Tag: Genetic Testing

BRCA alone or Expanded Breast Cancer Gene Panel

Breast Cancer

A Multigene breast cancer panel had a higher diagnostic yield than BRCA 1/2 Testing alone

A patient with a strong family history of breast and ovarian cancer wanted to know if there was any advantage to doing the broader panel vs. just BRCA 1/2.  Her family history was notable for breast cancer in her mother at age 52 and an aunt with ovarian cancer at age 47.  The family history was also notable for a maternal uncle with colon cancer and her maternal grandfather had Non-Hodgkins Lymphoma.  Unfortunately, her insurance had a very high deductible and she was going to pay out of pocket.  The BRCA 1/2 test alone can be done for $1500 but the multi-gene panels are much more expensive depending on the laboratory and the additional tests involved.

To answer this question we refer to a recent article published in the Annals of Surgical Oncology form July 2015. In the olden days prior to new methodology of next generation sequencing the strategy would always be to test sequentially.  In this case, that would be doing BRCA 1/2 first and if negative then move to the other genes that are less penetrant but confer an increased risk for breast/ovarian cancer.

In this study, they took patients that had undergone only BRCA 1/2 testing and then did further multi-gene panel testing.  The detection of BRCA 1/2 mutations were the same as would be expected because next-generation sequencing should also identify BRCA mutations.  However, approximately 4% of women were found to have non-BRCA mutations that were considered pathogenic or contributing to disease.  Most improtantly, almost 14% of women were identified to have Variants of Unknown Significance (VUS) in non-BRCA genes.

VUS usually require more interpretation in light of the family history but in cases where there is a strong family cancer history, many of them can be interpreted to be significant and contributing to breast / ovarian cancer risk and other cancer risk in that family and individual.

So what is our Testing Strategy:

  • BRCA 1/2 alone if the family history is significant for only breast cancer and/or ovarian cancer
  • Multi-gene panel if there is additional family history of non-breast / ovarian cancer.

If you have questions about testing strategy please call us at 352-235-9636 or toll-free at 855-474-8522

or

Schedule a Video Consultation

My PSA is high but I don’t have symptoms. Do I need a biopsy for possible prostate cancer?

PSA, PHI, Prosate Cancer

The Prostate Health Index (PHI) test and when it can be useful to diagnose prostate cancer

 

 

Our patient today had a PSA of 7.4.  He is a 67 year old Caucasion male with no other medical issues other than episodic high blood pressure.  He does report some mild urinary symptoms mostly involving going to the bathroom frequently but his urine stream is normal and he has no incontinence or dribbling.

He has had PSA testing in the past.  At one point it was 7.1 but after he saw a holistic practitioner it decreased to 4.5.  Approximately 6 months later it was 7 again and his primary care doctor thought it was worth evaluating further.  He did not want a biopsy and so had a prostate ultrasound performed and an examination by a Urologist.  His prostate was smooth and the ultrasound was benign so it was considered appropriate to just watch him.

The new PSA was 7.4 which does represent an increase from previous.  In addition, his urinary symptoms has worsened but not drastically so.  He still had a normal stream but had increased frequency in compared to before.

For a better risk assessment, we performed a Total and Free PSA.  Many physicians are not familiar with the Free PSA.

In men over 50 with an elevated Total PSA, the %Free PSA gives an estimate of the probability of prostate cancer

Our patient had a Total PSA = 7.4 and a %Free PSA – 22%. In this case, the ideal %Free PSA should be over 25%.  The lower the %Free PSA the greater the greater the probability of cancer.  Here is a table that shows the Estimated Probability of prostate cancer.

PSA(ng/mL)      Free PSA(%)     Estimated(x) Probability
                                     of Cancer(as%)
0-2.5              (*)               Approx. 1
2.6-4.0(1)         0-27(2)                   24(3)
4.1-10(4)          0-10                      56
                   11-15                     28
                   16-20                     20
                   21-25                     16
                   >or =26                   8
>10(+)             N/A                      >50


Given that our patient's Total was in the 7 range and the high Free PSA, the probability of cancer is low but still significant at 16%



Here is a nice graph from Quest: showing our possible decision tree.

 

This patient had a normal rectal examination so the liklihood of cancer based on the testing is still low but significant.  The next options are to refer for a biopsy, which he did not want, wait to re-test in 3-6 months to see how the numbers may change or to see if we can’t further risk stratify.

