Genetic Counseling, Cancer Screening, and Risk Reduction

How I Practice Video Series 
Dr. Susan Modesitt, MD, FACOG, FACS

Genetic Counseling, Cancer Screening, and Risk Reduction from ACOG on Vimeo.


Transcript: Genetic Counseling, Cancer Screening, and Risk Reduction

Most cancer is actually not due to an inherited genetic defect, but about ten to twenty percent is, and it’s really important to identify those patients as coming from a high-risk family so that we can intervene and implement screening and risk reduction strategies to hopefully prevent them ever developing cancer. So, when a patient first comes in to evaluate their risk, I start off with taking a full three-generation pedigree, if at all possible, and it’s important to really ask patients both about their siblings, their parents, their grandparents, and aunts and uncles, as well as about specific cancers. So, for example, I will ask about breast cancer and if someone has a breast cancer patient in the family, and I’ll ask about what age, because genetic cancers tend to be earlier in onset, and so, if I’m thinking about hereditary breast and ovarian cancer, I ask about breast cancer, I ask about ovarian cancer, and then it’s also important to ask about some of the other lesser known cancers than may go along with hereditary breast and ovarian cancer, particularly pancreatic cancer, prostate cancer, and even melanoma. If I have a family I’m worried about Lynch syndrome, then I will ask particularly about endometrial cancer, uterine cancer, kind of both together, patients may not know which one is going on, ovarian cancer, colon cancer, as well as pancreatic cancer, small bowel, gastric, and brain cancer. Some lesser known syndromes that sometimes come up would be Cowden syndrome, the hallmark of which would be uterine cancer, breast cancer, as well as thyroid cancer. Another thing you can do if you’re thinking about Cowden syndrome is also measure the patient’s head circumference. In women, macrocephaly is fifty-eight centimeters or more and that is the hallmark of Cowden syndrome as well. So once I’ve done that, and have a patient that I’m concerned may have a hereditary defect, the next thing I will do is actually use some models to try and quantify both their risk for carrying a mutation as well as some of their risks for developing the cancer. So, if it’s a hereditary breast and ovarian cancer family that I’m worried about I will start of using what’s called the Tyrer-Cuzick model. This is a freely available model that was developed by two gentlemen in the United Kingdom. What it does is it takes the patient’s personal risk factors, including age at menarche, menopause, how many children they had, how old they were with their first child, history of breast biopsies or anything like that, as well as the family history of both breast and ovarian cancer. It will generate a pedigree, it will generate what their lifetime risk of developing breast cancer is, which then can inform you on whether or not they need to have breast MRI added into the mammogram, and then lastly it will give what their predicted risk of carrying a BRCA mutation is, and if it’s high enough it may merit referral for genetic testing and counseling. If it’s a family where I’m worried about Lynch syndrome, there’s a separate model called the PREM 126, also developed by a university, also available freely online, and what you do in that situation is you input all of the first and second degree relatives of the family with Lynch-related cancers, and at the end it will generate what that patient’s risk is of carrying one of the three main mutations for Lynch syndrome, which are MSH2, MSH6, and MLH1. So, once I have those two things in hand, or if it’s just a family where there’s just a lot more cancer than you would expect, multiple generations effected, young age of diagnosis, but it doesn’t really classically look like one of the syndromes, regardless, I will refer them for genetic counseling and testing. Unless you’re going to make this a niche of yours, I really recommend having to go to a cancer genetics professional that you’re going to send these patients to, because often it’s not the patient in front of you that needs the genetic testing, but rather a cancer-affected relative, because when we start the testing we would like to test the patient with cancer, because if they have a defect, then that’s why they got cancer, and then we can very quickly evaluate everyone else in the family who’s blood-related and either clear them of risk as a true negative and just go on with regular cancer screening or a true positive in which case we do need to institute a more rigid screening and risk reduction measures. So, again, I would really probably recommend most folks refer out to have this done, because everything changes constantly. Now, once we’ve identified a high-risk patient, the next step is really to implement different screening and risk reduction strategies. So, talking about screening first, with regard to breast cancer, remember, the Tyrer-Cuzick model will give you a lifetime estimated risk of developing breast cancer. If that risk is twenty to twenty-five percent, or the patient harbors one of the mutations that put them at higher risk for breast cancer, we’re going to add in to the mammogram a breast MRI, so they will get the mammogram once a year in January, they will get the MRI once a year in July, and get one or the other test every six months with the hope of picking up a cancer early before it has metastasized and where it is readily curable. With regard to ovarian cancer, most of you know ovarian cancer screening, as it is now, is not very efficacious. It does not pick up early cancers, it has a lot of false positives, and we do a lot of unnecessary surgery, so with my patients who are high enough risk to merit ovarian cancer screening or risk reduction I actually focus on risk reduction and risk reduction surgery. I will do screening up until the time I’m going to operate on them, but I make sure that they understand, I cannot promise we’re going to pick up a cancer early, nor if I pick up a cancer it’s going to be curable, so we really focus on risk reduction measures. With regard to endometrial cancer, most women will present early with abnormal bleeding, so I recommend prompt evaluation of bleeding, rather than endometrial biopsies or ultrasounds, and ultrasounds aren’t really effective for looking at the endometrial stripe, because most of these women are going to be premenopausal, so you can’t rule out cancer based on that. Don’t forget about colon cancer screening, it’s really important that women coming from Lynch families get their colon cancer screening and they get it early enough to detect it. We do want to start any screening, in any of these high-risk families, at least five to ten years before the earliest cancer diagnosis in the family. Again, once we’ve identified the high-risk patients, we’d really rather prevent cancer than to pick it up early or try and cure it, and so the big focus is on what drugs or surgeries can we do to reduce the risk of cancer. So, starting with the drugs, for breast cancer risk reduction and chemo prevention, there are two drugs, tamoxifen and raloxifene. These are drugs that are anti-estrogens in the breast, and high-risk women, if they take them for at least five years, it reduces the risk of cancer in half. Okay, so these are drugs that we should be talking about with our high-risk patients, about the pros and the cons and whether that is something that they may be interested in doing. With regard to ovarian cancer and uterine cancer risk reduction, it’s something that we already know and love, birth control pills. These are the greatest thing since sliced bread as far as I’m concerned. What they do is if you take them for at least five years they reduce the risk of ovarian cancer and uterine cancer in half. So these are something that can be offered both to high-risk patients and normal-risk patients in terms of reducing the burden of cancer on our entire population. The other methods, the transdermal or the vaginal hormonal contraceptives, may work as well, we just don’t have as much data on them. Another drug that is coming around is aspirin. Full dose aspirin in Lynch cancer patients seemed to reduce the risk of colon cancer in half, and there also may be some benefit in reduction of breast cancer risk as well. And then lastly, surgery. Surgery is really something I reserve for women that have been diagnosed with a known deleterious genetic mutation that puts them at higher risk, or their family history is so horrific but we have not identified a mutation and we want to investigate surgery options. So, looking at the breast first, we can do a risk-reducing mastectomy, this can be nipple-sparing or total mastectomy. They seem to be equivalent, and that will take, for example, a BRCA mutation carrier from an eighty-five percent lifetime risk of breast cancer down to under five percent, so it’s something that really needs to be talked about with these patients. With regard to ovarian cancer risk reduction, taking out the tubes and ovaries will take the risk in a BRCA carrier from a twenty to forty percent risk down to a one percent risk. A lot of discussion has now centered around, “Can we just get away with taking the tubes out first?” We do think the tubes are absolutely involved in ovarian cancer, and that it may originate there, so for some patients taking the tubes out, whether they’re high-risk or not, their having surgery is something to consider. The jury is still out whether we can get away with just taking the tubes out and leaving the ovaries in, but there are a bunch of ongoing trials, and I hope that question will be answered in the next five to ten years. For Lynch syndrome, uterine cancer, we definitely do want to take the uterus out, and would recommend taking that out after childbearing is complete. For any of these risk reducing surgeries, we do want to do the surgery, kind of like the screening, at least five to ten years before the earliest onset of cancer in the family, and so for BRCA1 carriers we tend to like to do the surgeries, the BSO, somewhere between thirty-five and forty. For the rest of the mutations, we may be able to wait as long as forty to forty-five, but again, we would tailor any intervention about the time the earliest cancer was in the family. So, that sums up genetic counselling, screening, and risk reduction, and that’s how I practice.

