Risk factors and causes
Scientists continue to study the genes responsible for familial ovarian cancer. This research is beginning to yield clues about how these genes normally work and how disrupting their action can lead to cancer. This information eventually is expected to lead to new drugs for preventing and treating familial ovarian cancer.
Research in this area has already led to better ways to detect high-risk genes and assess a woman’s ovarian cancer risk. A better understanding of how genetic and hormonal factors (such as oral contraceptive use) interact may also lead to better ways to prevent ovarian cancer.
New information about how much BRCA1 and BRCA2 gene mutations increase ovarian cancer risk is helping women make practical decisions about prevention. For example, mathematical models have been developed that help estimate how many years of life an average woman with a BRCA mutation might gain by having both ovaries and fallopian tubes removed to prevent a cancer from developing. Studies have shown that fallopian tube cancers develop in women with BRCA gene mutations more often than doctors had previously suspected. However, it is important to remember that although doctors can predict the average outcome of a group of many women, it is still impossible to accurately predict the outcome for any individual woman.
Recent studies suggest that many primary peritoneal cancers and some ovarian cancers (such as high-grade serous carcinomas) actually start in the fallopian tubes. According to this theory, the early changes of these cancers can start in the fallopian tubes. Cells from these very early fallopian tube cancers can become detached and then stick to the surface of the peritoneum or the ovaries. For reasons that are still not understood, these cancer cells may grow more rapidly in their new locations.
This theory has important implications for preventing ovarian cancer because having the ovaries removed early can cause problems from lack of estrogen, such as bone loss, cardiovascular disease, and menopause symptoms. Some experts have suggested recently that some women who are concerned about their ovarian cancer risk (especially those with a strong family history and/or BRCA gene mutations) consider having just their fallopian tubes removed first. They then can have their ovaries removed when they are older. This approach lets women keep their ovaries functioning for longer, but because of that, it might not help breast cancer risk as much. This is an active area of research.
Other studies are testing new drugs for ovarian cancer risk reduction.
Researchers are constantly looking for clues such as lifestyle, diet, and medicines that may alter the risk of ovarian cancer.
Accurate ways to detect ovarian cancer early could have a great impact on the cure rate. Researchers are testing new ways to screen women for ovarian cancer, and a national repository for blood and tissue samples from ovarian cancer patients is being established to aid in these studies. One method being tested is looking at the pattern of proteins in the blood (called proteomics) to find ovarian cancer early.
From time to time, lab companies have marketed unproven tests to look for early ovarian cancer. Because these tests had not yet been shown to help find early cancer, the US Food and Drug Administration (FDA) told the companies to stop selling them. So far, this occurred with 2 different tests looking at protein patterns: OvaSure and OvaCheck. Both were taken off the market at the request of the FDA.
Two large studies of screening have been completed. One was in the United States, and the other was in the United Kingdom. Both studies looked at using the CA-125 blood test along with ovarian (transvaginal) ultrasound to find ovarian cancer. In these studies, more cancers were found in the women who were screened. Some of these were found at an early stage. But the outcomes of the women who were screened were not better than the women who weren’t screened. – the screened women did not live longer and were not less likely to die from ovarian cancer.
A test called OVA1 is meant to be used in women who have an ovarian tumor. It measures the levels of 4 proteins in the blood. The levels of these proteins, when looked at together, are used to put women with tumors into 2 categories − low risk and high risk. The women labeled low risk are not likely to have cancer. The women called “high risk” are more likely to have a cancer, and so should have surgery by a specialist (a gynecologic oncologist). This test is NOT a screening test − it is only meant for use in women who have an ovarian tumor.
Treatment research includes testing the value of currently available methods as well as developing new approaches to treatment.
New chemotherapy (chemo) drugs and drug combinations are being tested. The drugs trabectedin (Yondelis®) and belotecan have shown promise in some studies.
When the drugs cisplatin and carboplatin stop working, the cancer is said to be platinum resistant. Studies are looking for ways (like other drugs) to make these cancers sensitive to these drugs again.
Although carboplatin is preferred over cisplatin in treating ovarian cancer if the drug is to be given IV, cisplatin is used in intraperitoneal (IP) chemotherapy. Studies are looking at giving carboplatin for IP chemo.
Another approach is to give IP chemo during surgery using heated drugs. This, known as heated intraperitoneal chemotherapy or HIPEC, can be effective, but is very toxic. It still needs to be studied and compared with standard IP chemo to see if it actually works better.
Targeted therapy is a newer type of cancer treatment that uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells. Each type of targeted therapy works differently, but they all attack the cancer cells’ inner workings − the programming that makes them different from normal, healthy cells. Bevacizumab (Avastin) is the targeted therapy that has been studied best in ovarian cancer, but other drugs are also being looked at, as well.
Pazopanib (Votrient®) is a targeted therapy drug that, like bevacizumab, helps stop new blood vessels from forming. It has shown some promise in studies.
Poly(ADP-ribose) polymerases (PARPs) are enzymes that have been recently recognized as key regulators of cell survival and cell death. Drugs that inhibit PARP-1 help fight cancers caused by mutations in BRCA1 and BRCA2. In one study, the PARP inhibitor olaparib was also able to shrink tumors in ovarian cancer patients who did not have BRCA mutations. Clinical trials of this type of drug are being done to see who will benefit most from them.
Vintafolide (EC145) is a newer drug that targets the folic acid receptor. This receptor is found on some ovarian cancers. In one study, it helped stop the growth of cancers that had the folic acid receptor.
Another approach is to develop tumor vaccines that program the immune system to better recognize cancer cells. Also, monoclonal antibodies that specifically recognize and attack ovarian cancer cells are being developed. These antibodies are man-made versions of the antibodies our bodies make to fight infection. They can be designed to home in on certain sites on the cancer cell. Farletuzumab is a monoclonal antibody that is directed against the folic acid receptor, which is on the surface of some ovarian cancer cells. It has shown promise in treating ovarian cancer in early studies. Another monoclonal antibody being studied in ovarian cancer is called catumaxomab. It binds to a protein that is in some cancer cells and some immune system cells. When it is administered into the abdominal cavity, it can help treat fluid buildup (ascites) that can occur when cancer is present.