Ovarian cancer

Most cases of ovarian cancer occur sporadically in people with little to no family history of the condition. They are due to random changes (mutations) that occur only in the cells of the ovary. These mutations (called somatic mutations) accumulate during a person's lifetime and are not inherited or passed on to future generations.

However, approximately 10-25% of ovarian cancers are thought to be "hereditary." These cases are caused by an inherited predisposition to ovarian cancer that is passed down through a family. In some of these families, the underlying genetic cause is not known. However, many of these cases are part of a hereditary cancer syndrome. For example, the following cancer syndromes are associated with an elevated risk of ovarian cancer and several other types of cancer:

• Hereditary breast and ovarian cancer syndrome due to mutations in the BRCA1 or BRCA2 gene is the most common known cause of hereditary ovarian cancer.
• Lynch syndrome is caused by mutations in the MLH1 , MSH2, MSH6, PMS2 or EPCAM gene
• Peutz-Jeghers syndrome is caused by mutations in the STK11 gene

Of note, some research suggests that inherited mutations in several other genes (including BARD1 ,BRIP1, MRE11A, NBN, RAD51, RAD50, CHEK2, _and PALB2_) may also be associated with an increased risk for ovarian cancer. However, the risk associated with many of these genes is not well understood. Most are termed "moderate- or low- penetrant" genes which means that, on their own, they would be expected to have a relatively small effect on ovarian cancer risk. However, in combination with other genes and/or environmental factors, these genes may lead to a significant risk of ovarian cancer.

If ovarian cancer is suspected based on the presence of certain signs and symptoms, the following tests and procedures may be recommended:

• Physical evaluation and pelvic exam to check for signs of ovarian cancer (i.e. lumps or swelling) and to examine the size, shape and location of the ovaries
• Ultrasound and other imaging studies to look for abnormal growths
• Blood tests such as a CA-125 assay which may be elevated in people with ovarian cancer
• A biopsy of the tumor is the only way to confirm a diagnosis of ovarian cancer

The National Cancer Institute offers more detailed information regarding the tests used to diagnose ovarian cancer. To access this resource, please click here.

Most cases of ovarian cancer occur sporadically in people with little to no family history of the condition. However, approximately 10-25% of ovarian cancer is thought to be inherited. In some of these families, the underlying genetic cause is not known. However, many of these cases are part of a hereditary cancer syndrome such as BRCA1 or BRCA2 hereditary breast and ovarian cancer syndrome, Lynch syndrome and Peutz-Jeghers syndrome, which are inherited in an autosomal dominant manner. This means that a person only needs a change (mutation) in one copy of the responsible gene in each cell to have a hereditary predisposition to ovarian cancer and other cancers associated with these syndromes. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. A person with one of these syndromes has a 50% chance with each pregnancy of passing along the altered gene to his or her child.

The long-term outlook (prognosis) for women with ovarian cancer depends on many factors including the subtype of cancer and the stage at which the cancer is diagnosed. In general, epithelial ovarian cancers (the most common subtype) are often associated with a worse prognosis than more rare subtypes such as germ cell and stromal ovarian tumors.

Because early stages of ovarian cancer are often not associated with any specific signs or symptoms, many cases are, unfortunately, diagnosed at a later and less treatable stage. Late stage ovarian cancers are generally associated with a poor prognosis. For example, 5-year survival rates for women diagnosed with stage I ovarian cancer range from 79-87%, while the 5-year survival rates for women diagnosed with stage IV ovarian cancer are approximately 11%.

The best treatment options for ovarian cancer depend on many factors including the subtype and stage of the condition. In general, treatment may include a combination of the following:

• Surgery to remove the ovaries, the fallopian tubes, the uterus, and/or other structures in the belly (pelvis).
• Chemotherapy
• Radiation therapy
• Targeted therapy (such as monoclonal antibody therapy)

Unfortunately, research suggests that there are no benefits of ovarian cancer screening (using a CA-125 blood test and transvaginal ultrasound), even in women who are at an elevated risk due to their personal and/or family histories. Women who are at a high-risk for ovarian cancer may, therefore, want to discuss other preventative measures, such as prophylactic surgery, with their healthcare provider. In women with a known hereditary cancer syndrome, management should also include screening for the other component cancers. Please click on the following links for more information regarding the treatment and management of each condition:

• Hereditary Breast and Ovarian Cancer
• Lynch syndrome
• Peutz-Jeghers syndrome