Implementing a Risk Assessment/Genetics Program

Need for Genetic Counseling

The need for genetic counseling, a nice article by hall some years back, estimated approximately 1.4 million United States women have been a family history of breast cancer that based on criteria established by the US Preventive Services task force, would permit referral for genetic counseling and potentially, genetic testing.

So 1.4 million US women, but however, fewer than 2% of these women, that are candidates for genetic counseling report having been tested.

So there's still quite a bit of, a lack of understanding of risk and what to do if you may be considered at risk.

This is what our talk is gonna be about today.

BRCA Prevalence

The BRCA prevalence overall disease related mutations in BRCA one and brca DO genes have been estimated as one in 301 in 800 respectively.

So for those patients that BRCA one or BRCA two.

Implementing a Genetic Counseling Program

The initial step, if you're thinking about implementation of some type of genetic counseling or risk assessment program, do you have to determine the need at your facility or department?

The number of high risk MRIs that we were doing at Elizabeth, Wendy Breast care steadily increased over the last several years.

Our physicians found themselves spending a larger amount of time counseling patients regarding their risk of breast cancer.

The patients were increasingly initiating discussion during visits to our facility.

So we thought that there was a need in our community for genetic counseling and testing and being a comprehensive breast center.

We felt it was an important service to provide to our patients.

The initial program started with one of our medical assistants and our MRI nurse running the program.

Genetic testing will be performed based on patient's risk factors and also primary care doctor recommendation.

That's how we started. That didn't get us very far because our MRI nurse was busy doing other things and it was hard to, give that program her full attention and she was not extremely qualified for that.

So we ended up hiring a certified genetic counselor, beginning in 2011.

And she started at three days a week because we didn't really know how much need there would be for a full-time genetic counselor.

She increased to four days a week by September of the same year because of high patient demand.

So within several months she went from three days to four days.

Current Workflow

Currently our workflow is such as this.

The patient will check in at the reception desk.

Her family history and demographics will be entered by our reception staff into a dashboard.

It's a computerized system that was developed by us at our facility and a programmer that is a consultant for us.

The patients have a history sheet, regarding information about their health and their family history and other concerns, medications that they fill out.

They can bring it with them, they can download it from online that we mail it to them in the mailings that they get from us.

So they bring it usually filled out.

A small number of patients sit out in the front waiting room, filling it out, and then our staff will enter it.

Patients are flagged by this program that we've created.

If the responses on the health history form meet specified, national Comprehensive Cancer Network guidelines.

High Risk Flagging Criteria

So what is a high risk flagging?

It's based on two points according to the NCCN guidelines.

If you have a personal history of breast or ovarian cancer, at 50 or under each occurrence will be two points.

If you have a personal family history of breast or ovarian age 50 and over each occurrence is one point personal or family history of breast or ovarian age 50 and under each occurrence two points.

So it's really based on your family history, personal history, and your age, whether it's a one point each occurrence or two points.

If you're a Ashkenazi Jewish ancestry, one point if you have a family member with a known genetic mutation, that's two points such as BRCA one or two.

Factors for Identifying Women at Risk

So the factors for identifying women at risk for breast cancer, you wanna identify the high risk women in your practice based on their family history and its early onset.

So the NCCN guidelines say age 50, but insurance carriers pretty much consistently now are saying for the family history, 45 or less.

So genetic testing has a patient tested positive, has a family member first, second or third degree relative.

If that's the case, if you have a family member that's been tested already and they're positive, then your patient can have site specific testing instead of the comprehensive panel and that is much less expensive than the comprehensive panel testing exam.

If there's a clinical history for atypical lesions such as A-D-H-A-L-H-L-C-I-S radial scar, then by utilizing the entire acoustic risk assessment model, then that patient may also qualify for breast MRI.

So family history is the main determinant of risk, especially at a young age.

The risk can be transmitted by either men or women.

