Author: Maulik Shah MD PhD

BRCA Testing for Breast Cancer Awareness Month

Breast Cancer

Goal of Breast Cancer Awareness Month – Get BRCA Tested if you have a Family History of Breast or Ovarian Cancer


Breast cancer is the most common cancer in women, affecting one in eight women in their lifetime for a background population risk of 12.5%. In the US, last year, the national Cancer Institute estimated 231,840 new cases of female breast cancer. The majority of breast cancers are sporadic meaning there is not an inherited component. However 5 to 10% are due to inherited causes.

Although BRCA1 and BRCA2 were the first genes identified to be associated with this inherited risk for cancer they are only responsible for about 50% of hereditary breast cancer. However, additional genes have been discovered that are associated with increased breast cancer and ovarian cancer risk and with these other genes there is often other cancers such as pancreatic cancer, thyroid cancer or sarcoma in the family.

Genetic Cancer Risk

Indications for breast cancer testing

  • Early-onset breast cancer
  • Having a male relative with breast cancer
  • Having a history of breast and ovarian cancer in the same individual or in closely related family members
  • Multiple members of a family with breast cancer
  • Multiple members of the family with breast, uterine or thyroid cancer

Benefits of testing

Early detection improves the odds of survival


cancer survival





In addition, identifying and inherited susceptibility for certain cancers can change both screening and management of your health

  • Earlier acceptance of screening tools such as mammograms, ultrasound and MRI
  • Indication for risk reducing measures such as ovary removal after childbearing is complete
  • Identify other at risk family members
  • Consideration for medications for primary risk reduction

Expanded BRCA Test Panel – Now Available for Breast Cancer Awareness Month

Test description – our advanced BRCA panel includes BRCA1, BRCA2, CDH1, PALB2, PTEN, TP53 and many other genes associated with the increase risk of breast and ovarian cancer. In fact the current panel consists of 30 genes and represents a comprehensive genetic analysis for hereditary cancers including breast, ovarian, colorectal, pancreatic and other cancers as well.
Testing is performed in a CLIA certified laboratory with strong performance standards showing 100% accuracy, 100% sensitivity, 100% specificity with both repeatability and reproducibility

This Expanded BRCA Panel can be ordered on our Facebook page



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


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%


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

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

Breast Cancer in Men


Men with Breast Cancer?

Say it isn’t so.  But yes it is.  Men can and do get breast cancer.  There were about 2500 cases of breast cancer in the US last year.

male breast cancer

What kind of symptoms do men with breast cancer get?

In men, breast cancer is usually a PAINLESS lump.  Usually it is hard and does not move and is in the area just around the nipple.  The lump can be deep and does not need to be on the surface of the skin.  Since men don’t usually check their breast or chest area, breast cancer is usually advanced in men by the time of diagnosis.  Most men have advanced stage III or IV disease by the time they get diagnosed.

As a man, am I at risk for Breast Cancer?

You may be at risk for breast cancer if there are other family members with breast cancer.  If you have two or more members of your family with breast or ovarian cancer or breast cancer at a young age, it would be advisable to first test the affected family members for the BRCA1 or BRCA2 genes before getting tested first.



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:

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: Telemedicine or Video Consultation @ CLICK HERE

Confirmation of Mast Cell Activation Disease

Mast Cell Activation

Mast Cell Activation Disease

is often difficult to diagnose.  Much of the diagnosis requires clinical signs and symptoms and criteria have been established (see excellent Journal Article in Journal of Hematology and Oncology by Molderings et al.). However, Mast Cell Activation can also be a sequelae of other disease processes as seen recently in a patient with CD8 promoter genetic mutations where the Mast Cell Activation was a consequence of CD8 immune dysregulation.

So confirmation of Mast Cell Activation Disease is important.  Often a diagnosis requires a tissue biopsy showing elevated numbers of Mast Cells.  In many individuals the problem becomes that they may not have active disease at the time of biopsy or they are usually on anti-histamines or immunosuppressants by the time a need for a tissue diagnosis is required.

Recently, Ravi et al. published in the Journal of Allergy and Clinical Immunology, a paper showing that Mast Cell Activation Disease had differing levels of biomarkers and that a combination biomarker approach resulted in the most sensitive method for disease confirmation.

In their study, they evaluated patients with MCAD by measuring serum tryptase, and urine N-methyl-histamine (NMH) and 11B-prostaglandinF2 (PGF2A).

Tryptase levels were only elevated in about 40% of patients and NMH was elevated in less than 10% of patients.  In contrast, PGF2A and Tryptase levels together were elevated in the majority of patients with MCAD.

Importantly, since PGF2A is in the inflammatory process, it highlights patients that may benefit from Aspirin as a means to block this pathway (More on this later).

Overall, the diagnosis should still require clinical criteria.  However, tryptase and PGF2A can be used for confirmation in some patients.  Most importantly, PGF2A can be used to identify patients with auto-inflammation in the prostaglandin pathway.



Tests You should have with Alzheimer’s Disease


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


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.


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