When I talk to patients about prenatal genetic testing, I always start the conversation by reminding them that most babies are born healthy and without any kinds of birth defects. There’ve been so many advances in genetics recently that we talk to patients about all kinds of testing for all kinds of disorders, and it’s important that they not be alarmed by that, so I do always remind them that the vast majority of babies will be born healthy and that the fact that I’m offering these tests does not mean that they are at high risk. I think it’s also, then, next, important to explain that some patients want to have testing for birth defects and want as much information as they can get about the possibility there could be a problem, where other women choose not to have any kind of testing at all, which is completely and totally fine and is their choice, whether they want to have any testing done. For women who do want to have testing and they have more questions, there’s two choices: one is they may choose to have a diagnostic test, which gives the most information and is the most accurate, but does involve an invasive procedure like an amnio or a CVS, but I do mention that this is an option for any pregnant woman and offer it to all of them. For the majority of women, though, they are happy to have, and prefer to have, a screening test to give them more information about whether they are at higher risk than average and whether they might want to go on and go down that diagnostic test pathway. So, for most women, they are interested in screening tests, and I’ll explain to them the different screening options, and I think it’s helpful to have a pathway that you offer to all patients, which in our practice is the serum analyte screening and ultrasound screening that provides risk for a broad array of pregnancy complications as well as birth defects. So, we offer those tests to our patients and determine, based on those tests, what their risk level is. I think that, although prenatal genetic testing is certainly complicated, it is a pretty straightforward conversation that I distill down into a couple of easy questions: “Do you want to have any kind of testing?”, and “If you want to have testing, do you want to have a diagnostic test that gives you the most information, the most accuracy, but involves an invasive procedure, or do you want to go start with a screening test or starter test to get a better sense of your risk level?” Those two simple questions can usually get to what’s the best option for your patient, and that is how I practice.

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