Breast Cancer Predisposition and Risk Testing
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.
Early detection improves the odds of survival
In addition, identifying and inherited susceptibility for certain cancers can change both screening and management of your health
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
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:
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.
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.
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.
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
Table of Breast Cancer Risk Factors: http://geneticmedicineclinic.com/dev/breast-cancer-risk-factors/
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:
Here is a nice video from Ambry Genetics, one of our testing partners on BRCA1 and BRCA2
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.
|Family History of Breast Cancer|
|Personal History of Breast Cancera|
|Age at Diagnosis||Additional Criteria (only 1 of the following is necessary)|
|Personal History of Other (Nonbreast) Cancers|
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
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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