The probability that a child will inherit the parent's susceptibility 50%.

It's a nice article by Robson and it was in the New England Journal of Medicine in 2007.

It's a nice review article about risk.

So for women who are not of Ashkenazi Jewish descent, one first degree relative under the age of 45 will get you there to start thinking about genetic testing.

If you have two first degree relatives, mother, daughter, or sister diagnosed with breast cancer, one of whom was diagnosed at 50 or younger, that also will get you there three or more, first degree or second degree relatives, grandmother or aunt diagnosed with breast cancer regardless of age.

So as you're getting into the second degree relatives, then you need more of those relatives.

Three to start thinking about genetic testing.

Combination of any relatives diagnosed with breast cancer and ovarian cancer.

One cancer type of person, a first degree relative with cancer diagnosed in both breasts, that's a first degree relative, mother or sister, any relative diagnosed with ovarian cancer regardless of age.

So ovarian cancer gets you there and any relative diagnosed with both breasts and ovarian cancer, regardless of age and breast cancer diagnosed in a male relative,

Education and Resistance

we found it imperative to educate our staff and our referring physicians.

We're still experiencing some resistance from referring doctors.

Education is greatly helping with that.

So we educate our physicians, we have written articles and our genetic counselor also has written publications in local papers and local women's magazines to get the word out.

Cancer risk assessment and genetic counseling pamphlets are developed internally and we make that available to our patients and their families and we also mail 'em to the doctor's offices.

Approximately 17% of our patient population is flagged as high as high risk.

I have to say that we have a relatively skewed population.

The women that we diagnosed with breast cancer continue coming to us and they send their family members.

And so we seem to have a lot of young women that are high risk that come to our facility and their families.

Patient Notification and High Risk Process

So once the screening patient has their screening mammogram and their results are normal, if they are considered high risk because they got those points, they were flagged by the computer system, we created.

A high risk letter is printed and given to the patient.

A similar letter is sent to her referring doctor.

This high risk letter explains why she was flagged as a possible risk.

So the patient will not leave our facility not knowing what's going on.

It will say something, dear Mrs. Smith, because of your personal history of breast and or ovarian or your mother's history of breast or ovarian or cause an aunt, the way she filled out her information sheet so she knows the patients are notified of their risk factors and then they can call and undergo a phone assessment.

This was initially performed by the genetic counselor, the phone assessment.

However, because of the large volume of phone calls, we now have a medical assistant that has been trained to answer the those calls.

The screening is deter is to determine if the patient is eligible to continue on to genetic counseling or testing.

And predominantly that's for insurance purposes 'cause it's an expensive exam.

So a patient is known to be eligible if they meet any of the below breast cancer, less than 45 years old with breast cancer, two relatives under 50 years old with breast cancer or three relatives at any age with breast cancer.

That pretty much gets you in or ovarian cancer, any relative regardless of age.

So when a patient is determined to be eligible, the appointment by the assistant that answers the call, then an appointment is scheduled with a certified genetic counselor.

Genetic Counseling Appointment

During that appointment, an in depth interview is conducted.

The information collected is personal history affected or unaffected if the patient is affected or unaffected age, amen.

Key menopausal status hormone use, prior breast biopsies and any additional relevant personal history.

So family history, any cancer history, not just breast or ovarian.

If there are Ashkenazi Jewish descent risk assessment is then performed.

And you wanna determine the lifetime risk for the patient for breast cancer.

Does the patient meet the NCCN guidelines or the American Cancer Society guidelines?

Does the patient fulfill her insurance guidelines, which may be a little different and more strict?

So a plan of action is formed.

Is the patient eligible to continue to genetic testing?

Does the patient not qualify for testing but does she qualify for a high risk MRI?

So we use a computerized risk assessment model to determine patient risk percentage for BRCA one and BRCA two genes and lifetime cancer risk for breast cancer.

