NORD gratefully acknowledges Ronny I. Drapkin, MD, PhD, Associate Professor, Obstetrics, Gynecology and Pathology; Director, Ovarian Cancer Research Center, University of Pennsylvania; Director, Gynecologic Cancer Research, Basser Research Center for BRCA, for assistance in the preparation of this report.
Ovarian cancer refers to cancer that arises in the almond-shaped reproductive organs in women in which eggs, or ova, are produced (ovaries), in either of the two tubes through which eggs travel from the ovaries to the uterus (fallopian tubes), or in the membrane that lines the pelvis and the abdominal cavity and covers all of the abdominal organs (peritoneum). There are usually no symptoms (asymptomatic) during the early stages. As a result, ovarian cancer is usually not diagnosed until an advanced stage. Common symptoms that can develop include abdominal swelling or bloating, unintended weight loss, or changes in the bowel habits including constipation. The cause of ovarian cancer is multifactorial, which means that multiple factors that occur together are necessary for the cancer to develop. These factors include genetic, immunologic and environmental factors. About 20% of all women with ovarian cancer have a variation in one of two genes called BRCA1 or BRCA2. BRCA-associated ovarian cancer is not specifically discussed in this report. NORD has a separate report on ovarian cancer caused by variations in these two genes that is titled Hereditary Breast and Ovarian Cancer (HBOC) Syndrome.
Ovarian cancer is a nonspecific term for a group of tumors. However, more than 90% of ovarian cancer arises from epithelial cells; these cells cover most internal and external surfaces of the body and its organs. Epithelial cancer of the ovaries, fallopian tubes, and peritoneum share similar behavior and characteristics. These closely related cancers are often grouped together and can be referred to as epithelial ovarian cancer or EOC. This report primarily deals with epithelial ovarian cancer (carcinoma). Most instances of EOC are high grade serous carcinoma. Most high grade serous carcinomas are now believed to originate in the very tips of the fallopian tubes. Additional subtypes of EOC are low-grade serous carcinoma, mucinous, clear cell, endometroid, and undifferentiated, in which the cancer cells are very immature and do not look like the cells in the tissue in which the cancer begins.
Other types of ovarian cancer include stromal tumors, in which cancer arises in the ovarian tissue that contains hormone-producing cells, and germ cell tumors, in which cancer arises in the egg-producing cells. Stromal tumors are also called sex cord-stromal tumors and make up about 7% of women with ovarian cancer. Types of stromal tumor include granulosa, granulosa-theca, and Sertoli-Leydig cell. Germ cell tumors are extremely rare and occur in younger women (about 80% in women under 30 years of age). Types of germ cell tumors include teratoma, dysgerminoma, endodermal sinus tumor, and choriocarcinoma.
The specific symptoms and physical findings of ovarian cancer can vary from one person to another, depending upon the extent and region(s) of involvement and other factors. Ovarian cancer usually does not cause any symptoms in the early stages. Symptoms may be described as acute (developing rapidly and severely) or subacute (having a slower onset and slower progression).
Affected individuals can develop abdominal bloating, the need to urinate quickly and frequently, changes in bowel habits including constipation, difficulty eating and a sense of feeling full quickly, unintended weight loss, and pelvic or abdominal pain or discomfort. Some women may have ascites, a condition characterized by the buildup of fluid in the abdomen. Additional symptoms that can develop including fatigue, back pain, an upset stomach, pain during sex, and changes to the menstrual cycle. Some women have an adnexal mass. An adnexal mass of the uterus is found in any area nearby the uterus that is related structurally or functionally. This includes the ovaries, fallopian tubes, and other nearby tissue. An adnexal mass can sometimes be the first sign of ovarian cancer and can cause a sense of pressure or pain in the pelvic region.
Some women develop more severe symptoms of ovarian cancer. This usually occurs when the cancer is at an advanced stage. Such symptoms include fluid buildup around the lungs (pleural effusion) and obstruction or blockage of the digestive tract (bowel obstruction). The pleura are thin membranes that line the lungs. A small amount of fluid allows the lungs to move within the chest cavity. When excess fluid builds up in this space, the lungs cannot move easily or properly. Pleural effusion can cause shortness of breath, a cough, or chest pain.
Bowel obstruction refers to the inability of the body to propel waste through the intestines. This can cause crampy abdominal pain, loss of appetite, swelling of the abdomen, and constipation. Severe nausea and vomiting can also occur.
