Genetic Testing

It is clear that you may possibly have a predisposition from your family history and yourself that there may be a genetic mutation running in your family. You did not say how old were you when you were diagnosed with your breast cancers. Or what ethic background you have or how old were your relatives when they were first diagnosed with breast cancer.

We all have breast cancer genes in our bodies that are supposed to protect us from breast cancer. People who have the BRCA1 mutation, BRCA2 mutation has a higher risk of getting breast cancer and or ovarian cancer, because the mutation comes from your mother or father and you can receive them at the time of your conception. However, because a person may have the mutation, it does not mean that they will get these cancers in their lifetime.

The BRAC Analysis Rearrangement Test (BART) is an additional level of analysis, which goes beyond DNA sequences of genes. Having this additional test, one has to look at the risk and benefits of this test for you. If you are searching for answers of why breast cancer is prevalent in your family and feel that this test will help resolve issues that are concerning your health, perhaps you should speak to a genetic counselor and your oncologist about this test.

Genetic testing can mean several things. Testing a patient’s melanoma for the presence of a BRAF or C-KIT mutation can be done anytime, although it is important to have those results before starting a BRAF or C-KIT inhibitor. Genetic testing is also being investigated in families where 3 or more members have had melanoma. This type of genetic testing has less of a direct impact on the therapies we choose, but it will, some day, help our understanding of why certain people are at risk for the disease.

Genetic mutations play a key role in NSCLC. Identifying certain, key mutations can help select targeted therapy. The two most important mutations in lung cancer right now are the EGFR and EML-4ALK mutation and are found in the subtype of lung cancer called adenocarcinoma. These mutations are more commonly found in female, asian, non-smokers. However, they are also found in smokers and males, but to a lesser degree.

Patients with the EGFR mutation are generally treated with a drug (pill) called Tarceva as first line treatment, rather than chemotherapy. Similarly, patients with the EML-4 ALK mutation are treated with a recently approved drug (pill) called Xalqori (Crizotinib). Generally patients with these mutations who are treated with the appropriate drug do very well when compared to patients who don't have the mutation and are treated with chemotherapy

Due to the dramatic responses with the use of these drugs when a mutation is identified, it is important to test for these mutation at diagnosis. Generally, when the initally biopsy is done, I make sure that there is enough material left over to send for molecular testing. It takes roughly 2 weeks to get the results back, so based on patient preference, I may start the patient on chemotherapy until the results come back.

To note, the testing of these mutations should routinely be performed in patients with stage IV NSCLC, not in patients with stage I-III (yet). Outside of a clinical trial, there is just not enough evidence yet on how to use these molecular markers in stage I to III NSCLC although this may change very soon.

I think the first thing that must be said about BRCA testing is that I sat with a social worker who specialized in the potential emotion impact of the results of genetic testing. Even though I already had a cancer diagnosis, had I tested positive for the gene, I would now have my daughter with a burden over HER head. To test or not. And when? I had enough of a family cluster of disease from a fairly detailed pedigree. I made all my treatment choices before I even got the results.

When the test came back with mutations of unknown significance on BOTH BRCA1 and BRCA2 I was stunned. Immediately, my mom was tested and she tested completely clean. She was the one with the first breast cancer but NO mutations. I sat with the social worker and the head of genetics to review the results and what they meant. He explained how "a mutation starts somewhere" so I could have inherited from my dad or I could simply be the first person with that particular mutation.

I remember how weird it was to see the results because they were so detailed (stuff I do not remotely understand) but what struck me was the fact that they indicated the number of times they had previously seen the mutation and why they couldn't classify them as "cancer causing genes" ..... and they also couldn't classify them as harmless either. One of them was seen seven times before me. The other one, they never saw before. I was the first. Last year, my youngest sister was dx'd with DCIS right on her chest wall. She tested for the gene and she was clean on one but matched the other one..... obviously came from dad.

It's a little frustrating to have a test done and basically be told, it could be something, it could be nothing or because of the family cluster of disease, it could be a gene not yet identified. Because I had been counseled through all of these scenarios, I was okay with still having no answer.

I know that I will be notified once these genes are classified and hopefully, both of them will be harmless so my daughter is off the BRCA hook. Unfortunately, she is still a "previvor" because of my family cluster.

A bit confusing to answer, but then that's exactly what the results were.... they took an entire page filled with four paragraphs to say, "we don't know" .... Since I tend to be the wordy one, every once in a while it will cross my mind and I'll laugh. Sometimes, you just gotta laugh.

One can divide the answer to this question into two parts, firstly, patients who have been diagnosed with breast/ovarian cancer, and secondly, unaffected family members.
For the first part I will list the current (April 2011) NCCN guidelines for BRCA 1 and 2 testing:
Women aged 45 or younger at age of diagnosis of breast cancer.
Women aged 50 or younger with 2 breast cancers, first cancer diagnosed less than 50 years of age.
Women aged 50 or younger with breast cancer with a close relative diagnosed with breast cancer age 50 or less (or ovarian cancer any age).
Women aged 50 or younger with breast cancer and limited family structure.
Women aged 60 or younger with triple negative breast cancer (ER,PR, Her-2-neu negative).
Woman with breast cancer at any age and 2 other family members with breast, ovarian or pancreatic cancer.
Woman with breast cancer at any age and one male family member with breast cancer.
For unaffected individuals who have a relative with a known BRCA1 or 2 mutation, site specific testing can be done. In families in whom there are no affected individuals still living, then the person whose result would yield the most meaningful information should be tested first. For example, if an unaffected patient came to me with a family history of four paternal aunts with breast cancer, all deceased, and an unaffected father still living, then the father should be tested before his daughter. If he tests negative, there is no need to test his daughter.

Great question. "Automatic" implies knee-jerk, and, as with most patient-related issues, the answer is "it depends." BRCA positivity confers a lifetime risk of ovarian cancer of 25-40%. Oophorectomy is the best prevention for ovarian cancer, therefore oophorectomy should be discussed with and offered to all female carriers of a deleterious mutation. The prevention is not absolute however, and primary peritoneal cancer can still occur after prophylactic oophorectomy. The issue really is timing. When to do the procedure? Questions need to be asked. How old is the patient? Have they completed their family? Do they plan to have more children?
I counsel my patients who are carriers of deleterious mutations to have prophylactic oophorectomy by age 40. In the meantime, I advise regular bimanual pelvic examinations, transvaginal ultrasound exams and CA125 levels.

I was thinking about having genetic testing after losing my mom to breast cancer. She was BRCA2 positive. I thought I had a bit more time to contemplate my decision. As it turned out, I did not. A short time after she died, I was diagnosed with breast cancer myself. After my diagnosis, there really was no other reasonable course of action other than going ahead with the testing. I needed tests results to determine my course of treatment. If I had not been diagnosed with breast cancer, I probably would still have decided to go ahead with the test. In addition to my mom, I also have three aunts who had breast cancer on my mom's side and one or two on my dad's side as well.