So entire acoustic assessment or the Gale or BRCA PRO may be used for entire acoustic is not all inclusive for the particular patient.

If a patient has any male family history, you cannot use the TY acoustic model.

The cancers that may be associated with a BRCA mutation are obviously breast, ovarian, prostate, melanoma, pancreatic and kidney.

The risk assessment models that you will be using for risk of developing cancer over a time span.

Obviously the gale model Klaus, we use the tire acoustic as much as we can because it's more inclusive or BRCA pro.

The gale model usually will minimize the risk and you'll get a percentage as close to 20% but not quite.

Now if you wanna know about your probability of a BRCA mutation, you may wanna use the myriad tooth, the Cusic BRCA Pro, there's Frank Etal and Manchester.

Genetic Test Results

So what are the results? What are you gonna get?

Well the patient has a genetic testing.

Let's say they're positive, they carry the mutation, they're negative.

If there is no known BRCA positive family member, the possibility remains that even if they're negative, there's an undetected mutation, something we haven't found yet.

Or there may be a true negative.

When there is a known BRCA positive family member and you the patient has a negative result, that means her risk is as a general population or you have an uncertain result.

It's a nonsense mutation of unknown significance.

And we have gotten some of those.

So our genetic counselor averages approximately 19 to 31 appointments a week.

That's a face-to-face visit with a patient that's already been determined, determined to qualify to move on with genetic testing or a risk assessment.

So we do the counseling and testing.

The blood draw can happen on the same day, but usually we have to get insurance pre-authorization for most insurances.

So the blood draw will happen on a different day.

The results usually are available in three to four weeks.

So, so far after December of 2013, remember I told you we started with a program early in 2011.

So we've done 1063 tests that have been ordered.

44 were positive, 20 were BRCA 1 21, BRCA two, two lynch syndromes one, check two and 749 were negative and 22 were that variant of unknown significance.

Lynch Syndrome

So what about the Lynch syndrome?

I mentioned we found some of those.

Well that can be MLH one, MSH two, MSH six, MPMs two.

Those patients are at increased risk for colon cancer and cancers of the endometrium, ovary, stomach, small intestine, hepatobiliary tract, urinary tract brain and skin.

52 to 82% lifetime risk for colorectal cancer cancer.

And the mean age could be 44 to 61 25 to 60% of endometrial cancer in women with a mean age of 48 to 62, 6% to 13% for gastric cancer and four to 12% for ovarian cancer with lynch syndrome.

Mean diagnosis for ovarian cancer may be 42 and a half years old.

Approximately 30% of women may be diagnosed with ovarian cancer, less than 40.

So for the Lynch syndrome there is all these other associated cancers that they're at high risk for when you do identify that.

So your genetic counselor will not just be doing testing for Baca one or two, but they're checking for other things that are very relevant to this patient and this patient.

There's a relationship with ovarian cancer and Lynch syndrome.

The relationship between breast cancer and Lynch syndrome is unresolved.

And there they're not studies out there that say consistently the lynch syndrome leads to a higher breast cancer risk check two or checkpoint kinase two is a leap from ME syndrome and that's associated with development for some classic tumors.

The soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, brain tumors, adrenal cortical carcinoma and leukemias diagnosis of breast cancer before age 30.

If you have a patient that you diagnosed before 30 and they don't have a BRCA mutation, you, there's an estimation of four to 8% likelihood of having this mutation that leave from any TP 53 breast cancer diagnosed between 30 and 39 also has a higher risk of having that mutation for the lead from Manny syndrome.

Women with LFS are a greatly increased risk of developing premenopausal breast cancer.

So a cumulative lifetime risk of breast cancer is 28 to 37%.

So, so far we discussed the Lynch syndrome that isn't association with ovarian cancer for women that are young.

And here we have an association with Lee Fromen syndrome and women with premenopausal breast cancer.

Johnson in 2005 wrote a nice article looking at 5 569 bilateral breast cancers that had the wild type for check two.

