WHY BRCA PROJECT?
EARLY DETECTION SAVES LIVES!
“The BRCA gene is a mutation that is genetically passed down from either the father or mother”
Developing breast cancer is increased if the in BRCA1 or BRCA2 gene is inherited. Over the course of the general population, 12% will develop breast cancer. At Least, 55% of patients with BRCA 1 or BRCA 2 mutation will develop breast cancer before the age of 70. Breast Cancer is one of the leading causes of death among women.
“It is important to note that these estimated percentages of lifetime risk are different from those available previously; the ratings have changed as more information has become available, and they may change again with additional research. No long-term general population studies have directly compared cancer risk in women who have and do not have a harmful BRCA1 or BRCA2 mutation.
It is also important to note that other characteristics of a particular woman can make her cancer risk higher or lower than the average risks. These characteristics include her family history of breast, ovarian, and, possibly, other cancers; the particular mutation(s) she has inherited; and other risk factors, such as her reproductive history. However, at this time, based on current data, none of these other factors seems to be as strong as the effect of carrying a harmful BRCA1 or BRCA2 mutation.”
WHY IS IT IMPORTANT TO ME?
“THE BRCA GENE MUTATION EFFECTS BOTH MEN AND WOMEN OF ALL AGES AND HEALTH”
MEN ARE NOT SAFE FROM THE NEGATIVE EFFECTS OF THE BRCA GENE MUTATION.
Men who carry the BRCA mutation have a higher risk of developing cancer than men who don’t express the mutation in either BRCA1 or BRCA2 gene. Currently, the study and the effect of BRCA 1 and BRCA2 mutation for men are limited; research has shown that there is an increased risk of prostate cancer, skin melanoma, and breast cancer. Most men are not aware they carry the gene until they are diagnosed with either prostate cancer or breast cancer.
· About 50 out of 100 women with a BRCA1 or BRCA2 gene mutation will get breast cancer by the time they turn 70 years old, compared to only 7 out of 100 women in the general United States population.
· About 30 out of 100 women with a BRCA1 or BRCA2 gene mutation will get ovarian cancer by the time they turn 70 years old, compared to fewer than 1 out of 100 women in the general U.S. population.
WHY IS THE STUDY IMPORTANT?
The science behind the study.
We believe patients with BRCA1/2 mutations provide an excellent population to study the role of ISET CRCs in cancer screening because BRCA1/2 carriers have a high incidence of malignancy and limited options for cancer screening. The National Cancer Institute recommends that patients identified as carriers of BRCA1 and BRCA2, undergo “enhanced screening, prophylactic surgery and chemo-prevention”(8). Enhanced screening includes earlier breast examinations, mammograms and MRI for breast cancers starting at age 25(8,11). The NCI states that no effective ovarian cancer screening methods currently exist. Some groups recommend trans-vaginal ultrasound, blood tests for the antigen CA-125, and clinical examinations. These methods do not appear to detect ovarian tumors at an early enough stage to reduce the risk of dying from ovarian cancer and are not officially recommended by the NCI although they are mentioned on the NCI website (8,10). The benefits of screening for men with BRCA1/2 mutations are not known although recommendations for annual mammography and workup for prostate cancer have been suggested (PSA, DRE) (8,9).
The ISET CSC blood test may provide a more sensitive test for cancer screening in BRCA1/2 patients. Previous reports have found CSC identified by cell surface markers, are associated with metastatic disease and a poor prognosis (12) Recently a new technology for isolation of CSC from blood has used cell size rather than markers to isolate circulating sentinel cells. The analysis of these circulating cells by size rather than expression of cell surface markers significantly changes the way in which ISET CSC’s may be used in patient care. The presence of ISET-isolated circulating sentinel cells (CSCs) is currently thought to be an early finding and is correlated with the growth of the primary sentinel rather than metastasis. These cells are sloughed early during carcinogenesis. In animal models, ISET isolated CSC’s can be isolated from tumors as small as 1mm. Until recently, ISET CSC research has primarily focused on existing tumors, but a recent publication by Marius IIie, et al. has identified “Sentinel” Circulating Sentinel Cells in COPD patients, allowing increased surveillance with annual CT scans and earlier diagnosis of lung cancer in this “at risk” population. Most remarkable is the finding that ISET CSCs were identified 1-4 years prior to detection of cancer by CT scans. They also reported significantly improving survival rates (13). Their study demonstrates the value of CSC detection and enhanced imaging surveillance to aid in an earlier diagnosis of lung cancer. These findings clearly suggest that blood testing for ISET CSCs may provide a very valuable tool in screening high risk patients such as those with BRCA1/2 mutations.
In BRCA1/2 patients found to have ISET CSC, continued blood testing may be helpful in identifying preferred therapeutic options as well as efficacy of treatment protocols. If CSCs can be identified years earlier than the current screening modalities, these BRCA1/2 patients may be motivated to have earlier prophylactic procedures and may therefore have improved survival rates. In contrast, if ISET CRC testing proves to be very sensitive, patients and physicians may be more comfortable delaying prophylactic procedures that are perceived as disfiguring or sterilizing.
Furthermore, once ISET CSC’s are identified, continued testing for ISET CSCs may allow better analysis of the role of chemo-prevention, to reduce the risk of, or delay the recurrence of cancer. Although two chemo-preventive drugs (tamoxifen and raloxifene) have been approved by the U.S. FDA to reduce the risk of breast cancer in women at increased risk, the role of these drugs in women with BRCA1/2 is unclear and might be further elucidated. In addition, there are some data that suggest that fallopian tubes play a dominant role in the associated ovarian cancer. ISET CSC testing may provide a tool for following patients undergoing limited prophylactic procedures such as excision of fallopian tubes while preserving ovaries.