all cousins of each other but, all in same group of drugs, block the conversion of steroids made in the adrenal glands into estrogen, the end result is the same. We're reducing estrogen that's circulating around in the system, and that reduces our risk of developing breast cancer. Here are some trials that have demonstrated the risk reduction with all of these agents. You can see that many of them have been done with Tamoxifen, and the risk reduction is about 50%. The largest study was the NSABP P-1 trial with over 13,000 women and a follow up of 7 years, we see that the relative risk, that is to say, how much did your risk actually reduce using Tamoxifen versus placebo, was a dramatic reduction, a relative risk of 57. The other studies, similarly, found risk reduction. Raloxifene, when compared to Tamoxifen, was about the same. Exemestane is one of the aromatase inhibitors, which, in the MAP3 trial, also found a risk reduction. This is a lot of data, and I'll leave you to look at this on your own. Suffice it to say that these drugs work. So what's the downside? because there's always a downside. The downside is side effects. And as always, it's important to think of the eligibility criteria for each of these trials. All of these trials looked at women who were at high risk by Gail model. So that's the model that you used. If you were over 1.67 on a 5 year risk, you'd be eligible for this. Or if you had a history of LCIS, lobular carcinoma in situ a marker of increased risk. But, all of these studies looked only at women over the age of 35. Now, certainly the studies with Tamoxifen used pre-menopausal women. Raloxifene and Exemestane, only postmenopausal women. And you can see that the side effect profile for each of these drugs is different. So, Tamoxifen has a higher risk of clots, DVT's, or pulmonary emboli, which are blood clots either in the lungs or in the legs. A higher risk of endometrial cancer and cataracts, fracture not so much. Actually, as a selective estrogen respecter modulator, Tomoxifen actually has estrogen like effects in bone. And Raloxifene actually reduces your rate of fractures. It was originally invented as a drug for osteoporosis, that was then found to also reduce breast cancer risk. Now, Raloxifene also increases the risk of clots, which is eliminated with Exemestane, but then again Exemestane is only for postmenopausal women. So when thinking about risk reducing strategies with chemo prevention, there's a lot of things to consider. What about prophylactic oopherrectomy, removing the ovaries? Well again, this reduces your risk of breast cancer by 50%. It's a surgery, but the other advantage to prophylactic oopherectomy is that you can reduce your risk of ovarian cancer by up to 80%. When we think about genes that could predispose you to breast cancer, things like the BRCA 1 and 2 gene mutations, well, they increase your risk not only of breast cancer, but also ovarian cancer. So, particularly for patients who are BRCA 1 or 2 gene mutation carriers, an option like prophylactic oopherectomy can reduce their risk of developing breast cancer and their risk of developing ovarian cancer, it's kind of a twofer. So for many women like that, this is a very good option. But the way to reduce your risk maximally of developing breast cancer, as we mentioned, is a prophylactic mastectomy. This reduces your risk of developing breast cancer by about 95%. And you'll remember, I show you here Angelina Jolie on the cover of Time, this is something that many celebrities have really popularized, particularly when they were at genetic risk. Now, while this seems like a drastic maneuver, certainly it is a big operation, it's something that has become more and more acceptable with newer surgical techniques, advances in reconstruction. It really is something that can reduce your risk of developing breast cancer, while still giving you a wonderful cosmetic result. We'll talk more about this when we talk about surgery and plastic surgery, but suffice it to say, that this no longer is something that many women are thinking as a last resort. For many women, it's something that they really are considering. Especially if they are at high risk. So we've covered kind of the gamete now of prevention. Thank you so much for joining me. I hope you'll stay tuned as we learn more about breast cancer next time. Until then, this is Dr. Anees Chagpar.
