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