In March, like millions of people, I sat enrapt watching the three-night premier of the documentary by Ken Burns, “Cancer: The Emperor of All Maladies.” As you know cancer is very personal to me. I have “battled” and “survived” the diagnoses of multiple tumors for more than twenty years. I am not a doctor or scientist but a “career” cancer patient. I have had different bilateral breast cancers, pancreatic cancer and two different types of lung cancer. I have had many other rare but benign tumors as well. I used to think I was cursed but now I think I am lucky.
I was tested for hereditary cancer syndromes such as BRCA1 and BRCA2, Cowden’s Syndrome (a PTEN gene mutation) and Peutz-Jeghers Syndrome (a STK11 gene mutation). The latter two are tumor suppressor genes. A few others tests were thrown in. Nothing was found.
Within the past 5 years my young adult daughter was diagnosed twice with leiomyosarcoma, a more rare form of cancer. It was only after her first diagnosis and because she had a sarcoma, that she and I were tested and learned we had Li-Fraumeni Syndrome (LFS).
LFS is a hereditary cancer syndrome, a mutation of the p53 gene. This means that there is one copy of the mutated gene in the DNA of every cell in my body. P53 is known as the “Guardian of the Genome” and is the major tumor suppressor of our DNA. Very basically, p53 is activated when a cell is dividing. It reads the DNA coding and checks for errors. If there is an error, it initiates repairs. If the code isn’t repaired, p53 sends a signal for the cell to self-destruct. With my mutation, simply put, this doesn’t work. The mutation creates a dead end early in the process.
I was born with this mutation. Therefore defective cells can proliferate unchecked. This has led to multiple primary cancers. The risk for a person with LFS to develop any type of cancer before age 60 is 90 percent. Approximately 50 percent of these cancers will be diagnosed before age 30. If you have this mutation there is a 50 percent chance of passing it on to each of your children.
Much research has been done over the past few decades on the p53 gene. In fact, many dedicated cancer research scientists and doctors have spent their entire careers studying it. A mutation of this gene is implicated in approximately 50 percent of tumors in people that are not born with a mutation.
Our LFS family mutation, a change in a single base pair on this gene has given rise to breast, pancreatic, lung, and sarcoma cancers, so far. The most common cancers seen in people with LFS are pre-menopausal breast cancer, soft tissue sarcoma, osteosarcoma, brain tumors, adrenocortical carcinoma (ACC), and leukemias. I know people with LFS whose family history also includes cancers of the liver, kidney, prostate, cervix, ovaries, stomach, thyroid, and colon, as well as melanoma, lymphomas, rare cancers and many benign tumors. The question to ask: What cancers do families with LFS not get? Some families are affected at very young ages, some older. Some people with a known LFS mutation never get cancer. Therefore, research is key for all of us.
In my opinion, the key to living with LFS is the early detection of cancers. That happens by first knowing you have the mutation. Then you also must have regular and frequent screening of everything for the detection of tumors when they are treatable. The use of radiation and radiation-based screening is discouraged since it is known that it increases the likelihood of getting a tumor.
This is why I say I am lucky. I didn’t know. However, had I known earlier, my daughter would have been tested years before, she would have been screened using MRIs and her cancer would have be found at a much earlier stage. We have both had new cancers and surgeries since we found out about LFS, but so far so good. We are still here.
Li-Fraumeni Syndrome is considered a rare disease but I’m not so sure. I had four cancers and a daughter with cancer over the course of 17 years before I was even tested for it based on the LFS testing criteria guidelines, which I am happy to say, is continuing to evolve. Because of our circumstances, our family has access to top research hospitals where we live and the money to pay for the tests. I wonder how many people get cancer, even more than one cancer like me, and are never tested for this or any other genetic mutation? It seems absurd that today cancer patients are not being tested for this mutation due to lack of professional medical knowledge, patient access to qualified genetic counselors through referral (who are in short supply) and even worse, financial considerations. I know people in this country and around the world where some or all of the above are true.
Therefore, getting tested for LFS, unfortunately, is based on professional recommendation and patient knowledge is many times the driver. Having the financial ability to pay for this and other hereditary cancer tests when they may not be covered by insurance is an area in need of immediate reform. Current and relevant medical education about LFS and other hereditary cancer syndromes for all practicing surgeons and oncologists is critically important and needs beefing up especially where there is no access to world-class hospitals.
I believe whatever numbers are out there on the incidence of this or any other hereditary cancer syndrome are statistically biased, extrapolated and may be way too low. Currently the known number of families in the United States with LFS is approximately 400. Yet the incidence projected for having this mutation is 1 in 5,000 to 1 in 20,000! We also have about a 1 in 5,000 chance of being killed in a car accident and we hear about that all the time. We don’t know what we don’t know!
I am currently a participant in a clinical trial for LFS at the National Cancer Institute (NCI). Part of the study uses whole-body MRI as a means to detect cancers early and effectively. Since learning about our deleterious gene mutation, we made arrangements with the NCI to have all subsequent tumors removed preserved and shipped ‘live’ in liquid nitrogen, which is important for research. I coordinated with them to receive all of my earlier, paraffin-blocked lab specimens of other cancerous and rare, but benign tumors for tumor banking, storage and research.
At least twenty of our personal tumors are stored at the NCI. The study of the genetic, molecular, and cellular changes that have caused my cells to go from normal with a mutation, to abnormal, and then to cancer in all the tumors from me and now my daughter is not part of the current or any other research study that I know of. Why? Because the NCI does not have the funds to do the research!
Even though there are currently many respected, fervent researchers around the world devoted to the study of LFS, they are woefully underfunded as well. So much of cancer research funding relies on philanthropy and grants. Families with LFS have the burden of economic disaster, so while they are very involved and passionate, they are not able to drive substantial fundraising campaigns. Since LFS (we assume) is now and hopefully always will be (we assume) an orphan hereditary cancer syndrome, well, you get the rest.
I believe if researchers were funded more vigorously to study the DNA of families born with a p53 mutation, it may provide a key to the other drivers of oncogenesis, the formation of tumors. I loved the discussion on the ‘Finding the Achilles Heel’ episode of the Ken Burns series pertaining to the now known 12 main genetic pathways to tumor formation. The idea of breaking the chain at any point along the genetic pathway would stop tumor formation. This is what needs to happen even if it is difficult to accomplish. We can and we must do it!
In the case of people with Li-Fraumeni Syndrome, cancer is not a seemingly impossible “400 different diseases” as so eloquently put forth in the documentary: It starts as an autosomal dominant mutation on one gene, a mutated p53 gene that causes 400 different cancers.
I’m only a patient, yet a very experienced cancer patient, where living with cancer has become my career, not by choice, but for me to evolve before my cancer does.
Please call your congressional representatives to fund the NCI!
For information about LFS see http://www.ncbi.nlm.nih.gov/books/NBK1311/
Three major organizations that are currently set up to provide much more information, support for patients and families, as well as raise money for LFS research are: Living LFS, LFSAssociation.org and The George Pantziarka TP53 Trust.