The exact, underlying cause of ovarian cancer is not fully understood. The reason why cancer develops is a complex question and researchers speculate that multiple factors are involved in the development of ovarian cancer. These factors can include genetic, environmental and immunologic factors.
People with certain genetic disorders are more likely to develop ovarian cancer. The most common underlying cause of ovarian cancer is variations in either the BRCA1 or BRCA2 genes. This is part of the hereditary breast and ovarian cancer (HBOC) syndrome, which is an inherited cancer-predisposition syndrome. Affected individuals have a significantly greater risk of developing certain cancers, particularly breast cancer, in both men and women, and ovarian cancer in women. Affected individuals tend to develop cancer earlier in life as well, usually before the age of 50. BRCA-associated ovarian cancer is a specific, genetic condition that differs from ovarian cancer due to other causes, although the cancer may appear similar when viewed under a microscope.
Several other genes have been identified that may play a role in the development of ovarian cancer. These genes include the BRIP1, RAD51C, and RAD51D genes as well as the mismatch repair (MMR) genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain. Variations (mutations) in genes associated with ovarian cancer have been shown to increase a person’s risk of developing cancer (genetic predisposition). A genetic predisposition means that a person has a gene or genes for a disease, but the disease will not develop unless additional genetic or environmental factors are also present. Other subtypes of ovarian cancer may be associated with other gene variations. For example, low-grade serous carcinoma is associated with variations in the BRAF and RAS genes. Certain genes, such as a variation in the FABP4 gene, may play a role in whether ovarian cancer is more likely to spread (metastasize) to other areas of the body. Understanding the underlying genetic factors in cancer can lead to better, more targeted therapies.
Lynch syndrome is another hereditary cancer syndrome in which affected women are more likely to develop ovarian cancer. Variations in several genes are known to cause Lynch syndrome including MLH1, MSH2, MSH6, PMS2, and EPCAM. Lynch syndrome is also known as hereditary nonpolyposis colorectal cancer (HNPCC).
Additional risk factors for ovarian cancer include infertility, long-term postmenopausal hormone therapy (estrogen replacement therapy), the use of an intrauterine device, increasing age, having never given birth to a child (nulliparity), endometriosis, and polycystic ovarian syndrome (PCOS). Endometriosis is a common condition in which the tissue that lines the uterus (endometrium) grows outside of the uterus, most often affecting the ovaries, fallopian tubes or the tissue lining the pelvis. Pain is the most common symptom of endometriosis. Endometriosis is specifically associated with an increased risk of endometrioid and clear cell ovarian cancer, but not high-grade serous carcinoma or mucinous tumors. PCOS can result in irregular menstrual periods or a lack of menstruation, oily skin that is prone to acne, cysts on the ovaries and mild hirsutism (a male pattern of hair growth). Hair may develop on the upper lip and chin. PCOS may occur as a symptom of insulin resistance. Some women enter puberty early (before the age of 8), a condition called precocious puberty.
Cigarette smoking is modifiable risk factor that is associated with an increased risk of a mucinous carcinoma of the ovary.
There is a theory that continuous (incessant) ovulation is a risk factor for ovarian cancer. Many things can impact ovulation, which is when a woman releases an egg during menstruation. When a woman first begins having a period and when she reaches menopause, including early onset of a woman’s period (early menarche) or late menopause, are both related to the frequency of ovulation. Prolonged use of oral contraceptives (i.e. 5 or more years) may decrease a woman’s risk of developing ovarian cancer.
In 2017, more than 22,400 women were diagnosed with ovarian cancer in the United States. It affects about 1 in 70 women in the U.S and is the second most common gynecological cancer behind only endometrial cancer. The average age at diagnosis is 63. Worldwide about 240,000 women are diagnosed each year with ovarian cancer. The incidence, which is the number of people with a disease over a given period of time such as one year, is greater in developed countries.
A diagnosis of ovarian cancer is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. There is no screening test that can be run that detects ovarian cancer in all women. Ovarian cancer does not cause many symptoms during the early stages of development, and symptoms tend to be nonspecific (common to many diseases). Consequently, ovarian cancer is often undiagnosed until it has spread to the abdomen and pelvis.
