`"You recognize a survivor when you see one. You recognize a fighter when you see one." ~Elizabeth Edwards
 
Testing for Genetic Risks of Cancer

In the past I have referred patients that I have identified as high-risk for hereditary cancer for genetic counseling, but I have been persuaded by the evidence that 80% of patients referred for counseling/possible testing do not follow this recommendation.  Instead of risking missing an opportunity to obtain critical information on these patients, I began offering the testing from my gyn office.​  

Most cancer occurs by chance. This is often called “sporadic cancer.” In some families we see more cancer than we would expect by chance alone. Determining which of these families have cancer related to an inherited gene mutation is important, as the cancer risks in hereditary cancer families are much higher than the general population.​
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• Hereditary cancer is caused by an inherited genetic mutation. It is typical to see a recurring pattern of cancer across two to three generations—like multiple individuals diagnosed with the same type of cancer(s) and individuals diagnosed with cancer much younger than average.
• Familial cancer refers to cancer that appears to occur more frequently in families than is expected from chance alone. While no specific mutation has been linked to these cancers, familial cancer may have a hereditary component that has not yet been identified.
• Sporadic cancer refers to cancer that occurs due to spontaneous mutations that accumulate over a person’s life. Sporadic cancer cannot be explained by a single cause. There are several factors, such as aging, lifestyle, or environmental exposure, that may contribute to the development of sporadic cancer.

We can currently test for breast/ovarian and Hereditary Colon cancers with genetic testing done by a simple buccal swab or blood test.  This is only done in patients identified with increased risk for hereditary cancer. (About 10% of patients screened by a personal and family history questionnaire.)  If you'd like to try the Hereditary Cancer Quiz at home, see this link.

Gene mutations passed from parent to child can drastically raise the risk of disease, including many types of cancer. In fact, patients with certain rare hereditary cancer syndromes may have an up to 100 percent chance of getting certain types of cancer.
The ongoing discovery of genes involved in cancer allows us to test for cancer-causing mutations in these genes, which may increase cancer risk. If your patient has a mutation that puts him/her at an increased risk of cancer, you can take action to help reduce the risk of cancer through increased surveillance, chemoprevention, prophylactic surgery and counseling about risk. Identifying the potential risk of cancer is the first step in determining the best way to possibly delay, or even prevent, the development of certain cancers.*

Genetic testing for hereditary cancer tests provide vital information to help those with a personal or family history of cancer understand the risk of developing disease. Armed with the results of genetic testing, you can take steps to potentially prevent the disease, delay its onset, or catch it at an earlier stage when outcomes are likely to be better. This information can help improve health and quality of life while reducing healthcare costs.

These patients usually develop cancer at a young age or have cancer in their families that occur at a young age (e.g., below 50). Patients may also have cancer that occurs in several family members or multiple times in the same individual. The cancers can be found in the patient and/or on either the maternal or paternal side of the family.

Who may have a mutation that increases risk of cancer?
Most women who get breast cancer do not have an inherited BRCA gene mutation. The chance that you have a BRCA1 or BRCA2 gene mutation is greater if one or more of these statements is true:

• you were diagnosed with breast cancer at an early age
• your mother, sister or daughter was diagnosed with breast cancer under age 50 or ovarian cancer at any age
• a woman in your family has had breast and ovarian cancer
• a woman in your family has had breast cancer in both breasts
• your family is of Ashkenazi Jewish descent
• a male in your family has had breast cancer.

How often is a BRCA gene mutation the cause of breast cancer?

As above, most breast cancers are not linked to inherited mutations, they are sporadic..
Only about 5 to 10% of all cases of breast cancer in the United States are due to inherited gene mutations

Can I find out if I have an inherited gene mutation?

Yes, you can. Women who think they may qualify for genetic testing because of family history of breast or other cancers (ovarian, endometrial, colon, melanoma, prostate, pancreatic, brain, kidney, stomach, small bowel) should discuss this with their physician.  We are trained to gather a woman’s family health history through a screening as well as explain the results of the genetic test results.  In most cases, the test is done first on the survivor, if available. 

If no error is found, the cancer was not likely due to a mutation, (or due to currently known mutations.)  In this case, no further testing of other family members is needed.  If she is not available or not willing to be tested, her family members should consider being tested.

Should I?