If we want to further risk stratify then we can consider using the Prostate Health Index (PHI).

This patient, like many, fall into that category that often result in a biopsy but don’t have cancer.  See our image above.  Of course, one never knows and that is why the biopsy is performed because who want to be the statistic that ends up with prostate cancer.

To help with this decision, researchers looked for an alternative biomarker which led to the discovery of the PHI.  PHI offers greater specificity in identifying patients that truly need a biopsy.

Phi is the only FDA approved blood test that is 3 X more specific than PSA alone.

The phi combines the use of another biomarker called p2PSA which is an isoform of free PSA that is the most prostate cancer specific biomarker found.  When p2PSA is used with the total PSA, and free PSA, the diagnostic accuracy improves to 71%

Phi-table-large

If you are like our patient who falls into this gray zone area and are concerned about getting a biopsy. Please call us at 352-235-9636 or Toll Free at 855-474-8522

or Schedule an Online Diagnostic Consultation

What is the Cost of EDS Testing?

Collagen, EDS
Collagen

What is the cost of EDS testing?

We answered this question for a patient without insurance the other day. We asked for client pay pricing at a number of large genetic testing companies that perform EDS testing. To clarify, EDS testing for which we obtained pricing was usually for panels that tested for multiple subtypes of EDS as well as Marfan and syndromes associated with vascular aneurysms. The reason for this is that with improvement in molecular diagnostic technology, we know that there is great variability between individuals and the old classifications based on pure clinical features is not as relevant.  The clinical features can hint at one type of EDS over another but the reality is that every individual has different manifestations based on their own private genetic alterations within the various proteins involved in collagen synthesis, assembly and degradation.  As a result, it is much better to do broad panel testing.

I have had numerous patients prove me wrong.  Based on clinical criteria, I have diagnosed Hypermobile type only to find out with testing that they had classic or another version of EDS.  The variability between individuals is what makes us unique.

So what is the cost of EDS testing?

$1500-$1750 not including medical consultation

High Risk Breast Cancer Checklist

Checklist for Needing BRCA Testing

As part of Breast Cancer Awareness Month, our goal is to disseminate information about high risk Breast Cancer.  The most important question that needs to be answered is

What is my risk for developing Breast Cancer?

The need for further genetic testing and strategies for prevention start with answering this question.  It is a fairly difficult question to answer.  Most women are inaccurate in determining their risk for breast cancer.  We use a comprehensive statistical evaluation tool that looks at all risk factors for breast cancer to determine if an individual falls into the high risk category or not.  For a more detailed look at breast cancer risk factors see out other post. Breast Cancer Risk Factors

Breast Cancer
BRCA Testing Saves Lives

Table of Breast Cancer Risk Factors: http://geneticmedicineclinic.com/dev/breast-cancer-risk-factors/

Indications for Breast Cancer Genetic Testing

If you have numerous factors that place you in the high risk category or if you answer yes to any of the questions in our checklist below:

  • Do you have bilateral breast cancer?
  • Do you have breast cancer < age 45?
  • Are there two members of your family with breast and/or ovarian cancer?
  • Do you have ovarian cancer?
  • Are you of Ashkenazi Jewish ethnicity?

What tests diagnose high risk Breast Cancer?

Here is a nice video from Ambry Genetics, one of our testing partners on BRCA1 and BRCA2

Genetic Testing for BRCA

BRCA Testing
Breast Cancer Counseling

Genetic Testing for the BRCA genes in Hereditary Breast and Ovarian Cancer

is an important method for identifying patients who are at high risk.  The difficulty has always been identifying those at high risk.

Testing only Women with a family history of breast or ovarian cancer will identify only half the women with mutations

There becomes two issues: 1: Identifying Women at High Risk for Breast and Ovarian Cancer and 2:The established criteria where insurance will pay for testing.