Clinical Testing and Workup
A pelvic exam is an examination where a physician evaluates a woman’s reproductive organs. A physician will insert gloved fingers into the vagina while pressing down on the abdomen. This allows a physician to feel the pelvic organs. A physician will also visually inspect a woman’s external reproductive organs. Most times, a pelvic exam does not diagnose ovarian cancer. When it does, it is usually because a physician noted an abnormally enlarged ovary.
Blood tests may be ordered to test for markers of ovarian cancer. A marker is a substance that when present is indicative of a disease. If there are increased levels of cancer antigen 125 (CA-125), then this is indicative of ovarian cancer. CA-125 is a protein that is produced by ovarian cancer cells. However, other disorders, including non-cancerous conditions, can also lead to increased levels of CA-125 so this test does not conclusively diagnose ovarian cancer because other conditions must still be ruled out. HE4 (human epididymis protein 4) is another biomarker that is elevated in the blood serum of some women with ovarian cancer. HE4 can be elevated in the blood because of other types of cancer and is not diagnostic of ovarian cancer on its own. HE4 is more specific than CA-125, and some studies suggest that testing for both markers is more accurate.
Specialized imaging techniques may be used to aid in a diagnosis. Such tests include transvaginal sonography, computerized tomography (CT) scanning and magnetic resonance imaging (MRI). A transvaginal sonography is a special type of ultrasound examination. Ultrasounds use high-frequency radio waves to create a picture or image (sonogram) of specific structures like internal organs. The radio waves bounce off of internal structures within the body and the echoes are recorded to create a sonogram. A transvaginal sonography is a type of ultrasound that is used to look at the vagina, uterus, ovaries and fallopian tubes. During this exam, an ultrasound wand is inserted into the vagina to allow the physician to create pictures of the organs of the pelvic region.
A CT scan or MRI is more likely to be used when advanced stage ovarian cancer is present. During CT scanning, a computer and a low-dose of x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. A CT scan or MRI may be used to determine the exact location, define the boundaries of a tumor, or determine the extent or spread of cancer. They are usually recommended after initial tests indicate ovarian cancer. They can be used to help a physician plan treatment and assess the success of treatment.
The main diagnostic procedure for ovarian cancer is the surgical removal of a small amount of tissue from the ovaries, fallopian tubes or peritoneal tissue, which is then studied under a microscope (biopsy). The tissue sample is studied by a doctor who specializes in examining tissue and cells and determining what disease is present (pathologist). Some physicians caution that women with suspected ovarian cancer, but with no signs of the disease (i.e. early stage disease), will benefit from the complete removal of an adnexal mass rather than taking a small sample. Any cutting or rupturing of a cancerous tumor runs a risk of spreading cancer cells and leading to more advanced disease.
In addition, in some instances, such as when involvement appears to include the abdominal or pelvic region, laparoscopy or laparotomy may be necessary to obtain biopsy samples. Laparoscopy involves examination of the abdominal cavity with an illuminated viewing tube (laparoscope) inserted through incisions in the abdominal wall. Laparotomy is a surgical procedure in which the abdomen is opened, organs are carefully examined to detect signs of disease, and samples of tissue are removed for microscopic examination. Sometimes, fluid samples are taken and studied. This can include fluid from the abdomen when ascites is present or fluid from the lungs when pleural effusion is present.
When an individual is diagnosed with ovarian cancer, assessment is also required to determine the extent or “stage” of the disease. Staging is important to help characterize the potential disease course and determine appropriate treatment approaches. A variety of diagnostic tests may be used in staging ovarian cancer (e.g., blood tests, CT scanning, laparoscopic biopsy). Epithelial ovarian carcinoma is staged based on one of two staging systems – the 2017 International Federation of Gynecology and Obstetrics (FIGO) classification system, and the Tumor, Node, Metastasis (TNM) classification system. These staging systems are available at: https://emedicine.medscape.com/article/2007140-overview
The therapeutic management may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who use radiation to treat cancer (radiation oncologists), physicians who specialize in diagnosing and treating disorders of women, especially of the reproductive tract (gynecologists), a physician who specializes in diagnosing and treating cancer that involves a woman’s reproductive organs (gynecological oncologists), pathologist, oncology nurses, clinical nurse specialist, psychiatrists, and other healthcare specialists.
Psychosocial support for the entire family is essential as well. Several of the organizations listed in the Resources section provide support and information on cancer.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; specific ovarian cancer subtype; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case. A thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors should also be had with the patient.