And what they found was that these patients, the relatives at three times the population risk of female breast cancer, twice the risk for prostate and a large axis of male breast cancer relatives of those who were carriers of check two, this deletion is the 1 1 0 0 deletion C had an even higher risk of breast cancer and prostate cancer.

The results were interpreted as indicated, a multiplicative interaction.

So between check two and this additional deletion and other unknown susceptibility genes.

So the author suggests that if you have a bilateral breast cancer case and their families, those patients and their families are likely to provide an efficient basis for identification of additional low penetrance breast cancer genes.

So we're not just dealing with BRCA one and BRCA two, there's other genes that are working and they may have an additive effect.

And so you have to think about those and your genetic counsel will guide you into what to do with these patients that are high risk for breast and ovarian cancer.

Variants of Unknown Significance

This is the variant of our known uncertain significance.

That's a result you may get.

I hate that result because the contribution of this variant to relative risk for breast and ovarian cancer is not established at this time and there's not enough individuals that have this to know what to do because we don't know the significance of this result.

We follow the NCCN guidelines to manage the patient until more information is out about the significance of this.

So if we have an inconclusive result, the family studies can be performed.

So we have the patient, you know, get parents affected, relatives to come in and the lab will check the family members and amend the report as more data comes in.

And we work with myriad and other labs and they offer free of charge testing for the family members.

So when you have this uncertain significance result, they will test the family members, to see what's going on with that and they won't charge the the family members.

Initially patients were brought back for further discussion with a counselor if their result came back positive or if it was this unknown variable result or if there was a possibility for further testing after a negative result.

But as of February of last year, so we've been doing this for a year, all the patients are brought back.

The results are discussed face-to-face as well as the implications for the patient's family and recommendations for medical management.

We found that over the phone, giving the patient the results was very difficult and the patient was left with many questions and then the family members had questions.

So now we sort of invite the family members to come in and hear it with the patient and and have a face-to-face meeting with a genetic counselor.

BRCA Gene Mutations and Risks

Mutations in BRCA genes, clusters in families exhibiting an auto autosomal dominant pattern of transmission can account for five to 10% of cases of breast cancer overall.

Some nice articles here that I have included for you to look at.

So for breast and ovarian cancer risk for the BRCA one and BRCA two carriers, which is the ones we know most about the carriers by age 70.

For the breast, 87% risk, that's a very high risk for breast cancer over the patient's lifetime carriers by age seven for ovarian 44% risk.

So if you are BRCA one positive, you have a breast cancer risk of 87% by age 70 for ovarian cancer, 44%.

You're also at risk for developing a second primary breast cancer.

20% within five years of initial cancer diagnosis and 64% lifetime risk and a subsequent ovarian cancer tenfold increase for male breast cancer, 8% lifetime risk and a small increase risk for other cancers, which we mentioned before, prostate, pancreatic, and melanoma.

For BRCA two, the breast cancer risk is 84%, so almost as high and for ovarian cancer, 27% by age 70 for a second.

Primary breast cancer, 12% within five years of initial cancer diagnosis, 64% lifetime risk for a second primary cancer, a subsequent ovarian cancer, 16% lifetime risk, male breast cancer, 8% lifetime risk and a small increased risk for the other cancers.

The same ones, prostate, pancreatic and melanoma.

This is an article by Ford and he looked at 237 families with at least four cases of breast cancer estimated BRCA one linked disease in 52% of the families estimated BRCA two linked disease in 32% of the families neither gene linked in 16%.

So majority of families with male and female breast cancer were due to BRCA two 76%.

So if you see male and female think BRCA two, the impact of risk information on patient management is unclear.

Even with a negative genetic result, patient may be eligible for MRI screening the American Cancer Society recommends annual breast MRI for women that have a greater than 20% lifetime risk.

Most experts suggest aggressive surveillance mammography, physical exam and MRI at six month intervals.

