BRCA Mutations

I am seeing increasing numbers of women these past few years who are undergoing prophylactic mastectomies who are BRCA positive. However, even if a woman is BRCA negative, there may still be a very valid reason for prophylactic mastectomies, such as a very strong family history of breast cancer. In such a case, it is important to discuss the decision with your breast surgeon and other members of your health care team, as there are certainly many factors to be considered in the decision that can best be answered by those who know the specifics of your situation.

Due to the high risk of breast and ovarian cancer, most will recommend mastectomies and then ovary and tube removal as soon as child bearing is completed. This is the greatest risk reduction but is still not 100%. There is no consensus on how to follow patients with mutations regardless of cancer diagnosis or not. The NCI is currently doing clinical trials for patients with known mutations to try and answer this question. Here's a link: http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA#a18

Tough question...
I have to say that the most difficult issue is wondering how many other family members have inherited this gene mutation.
I deal with all issues in my life in a positive way. I am a very positive person & I ALWAYS look for the funny & the good in life.
I try to enjoy every day & help others. I love my friends & my family.

Olaparib was developed to specifically target PARP, which becomes more critical in cancers that develop as a consequence of an inherited mutation in the DNA-repair genes. Its activity is largely confined to those breast and ovary cancers that have defective BRCA genes on the basis of inheritance. It could similarly be active in other cancers, such as Pancreatic, that are associated with these genetic defects but more data is needed.

Risk of recurrence will depend in staging (tumor size and presence or absence of nodal metastases).

Your chance of developing a new primary breast cancer has been greatly reduced by having a bilateral mastectomy.

A study by El-Tamer et al Ann Surg Oncol. 2004 Feb;11(2):157-64 found no difference in overall survival and breast-cancer specific survival between BRCA mutation carriers and non-carriers.

You choice to have bilateral mastectomy has certainly reduced the likelihood of a new cancer in the same breast and vastly reduced the chance of a cancer in the opposite breast. Adjuvant chemotherapy (and hormonal therapy when indicated) has reduced your chance of recurrence. Oophorectomy has diminished your chance of ovarian cancer.

It would be glib to say "don't worry". I just read an article by a survivor of endometrial cancer who thinks about her cancer 24/7. Thinking about cancer will be inevitable for someone who has undergone treatment. I advise my patients to reverse their thought process, think about the cancer not coming back, rather than it coming back.

I strongly recommend regular exercise, which has been shown to reduce recurrence rates.

When a patient misses a followup appointment with me, it means they are not dwelling on their cancer, and are off doing other things, and that's good.

There are many foods, herbs, supplements & lifestyle choices that reduce the possibility of the BRCA-1 or 2 gene from being expressed. If you're in the NY/NJ area, on Saturday October 15th in Montclair NJ come attend this free symposium. I'll be speaking on some of those issues/recommendations. http://www.montclairbreastcenter.com/wellnessevents.htm

The following information is from the site Facing Our Risk: http://www.facingourrisk.org/index.php - a national nonprofit organization devoted to hereditary breast and ovarian cancer.

"Women with a BRCA mutation or other hereditary breast cancer who choose breast conservation to treat their breast cancer are at higher risk for another cancer in either breast than women with sporadic breast cancer. Although the exact risk depends on a woman’s age and other factors, one study found that BRCA carriers diagnosed with breast cancer have a 14% chance within ten years of developing the disease in the same breast, and a 37% chance within ten years of developing the disease in the opposite breast. Another study found a 40% chance for BRCA carriers to develop cancer in the opposite breast within ten years of their initial diagnosis. The risk for a second breast cancer among women who develop sporadic cancer is about 10%."

I made the decision after the blood was drawn but before I got the results. The results didn't matter to me, I know for a bunch of reasons, it was the right choice for me. My ovaries/tubes were removed when they did the exchange surgery on the reconstruction. Thing is, I knew I was done having kids.

Yes, knowledge is overwhelming which is why the BRCA testing is so hard to deal with. You are young. I do know statistically, they worry more about younger women and ovarian with BRCA 1. With BRCA 2 mutation, the ovarian seems to happen later. According to the head of genetics at Sloan Kettering who counseled me, the BRCA 2 is more late 40's or even 50. Of course, there are always the exceptions which is why it requires such careful thought and consideration.

I'm wondering if you explored the option of harvesting eggs. I don't know enough about this to do anything other than throw it out there. You don't need your ovaries to carry a child. When you are done exploring, talk to someone about all all the options and then just think about everything. Only you can decide. I hate that you are living with this... and this is exactly what troubled me. Knowing if I was "absolute" positive, what does my daughter do.... she was 21 when I was dx'd.

We can TALK when you get to NY!!!!

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.

BrCa 1 is more often associated with estrogen and progesterone receptor protein NEGATIVE tumors and are also more often her-2-neu negative (triple negative) than tumors seen in sporadic (non hereditary) breast cancer. BrCa 2 tumors are more like sporadic breast cancers in their molecular signatures.

Myriad Genetics (http://www.myriad.com/) has had BRCA 1 and 2 testing available since 1996. Currently there are over 2000 variations in BRCA 1 and 2 genes that have been shown to be "deleterious" mutations, in that they are responsible for an increased risk in breast and ovarian cancer. New deleterious mutations are being discovered and confirmed with some regularity.

At this point, approximately 5% of mutations identified are labeled "mutations of undetermined significance" - this means that there is a gene abnormality, but there is not enough data to know if the mutation is a harmful one or not - realize that many gene mutations do not confer an increased risk. According to one of the researchers at Myriad, when they first started testing in 1996, "15 to 40% of the people getting tested had a variant of uncertain significance. That is now under 5%, because we have made enormous progress in our ability to study variants and figure out if they cause an increased risk for cancer. But there are still a lot of variants for which we need more information".