Surgery and chemotherapy are the two most common treatment options. Surgery is usually the initial therapy and the exact surgical procedure depends on the location and extent of the cancer as well as the stage of the cancer.
If ovarian cancer is contained to one ovary, then a surgeon can remove the affected ovary. This will preserve fertility in women of child-bearing age. Preserving fertility is attempted most often with young women with tumors of low malignant potential, or non-epithelial ovarian cancers.
If cancer present in both ovaries, a surgeon will remove both ovaries and fallopian tubes. Doctors may recommend removing the uterus (hysterectomy) along with the ovaries and the fallopian tubes (salpino-oophorectomy). Sometimes, a thin fold of tissue in the abdomen called the omentum is also removed. In younger patients, surgeons may perform a unilateral salpino-oophorectomy to preserve fertility. These surgeries may be recommended in women after counseling on reproductive issues, degree of protection, and hormonal and menopausal issues. Surgery may be necessary to remove other areas potentially affected by ovarian cancer such as the spleen and segments of the bowels.
If the cancer has spread to other areas, surgery will be performed to remove as much of the cancer as possible. This is called debulking surgery, or cytoreduction. Following this surgery, a patient will receive chemotherapy. Many different chemotherapy drugs and regimens can be used. Occasionally, chemotherapy can also be given before surgery. This treatment, called neo-adjuvant chemotherapy, helps shrink the tumor and make it easier to remove.
The chemotherapy regimen for ovarian cancer is fairly standard. Treating physicians combine a DNA-damaging agent like Cisplatin or Carboplatin with another drug, called Paclitaxel that prevents cells from dividing properly. Like all medications, platinum-based chemotherapy is associated with side effects. This combination is effective in many women but resistance to these drugs can emerge.
PARP inhibitors are an exciting new class of therapy for ovarian cancer. PARP is an enzyme that helps the body to repair DNA when it becomes damaged, especially in cells that have a mutation in the BRCA genes. Researchers believe that medications that stop or hinder (inhibit) the activity of PARP will prevent cancer cells from repairing themselves, and continuing to grow and spread. This is a targeted therapy, which means that it is targeting a specific molecule or substance (e.g. PARP) that contributes to cancer growth. Targeted therapies act by blocking the growth and spread of cancer rather than destroying cancer cells (cytotoxic treatments) like chemotherapy or radiation therapy and are less likely to damage healthy cells.
There are currently three PARP inhibitors that are approved by the U.S. Food and Drug Administration (FDA) to treat ovarian cancer. Olaparib (Lynparza®) is approved for maintenance therapy in women with ovarian cancer, or women who have ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have responded to treatment with a platinum-based chemotherapy medication, but in whom the cancer has returned. Lynparza is also approved for advanced ovarian cancer in women who have received treatment with three or more prior chemotherapy medications. Lynparza is an inhibitor of PARP, or poly (ADP-ribose) polymerase.
Rucaparib (RuBRCAa®) is a PARP inhibitor that approved for the treatment of recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer in individuals who are in a complete or partial response to treatment with a platinum-based chemotherapy medication.
Bevacizumab (Avastin) is a PARP inhibitor that is approved for use with carboplatin and paclitaxel, followed by bevacizumab alone (monotherapy) for the treatment of women with advanced ovarian cancer following initial surgical removal of cancer. Avastin is a tumor starving therapy that works by preventing the growth of new blood vessels that can feed the tumor. Bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan is FDA approved for women with platinum-resistance recurrent ovarian cancer.
Niraparib (Zejula®) is FDA approved for the treatment of recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer in individuals who are in a complete or partial response to treatment with a platinum-based chemotherapy medication.
Gemcitabine (Gemzar®) is approved to treat women with advanced ovarian cancer that has relapsed at least six months after initial therapy.
Emerging studies suggest that combining PARP inhibitor with other therapies, including immunotherapies, may be effective in patients with recurrent ovarian cancer.
Radiation therapy is rarely used for ovarian cancer unless the cancer has spread to other areas of the body.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
There is a Familial Ovarian Cancer Registry based out of the Roswell Park Cancer Institute in Buffalo, NY. A registry is a special database that contains information about individuals with a specific disorder or group of conditions. The collection of data about rare disorders may enable researchers to increase the understanding of such disorders, expand the search for treatments, and accelerate clinical trials into specific treatment options. The Registry is seeking to identify all of the genes that predispose women to ovarian cancer. For more information, visit: http://ovariancancer.com/
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