This is what we recommend commonly beginning somewhere between 25 and 35.

So approximately 464 patients from our genetic program have been referred to high risk MRI since May of 2011.

So this is through November, 2013.

So now we're talking about two and a half years.

52 biopsies were done in this group of 464 patients that were eligible for high risk MRI from our genetic program.

14 cancers were diagnosed, so it was 3% from the 464 patients referred and 26.9% positive biopsy rate 14 outta 52.

Case Examples

Case 1: 53-Year-Old Unaffected Patient

I'm gonna go some over some examples with you.

53-year-old unaffected patient.

So she's fine with a history of breast SIS and dense tissue.

She has a family history that she reports on her health history form of, of mother at 67 with breast cancer.

Maternal grandmother at 68 with breast cancer, maternal grade and breast cancer at 80.

So of course she has three members.

Remember we said who gets flagged by our, our, our program.

Well she has three so she's flagged.

She gets a high risk letter.

This is her mammogram in July of 2011.

That was read as negative by us.

And so she has a risk assessment.

Her family history because she has three family members do fulfill the NCCN guidelines, however, for BRCA testing, but they do not meet her insurance carriers guidelines and we find that frequently for coverage, the exam is expensive.

The patient refuses to have the genetic testing and I don't blame her.

So, but we use the tire acoustic risk assessment model on her, she said 23.8% lifetime breast cancer risk.

So we plan to schedule her for an MRI.

So she's not eligible for BRCA testing because of her insurance, but we recommend an MRI and she decides to have it six months later after her mammogram.

So at a follow up, this is what we find six months later.

She has a small enhancing mass, which we were able to identify in her MRI.

This is a seven millimeter invasive cancer.

So now the patient is eligible for genetic testing 'cause now she herself has breast cancer along with the other family members And this will provide information on her risk of a second primary breast cancer and risk to her family.

This is the ultrasound of that patient.

So you remember how denser tissue was.

This is a small lesion and it was found on the high risk MRI.

This was an invasive duct carcinoma.

Case 2: 63-Year-Old Unaffected Patient

This is another case, a 63-year-old unaffected patient comes in.

She's had hormone use for 10 years and one prior benign biopsy.

She writes her family history as a sister with breast cancer at 68 maternal and with breast cancer at 80.

Maternal grandmother with breast cancer in her seventies sister with colon cancer at 62.

Two maternal uncles with colon cancer in their fifties and a son with papillary thyroid cancer at 41.

So it's a pretty comprehensive family history that the genetic counsel will collect.

So we do a risk assessment.

The gale model, she has 18% lifetime breast cancer risk.

Her five year breast cancer risk is 4.5%.

So she meets C-N-C-C-N guidelines for genetic testing because of this five year breast cancer risk.

So we plan then this is our plan of action, pursue genetic testing.

Her results reveal no deleterious mutation in BRCA one or two.

The patient declines any further testing for other syndromes.

We're worried about this patient.

She has all this colon cancer, all this other thyroid cancer in her son along with her the breast.

So we tested for BRCA one and two.

She does not wanna have any additional testing.

Remember we talked about the Lynch and li FRA many.

So she refuses the testing.

This is her prior screening mammogram. She has dense tissue.

It was normal. She does go for a high risk MRI and this high risk MRI reveals two lesions.

You see this kind of extensive background, enhancement pattern that she has.

And so this is the sagittal view and the 12 o'clock turns out to be benign.

The one o'clock turns out to be DCIS.

Both were biopsied under MRI.

Case 3: 51-Year-Old with Personal History

So this is another patient, 51-year-old diagnosed with breast cancer at 26 and thyroid cancer at 45.

So she has no family history on her health history form other than herself.

She was 26. Remember what we said.

Any family member including herself less than 45, gives you that high risk.

You get flagged. So she got flagged and so she schedules genetic counseling.