The National Comprehensive Cancer Network (NCCN) criteria for patients who should have BRCA1 and BRCA2 testing are:

Family History of Breast Cancer
  • Relative with a previously identified BRCA1 or BRCA2 mutation
  • 1st/2nd-degree blood relative who meets any criteria in below sections
  • 3rd-degree relative with breasta and/or ovarianb cancer and ≥2 close blood relativesc with breast and/or ovarianb cancer
Personal History of Breast Cancera
Age at Diagnosis Additional Criteria (only 1 of the following is necessary)
≤45 y
  • No additional criteria necessary
≤50 y
  • ≥2 primary breast tumorsd
  • ≥1 close blood relativec with breast cancer
  • Limited family history
≤60 y
  • Breast cancer that is negative for ER, PR, and HER2 (triple negative)
Any age
  • Patient is male
  • ≥1 close blood relativec with breast cancer diagnosed by age 50 or with epithelial ovarian cancer diagnosed at any age
  • ≥2 close blood relativesc with breast cancer
  • ≥2 close blood relativesc with prostate cancer (Gleason score ≥7) or pancreatic cancer
  • ≥1 close male blood relativec with breast cancer
  • Ethnicity (eg, Ashkenazi Jewish) associated with higher mutation frequency
Personal History of Other (Nonbreast) Cancers
  • Epithelial ovarian cancerb
  • Pancreatic or prostate cancer with ≥2e close blood relativesc diagnosed with breast, ovarian,b pancreatic, or prostate cancer (Gleason score ≥7)

Breast Cancer Risk Factors

Breast Cancer

Breast Cancer Risk Factors

We published a paper almost a decade ago in the Journal of Women’s Health which showed that most women were very INACCURATE in determining their breast cancer risk.  This conclusion was surprising because there is a wealth of information about breast cancer available on the internet, through health and medical websites and from health-care practitioners who are much more educated about Breast Cancer then they were in the past.

Why are Women mistaken about their Breast Cancer Risk?

From our study, it turns out that most women were somewhat familiar with Breast Cancer risk factors but were unable to understand how these risk factors should be weighted to determine a cumulative or combined risk.  For example, despite as strong family history of Breast Cancer (which increases breast cancer risk substantially), daily exercise was given as a reason for a woman believing her risk was minimal.  What she did not understand is that although daily exercise can reduce risk, it does not offset the tremendous increase in risk due to genetics and heredity.

 

 

List of Breast Cancer Risk Factors

Risk Factor Decreased Risk Slight Increased Risk Significant Increased Risk
First Degree Relative (Mother, Sister) with breast cacner  

↑↑

Mostly Jewish Ancestry    
Height > 5’7”    
Weight gain of 20-40 lbs since starting period    
Weight gain >40lbs since starting period     ↑↑↑
Birth Weight > 8.5 lbs    
Periods starting at age 15 or greater    
Given birth to two or more children    
First child born after the age of 35      
Diagnosis of benign breast disease  
Menopause starting greater than age > 55    
Oral Contraceptive Use    
Use of Estrogen for > 5 years    
Use of Estrogen/Progesterone < 5 years    
Use of Estrogen/Progesterone >5 years     ↑↑↑
Alcohol use > 1 drink/day    
Daily Exercise > 30 min    

Tamoxifen use > 5 years

   

For a Comprehensive Breast Cancer Risk Assessment, CONTACT US Map: https://goo.gl/maps/WYIkW Telemedicine or Video Consultation @ CLICK HERE

Tests You should have with Alzheimer’s Disease

brain

Testing in Alzheimer’s Disease:

is often confusing since the diagnosis is usually a clinical diagnosis.  Most importantly, laboratory tests should be performed to rule out other conditions that may be contributing to the dementia.

Blood Testing should include the following:

  • Complete Blood Count (CBC)
  • Vitamin B12 (Cobalamin) levels
  • Liver Function Tests
  • TSH and Thyroid Panel to rule out thyroid disease
  • RPR
  • Vitamin D Levels

Imaging

The American Academy of Neurology recommends

  • MRI or noncontrast CT scan
  • Electronecephalography (EEG)
  • Cerebrospinal Fluid Levels (CSF) measurements in only select patients.
  • CSF  biomarkers tau and amyloid are only available on a research basis

APOE Genetic Testing

APOE is not useful as a tool to make a diagnosis.  However, APOE increases the odds of a positive diagnosis when there is also a positive family history.

In addition, APOE genotyping can help confirm that Alzheimer’s Disease is the correct diagnosis.

 

A Typical Genetics Consultation

genetics consultation

What to Expect with a Genetics Consultation

The goal of a Genetic Consultation can be for Diagnostic, Disease Management and Optimization or Counseling purposes.  As we learn more about the role of genes and their contribution to birth defects, diseases, disease risks, and medication metabolism (pharmacogenetics), we can use this information to provide Personal Medicine and Precision Medicine.

