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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.

Prevention

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.

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.

Early detection

Being able to find ovarian cancer early could have a great impact on the cure rate. Researchers are testing new ways to screen women for ovarian cancer. One method being tested is looking at the pattern of proteins in the blood (called proteomics) to find ovarian cancer early.

Imaging

The use of new imaging techniques such as Functional MRI are being evaluated in ovarian cancers. PET/CT scans are also being studied to see where they may be best used for ovarian cancer.

Diagnosis

For women who have an ovarian tumor, a test called OVA1 can measure the levels of 5 proteins in the blood. The levels of these proteins, when looked at together, are used to determine whether a woman's tumor should be considered low risk or high risk. If the tumor is labeled "low risk" based on this test, the woman is not likely to have cancer. If the tumor is considered "high risk," the woman is more likely to have a cancer, and should see a specialist (a gynecologic oncologist). This test is NOT a screening test and it is NOT a test to decide if you should have surgery or not. It is meant for women who have an ovarian tumor where surgery has been decided but have not yet been referred to a gynecologic oncologist.

Treatment

Treatment research includes testing the value of currently available methods as well as developing new approaches to treatment.

Chemotherapy

New chemotherapy (chemo) drugs and drug combinations are being tested.

When the drugs cisplatin and carboplatin stop working, the cancer is said to be platinum resistant. Studies are looking for many ways to make these cancers sensitive to these drugs again. Different strategies include:

• Looking closely at what specific mechanisms and proteins are involved in the making ovarian cancer cells resistant.
• Developing drugs that can keep the cancer cells from becoming resistant to the chemo by blocking channels that pump chemotherapy out of the cancer cell.
• Trying to determine the details of certain cancer cells where the DNA is not damaged by chemotherapy which allows it to keep growing.

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. More studies are showing this to be beneficial and may improve how long a woman lives.

Targeted therapy

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 similar drugs, like pembrolizumab, are being looked at, as well.

Catumaxomab is a drug being studied specifically for people with malignant ascites (fluid buildup in the abdomen [belly] caused by cancer cells). It works by targeting 3 different cell types including tumor cells and white blood cells called T-cells.

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 (called PARP inhibitors) have been approved for patients with ovarian cancer caused by mutations in BRCA1 and BRCA2. New evidence shows that ovarian cancers can also become resistant to treatment with PARP inhibitors. Research is trying to find ways to counteract this process.

Genetic therapies

For ovarian and breast cancers that are caused by the BRCA 1 mutation, it has been shown that low levels of the BRCA 1 mutation are associated with good responses to PARP inhibitors and platinum drugs, like cisplatin and carboplatin. New research shows that microRNA, very small pieces of RNA (substances that carry genetic messages for DNA), can also lower levels of BRCA1 mutations. New drugs that can target these tiny pieces of RNA are being investigated as possible ways to treat these cancers.