WHAT IS BRCA PROJECT?
The BRCA Project is a non-profit organization committed to furthering translational medicine treating patients with genetic risk for breast cancer.
“BRCA1 and BRCA2 genes are passed down from generation to generation.”
Analysis of the Diagnostic Value of Sentinel Tumor Cells (STC) using Isolation by SizE of Tumor cell (ISET) method for Early Cancer Detection and Efficacy of Treatment in Patients with BRCA1/2 mutations.
The BRCA Project is committed to studying the effects of early detection and diagnoses of breast cancers in high-risk patients and BRCA.
Our current study:
Includes 100 Female and 100 Male patients at high risk for breast cancer.
You are invited to participate in the BRCA Project because you have had breast cancer and/or are at increased risk for breast and related cancers, OR because you are a good control subject for the patients in this study.
YOUR PARTICIPATION IS VOLUNTARY
Your participation is entirely voluntary, so it is up to you to decide whether or not to take part in this study. Before you decide, it is important for you to understand what the research involves. This consent form will tell you about the study, why the research is being done, what will happen to you during the study and the possible benefits, risks, and discomforts that might be associated with the study.
If you wish to participate you will be asked to sign this form. If you decide to take part in this study, you are free to withdraw at any time and without giving any reasons for your decision.
If you do not wish to participate, you do not have to provide any reason for your decision not to participate, nor will you lose the benefit of any medical care to which you are entitled or are presently receiving.
This is a self-funded study. Meaning there are not independent companies who can manipulate the outcome.
WHO IS CONDUCTING THE STUDY?
The Principle Investigator, Dr. Barbara Hayden, is conducting the study. The Principal Investigator does not have any actual or potential conflicts of interest and will not receive financial compensation for enrolling subjects into this study.
Who are the Male and Female Patients At Risk?
Breast Cancer is the most common malignancy in women in Europe and the United States and it is the second leading cause of cancer-related deaths. Women are not the only people at risk. Both Male and Female patients with significant family histories and/or known genetic risks, such as the BRCA genes, have significant lifetime risks not only for breast cancers but also for other cancers. The BRCA1 gene is more significant in women, posing a greater lifetime risk for breast cancer, but BRCA2 is more significant in men. Studies report the overall cancer risk to male BRCA2 carriers exceeds the risk for female carriers. Specifically, the relative risk to male BRCA2 mutation carriers is high before age 65 years and is attributable to breast, prostate, and pancreatic cancers. BRCA2 carriers are also at risk for developing stomach cancer and melanoma (of the skin and eye). The risk is so significant that population-based screening for BRCA1 and BRCA2 is advocated by leading scientists such as Mary-Claire King, et al. in the 2014 Lasker award-winning paper in JAMA. The association between BRCA1/2 genes and cancer has been well defined and extensively studied, but many patients without the BRCA mutation, with strong family histories of breast cancer, are also likely to have an increased risk of breast cancer and also merit study.
What are the Current Cancer Screening Protocols?
The National Cancer Institute recommends that patients identified as carriers of BRCA1 and BRCA2, and those with strong family histories undergo “enhanced screening, prophylactic surgery, and chemoprevention”. Enhanced screening includes earlier breast examinations, mammograms and MRI for breast cancers starting at age 25. The NCI states that no effective ovarian cancer screening methods currently exist. Some groups recommend transvaginal 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. 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 (Blood teasing for PSA, Digital Rectal Exam).
What is the ISET Blood Test?
ISET is short for Isolation by SizE Technique. The ISET blood test looks for rare cells that are circulating in the blood. These cells are harvested from your blood with a simple blood test, however, the cells are processed within hours and filtered by size to select for cells that are not typically in your blood.
Once harvested, filtered and processed, these rare cells are examined by specialized pathologists to determine if there are unusual characteristics that are suggestive of cancer cells. This test is very similar to a PAP Smear or needle biopsy in that the diagnosis of these rare cells is determined by a pathologist. Unlike a PAP smear, this test has not yet completed clearance by the FDA as a diagnostic test for cancer.
WHAT IS THE PURPOSE OF THIS STUDY?
The ISET blood test is currently being studied at several U.S. Universities and Research Institutions and in Europe. To date, there is 40 peer reviewed articles that demonstrate its usefulness. It has been established as useful n prenatal diagnosis of genetic disorders. It has been used as a tool for early diagnosis in patients at risk for lung cancer. However, more data is needed to garner FDA approval of this new blood test as a predictable tool for early diagnosis of cancers and efficacy of treatment in existing cancers
The presence of ISE-Technique identified Rare Cells that appear abnormal or have features of cancer is determined by the pathologist and is based on cellular features. Sometimes additional testing of the cells may be needed to identify the source of the cells (which organ they are from). Some unusual findings may indicate the need for further studies of DNA or RNA that might identify the source and malignant potential of the cells. Though this will not be done routinely, the investigators reserve the right to proceed with these DNA/RNA and Genome studies as appropriate and use the data to advance cancer therapy.