Before the Genetics Consultation or Genetics Visit

A Genetics Consultation is more involved than a typical medical office visit.  To assess the role of Genetics in the disease process, we need a lot of information in order to make the most of your visit.  Typically, visits may last from 60-90 minutes.

Before the appointment:

  • Write down your main questions and what you would like answered
  • In advance, please have your medical records sent to us so they can be reviewed prior to your visit
  • Please ask your family members and get as much family health history as possible
  • Please bring all of your medications or a list of them with dosages

What to Expect during your Visit

  • A review of your Medical History
  • A review of your pregnancy and childhood history
  • A review of your developmental history
  • A review of your family history
  • A Physical Examination
  • A review of your Laboratory testing, x-ray studies and any other testing you may have performed

Genetic Counseling

Depending on your condition and the reason for your visit, anticipate that we may begin the education process to help you understand the:

  • Role of genes and heredity in contributing to the disease process
  • Risk of disease manifestation and disease recurrence and risk of transmission to other family members
  • Different testing options and the advantages and disadvantages of each
  • Prognosis and options for management

For more information about our Genetics Consultation services, please contact us at 855-474-8522

To refer a patient for Genetics Evaluation Services, please fax a Referral Request to 877-465-6936

Genetic Medicine Clinic | TeleGenetics |Personalized Medicine | 352-235-9636

How Good is the Color Genomics BRCA Test?

Angelina Jolie Breast Cancer, BRCA test

Color Genomics announced a $249 BRCA test today and the phones have been ringing all day.  The questions we have fielded all day:

1. Should I get it?

2. Why is it so cheap? Is it any good?

In fairness, we have not had any patients who have taken the Color Genomics BRCA or more accurately the Breast/Ovarian Cancer panel.  But we have reviewed their website and the white papers they offer.

The Genes:  Color Genomics analyzes 19 genes associated with hereditary breast and ovarian cancer.  The panel of genes is appropriate and quite comparable to many of the competing Genomic Testing companies through which we normally order Cancer Predisposition testing.  We would have no difficulty in recommending this panel of gene tests for women with a high-risk for breast/ovarian cancer development.

Methods: Based on the white paper from Color Genomics, the methodology is appropriate and comparable to most other laboratories performing BRCA testing.  They use a next-generation sequencing strategy that includes two positive controls.  Like most labs, they have appropriate quality control checks built into the DNA extraction and downstream processing aspects of the testing. In addition, they have done a pretty robust validation with known specimens with alterations in the 19 genes involved in the BRCA panel and showed that they could identify the genetic variant as established by other independent laboratories.

Laboratory: We have not visited the laboratory, however, Color Genomics has the appropriate regulatory stamps.  Having worked with lab reviewers and individuals involved in laboratory regulation, this is no small feat.  Color Genomics is CLIA certified (The federal regulatory body) and also adheres to quality control guidelines established by the College of American Pathologists.

Conclusion: Color Genomics appears to be a very legitimate laboratory offering BRCA testing at a very affordable price.

Concerns:  Our main concern is that this testing can be ordered and purchased directly online.  We are actually big proponents of giving patients autonomy over their testing decisions so the part that worries us is that for those that order directly, Color Genomics claims that it is a Physician ordered test.  That means, these individuals are assigned a Physician who technically is ordering the test, however, the reality is that the test ordering and process have begun prior to any real Physician interaction.  We are not as concerned about doing testing in low-risk women like many of our Cancer Colleagues because we firmly believe knowledge is power and as long as the test is recognized as being part of the educational process to making healthcare decisions then we say go for it.  However, we think that having a relationship with a health-care provider in advance of testing provides great benefit.  Testing is done for a variety of reasons and the reason and impetus for testing need to be considered both before the test is initiated and very importantly, afterwards.  Genetic testing information is very different from other physiological tests.  A calcium level is just that a calcium level that may indicate disease or health and represents a snapshot in time.  Genetic information, on the other hand, is permanent.  Knowledge gained about your risks cannot be undone.  Any Geneticist or practitioner in the field will tell you of plenty of cases, where the genetic information had adverse consequences for the individual and the family.  It can impact mental health, family dynamics and relationships and may result in significant changes in attitudes and approaches towards life.  Consequently, we always recommend having a conversation with a care provider in advance so there is a discussion about risks, the impetus for testing and what the individuals health-care goals are.

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