SGO Updates Hereditary Cancer Recommendations as of March, 2014
Some of the key aspects of the statements include:

• A recommendation that women diagnosed with epithelial ovarian, tubal and peritoneal cancers should be considered for genetic counseling and testing even in the absence of family history
• A recommendation that all women diagnosed with endometrial cancer should undergo systematic clinical screening (review of personal and family history) and/or molecular screening for hereditary colon cancer risk
• An acknowledgement of the advantages of cancer gene panels including decreased cost, improved efficiency, and the fact that a negative genetic test is more reassuring because it eliminates concerns about an inherited risk for all known genes. 
• Hereditary cancer testing for gynecologic cancers has been underutilized compared to breast cancer despite the fact that ovarian and endometrial cancer patients are at higher risk for hereditary cancer.  Myriad estimates that less than 25% of women with ovarian cancer and fewer than 5%of women with endometrial cancer receive hereditary cancer testing.

The process:

1. You provide a thorough family health history through a specific form genetic screening form at time of your annual exam.
2. Pre-test counseling will be done to help you decide whether or not to proceed with genetic testing. This counseling includes:an overview of the procedure: a review of the risks and benefits of genetic testing, such as cost, (most insurances cover the cost for candidates of testing: and Ambry the testing group, will fight for you), privacy and the potential knowledge that you carry the gene mutation, a discussion of what you will do with the information once you know the test result, a discussion of the emotional impact of this information, as well as implications for your family
3. If you decide to proceed with testing, we obtain a blood sample in our lab. You and the nurse will fill out more paperwork.
4. The sample is picked up by courier to be sent for testing. It usually takes 3-4 weeks to obtain results.
5.  Interpretation of the results will be explained to you by Dr. Malley.  Together you will review results and implications for your future surveillance and management.

Effective strategies for breast & ovarian cancer risk-reduction:

Include cancer surveillance, risk-reducing surgery, and/or chemoprevention. For women who have not undergone risk-reducing surgery, breast and/or ovarian cancer surveillance entails:

• Monthly breast self-examination beginning at age 18.

• Clinical breast examination 2-4X/year beginning at age 25.

• Annual mammography and breast MRI (commonly alternated every six months) beginning at age 25 or individualized based on the earliest age of onset in the family.)

• Women between the ages of 25 to 30 may consider MRI only, with annual mammography added after age 30.

• Ovarian cancer screening: thus far the best screening available: twice a year we will send you for a transvaginal ultrasound and serum CA-125 levels (preferably day 1-10 of menstrual cycle for premenopausal women) beginning at age 30, or 5 to 10 years earlier than the earliest age of first ovarian cancer in the family

What about prophylactic mastectomy?

Risk-reducing mastectomy is a highly effective strategy for breast cancer risk reduction, decreasing the incidence of breast cancer by as much as 90% or more in patients at risk of hereditary breast cancer.  It should be considered by women with a BRCA1 or BRCA2 mutation.  For example, actress Christina Applegate was tested for these mutations based on her family history.  When she tested positive for the BRCA 1 gene mutation, she underwent a prophylactic bilateral mastectomy.  After the surgery was completed and tests done on the removed breast tissue, it was discovered that she had very early breast cancer.  Her courage to act likely saved her life.
 
Is there a benefit to removing the ovaries in BRCA+ patients?

In short: yes.  It reduces the risk of both breast and ovarian cancer. Risk-reducing removal of ovaries and fallopian tubes ("bilateral salpingo-oophorectomy" or BSO) is highly effective in reducing ovarian and fallopian tube cancers in both BRCA1 and BRCA2 mutation carriers (by approximately 80 %) and breast cancer in premenopausal women.

This surgery is recommended for BRCA+ patients by age 35 to 40 or when childbearing is completed, or individualized based on age of onset of ovarian cancer in the family.

BRCA+ patients who choose not to have surgery

Intensive surveillance and the consideration of using tamoxifen as a chemoprevention, though the benefits of tamoxifen in BRCA1 carriers are unclear. This is less effective than prophylactic mastectomy, but several studies show decreased risk of breast cancer.

Benefits and Limitations of Testing

Benefits

• Personalized hereditary cancer risk assessment
• Information to help make medical management decisions to help reduce cancer risk
• Important information for family members to help determine their risk
• Reduced anxiety and stress

Limitations

• Testing does not detect all causes of hereditary cancer, nor eliminate risk of cancer
• A negative result is most helpful when there is a known mutation in the family.​​
• Testing may increase anxiety and stress for some individuals. 
  
• Results in some cases may return inconclusive or uncertain.