Why is ISET useful in patients who have not had cancer?
When these cells are found in someone who has not previously had cancer, this is likely to be an early finding based on current data. Cell counts of these rare cells can be correlated with the growth of the primary tumor years before metastasis. The current data suggest the malignant appearing cells are not metastases, but rather are incidentally discarded into the bloodstream long before the cancer cells acquire the ability to re-attach and grow somewhere else.
In animal models, ISET isolated cells can be isolated from blood even when tumors are as small as 1mm. A recent publication by Marius IIie, et al. has identified “Sentinel” Circulating Tumor Cells (CTC) 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 circulating tumor cells were identified 1-4 years before detection of cancer by other means including CT scans. Marius, IIie, et al. have reported significantly improved survival rates, converting an 80% mortality rate to an 80% survival rate in high-risk patients who did develop lung cancer. Their study demonstrates the value of CTC detection and enhanced imaging surveillance to aid in an earlier diagnosis of lung cancer. These findings clearly suggest that blood testing for ISET CTCs may provide a very valuable tool in screening patients at greater risk for cancer.
In BRCA1/2 patients found to have ISET Circulating Tumor Cells, continued blood testing may be helpful in identifying preferred therapeutic options as well as the efficacy of treatment protocols.
If ISET identified Circulating Tumor Cells could 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. Alternatively, 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.
The analysis of ISET Circulating Tumor Cells may allow safer evaluation of chemoprevention options to reduce the risk of, or delay the recurrence of cancer. Although two chemopreventive 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. Also, there are some data that suggest that fallopian tubes play a dominant role in the associated ovarian cancer. ISET testing may provide a tool for following patients undergoing limited prophylactic procedures such as excision of fallopian tubes while preserving ovaries, thus minimizing their risk of missing an early ovarian cancer.
WHO CAN PARTICIPATE?
Patients who are BRCA 1/2
Patients with other identified increase risk for Breast and Ovarian Cancers
Patients with biopsy proven Breast Cancer
Control Patients without a personal or family history of breast or ovarian cancer
WHO SHOULD NOT PARTICIPATE IN THIS STUDY?
Patients who do not feel they can give an informed consent
Patients who suffer from anxiety, depression, or other psychological or psychiatric conditions
Patients who are currently without medical care or a physician
WHAT DOES THE STUDY INVOLVE?
This study is comparable to a simple blood test. Approximately 20 cc’s of blood is withdrawn for processing and analysis. The test is performed annually. You will be reminding of your return date.
WHAT ARE MY RESPONSIBILITIES?
This is an observational study and does not require your direct participation other than the release of your information for research purposes.
WHAT ARE THE POSSIBLE HARMS AND SIDE EFFECTS OF PARTICIPATING?
There can be bruising or bleeding. Some patients may experience anxiety over the results. Since this is an experimental study that has not been approved by the FDA the results cannot be provided to the patient.
WHAT ARE THE BENEFITS OF PARTICIPATING IN THIS STUDY?
No one knows whether or not you will benefit from this study. There may or may not be direct benefits to you from taking part in this study. We hope that the information learned from this study can be used in the future to benefit all patients at risk for cancer.
WHAT ARE THE ALTERNATIVES TO THE STUDY TREATMENT?
This study does not provide a treatment. Alternative screening options are described in section 4
WHAT HAPPENS IF I DECIDE TO WITHDRAW MY CONSENT TO PARTICIPATE?
Your participation in this research is entirely voluntary. You may withdraw from this study anytime. If you decide to enter the study and then withdraw at any time in the future, there will be no penalty or loss of benefits to which you are otherwise entitled and your future medical care will not be affected.
WHAT HAPPENS IF SOMETHING GOES WRONG?
Signing this consent in no way limits your legal rights against the investigators or anyone else.
Subjects will not be paid for this study.
WILL MY TAKING PART IN THIS STUDY BE KEPT CONFIDENTIAL?
Your confidentiality will be respected. No information that discloses your identity will be released or published without your specific consent. However, research records and medical records identifying you may be inspected in the presence of the investigator or her designated by representatives of the FDA or IRB governing bodies for the purpose of monitoring compliance with government regulations. No records which identify you by name or initials will be allowed to leave the investigators’ locked offices.