So during the genetic counseling, however, so patients don't always tell you everything in their history forms.

She has a mother with pancreatic cancer at 70.

She has a father deceased at 59 with metastatic breast cancer.

Primary unknown.

And although the patient did not report Eskenazi Jewish ancestry, her paternal grandmother was in a concentration camp.

So the genetic testing is done and she has a comprehensive BRCA analysis revealing a BRCA one mutation.

Remember 26 with breast cancer? You have to think of that.

So the patient's at increased risk for a second primary breast cancer.

So now she's eligible also for high risk MRI.

She's at increased risk for ovarian.

So she's recommended a bilateral soaping ectomy.

So the patient, the family has a 25-year-old daughter who comes in for genetic testing.

Now she tests negative for her mother's BRCA one mutation.

Remember now that's a true negative because we have a family member that's BRCA positive and now the patient's daughter gets tested.

She's negative. She's a true negative.

So the patient also has a sister, brother, nieces and nephew that may be at risk and eligible for genetic testing.

Case 4: 51-Year-Old with Family History

This is another patient, she's 51.

She reports on her health history form a sister with breast cancer at 55 that lives in Russia, maternal and with breast cancer at 49.

Deceased at 59. Maternal grandmother with ovarian cancer at 80.

So high risk letters generated 'cause she has multiple family members.

She schedules genetic counseling During this session we find out her mother was deceased at 86 with cancer of the nose.

Father deceased at 90 with throat or neck cancer.

She's non Eskenazi Jewish and a breast cancer risk assessment by the gale model 17%.

However, she qualifies for genetic testing and she's BRCA two positive.

So the patient now is at high risk for breast cancer.

So high risk MRI eligible.

She schedules, she's at increased risk for ovarian cancer.

So aggressive surgeries recommended the family.

Now there's a patient, the patient has a son, six unaffected sisters and a multitude of nieces and nephews who are at risk and eligible for genetic testing.

Case 5: 42-Year-Old Unaffected Patient

This is another case. 42-year-old unaffected healthy patient with a sister with breast cancer at 24, uterine cancer at 35.

Her sister tested positive for BRCA one.

She is a maternal aunt with breast cancer at 43 and 60.

That tested negative for brca.

Her maternal grandmother, cervical, or ovarian cancer at 41 had paternal first cousin with ovarian cancer at 55 and breast cancer at 72 she tested positive for BRCA uh mutation.

So you see this patient's very complicated.

She has some family members, maternal aunt that was ne negative, but a sister that was positive and a paternal first cousin that was positive.

So she has, you know, people in her family tree with a BRCA one mutation.

The risk assessment model done, the TYC shows she's at a 42.3% lifetime breast cancer risk and a 50% chance to carry previously identified BRCA mutation.

So she meets NCCN guidelines for genetic testing.

So the testing reveals she is positive for the BRCA one gene and she pursues a high risk MRI.

Screening this high risk MRI identifies this small enhanced in mass, which we were able to identify on ultrasound.

Targeted ultrasound is always very powerful.

Invasive duct carcinoma, nuclear grade two with DCIS.

And this was a young patient.

Impact of Genetic Counseling

So the data reviewed, this is a very nice article by Nelson.

It does a systematic review and update the US Preventative Services task Force recommendations for risk assessment.

So what they looked at is between 2004 and July, 2013, they found that genetic counseling actually increases the accuracy of risk perception, decreases intention for mutation, testing among unlikely carriers.

So people that are not really at risk by going through the genetic counseling, then you know you're not at risk and then you don't pursue unnecessary testing and decreases cancer related worry and anxiety and depression.

That's the impact of genetic counseling if it's done correctly.

Why is this important? By identifying patients with genetic mutations, we can review recommended medical management strategies for these patients, including breast, MRI, preventative surgery and or chemo prevention, and patients can discuss with their primary physician and establish a customized medical management plan.

Thank you.