Origins and Causes of Ovarian Cancer
While the causes of ovarian cancer are still unknown, scientists have some theories:
Genetic errors may occur during one’s life known as acquired (somatic) gene mutations;
A person can be born with gene mutations (hereditary gene mutations also known as germline mutations);
Because being pregnant and taking birth control pills can lower risk of ovarian cancer, ovarian cancer may be related to ovulation;
Though thought of as male hormones, androgens are found in women at lower levels, and may play a role in ovarian cancer;
And because tubal litigation and hysterectomy seem to lower risk, others have hypothesized that external substances that can cause cancer may enter the body through the vagina and pass through the uterus and fallopian tubes to the ovaries.
Additionally, based on research, it is believed that many if not almost all high-grade serous ovarian cancers (the most common subtype) previously thought to originate in the ovaries actually arise from precursor lesions that begin in the fallopian tubes. Primary Peritoneal Carcinoma (PPC) is thought to develop from cells in the lining of the abdomen and pelvis, called the peritoneum. These cells are very similar to cells on the surface of the ovaries—some researchers believe PPC may also begin in the cells lining the fallopian tubes. Other subtypes diagnosed as PPC share molecular similarities, as well, and therefore high-grade serous carcinomas that originate from the fallopian tube and elsewhere in the peritoneal cavity, together with most epithelial cancers, are staged and treated similarly. Since 2000, FTC and PPC have generally been included in ovarian cancer clinical trials. Regardless of the site of origin, the hallmark of these cancers is their early peritoneal spread or metastases.
Types of Ovarian Cancers
The ovaries are a pair of organs in the female reproductive system. They are in the pelvis, one on each side of the uterus (the hollow, pear-shaped organ where a fetus grows). Each ovary is about the size and shape of an almond. The ovaries make eggs and female hormones. The fallopian tubes are a pair of tubes through which eggs travel from the ovaries to the uterus. The peritoneum is the membrane lining the cavity of the abdomen and covering the abdominal organs.
Ovarian cancers are now known to be several distinct diseases, which are named after the type of cell they come from: epithelial, germ cell, and stromal. These are the three main cell types that make up the ovary. Each cell type can develop into a different type of tumor, and each type differs in how it spreads, how it’s treated and its prognosis.
Epithelial ovarian cancer, which arise from the surface of the ovary (the epithelium), is the most common ovarian cancer. Fallopian Tube Cancer and Primary Peritoneal Cancer are also included within this designation.
Germ Cell ovarian cancer arises from the reproductive cells of the ovaries, and is rare.
Stromal cell ovarian cancer, which arises from connective tissue cells, is very rare.
Small cell carcinoma (SCCO) of the ovary is an extremely rare ovarian cancer and it is not certain whether the cells in SCCO are from ovarian epithelial cells, sex-cord stromal cells or germ cells.
Not all ovarian tumors are cancer. Some ovarian tumors may be abnormal but not necessarily cancerous.
In the United States, doctors must report any diagnosis of cancer to a state registry. The federal government, through the Centers for Disease Control and Prevention’s National Program of Cancer Registries, oversees the registries in 45 states, the District of Columbia and three territories. The Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute funds the remaining five statewide cancer registries. Together, the two programs cover the country’s population.
The following statistics come primarily from the most recent findings of the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute. SEER numbers are age-adjusted and based on actual data.
SEER data is available for most data through 2014. More recent statistics are projections from the American Cancer Society. The American Cancer Society estimates that in 2018, about 22,240 new cases of ovarian cancer will be diagnosed and 14,070 women will die of ovarian cancer in the United States. Mortality rates for ovarian cancer have declined only slightly in the forty years since the “War on Cancer” was declared. However, other cancers have shown a much greater reduction in mortality, due to many factors. The Surveillance, Epidemiology and End Results (SEER) Program reports that in 2014 in the United States approximately 222,060 women were alive who had been diagnosed with ovarian cancer (including those who had been cured of the disease).
Ovarian cancer accounts for 2.5 percent of cancers in women.
While the 11th most common cancer among women, ovarian cancer is the fifth leading cause of cancer-related death among women, and is the deadliest of gynecologic cancers. Mortality rates are slightly higher for Caucasian women than for African-American women.
A Woman’s Lifetime Risk
A woman’s lifetime risk of developing invasive ovarian cancer is 1 in 78. A woman’s lifetime risk of dying from invasive ovarian cancer is 1 in 109.
Age of Ovarian Cancer Diagnosis
Ovarian cancer rates are highest in women aged 55-64 years. The median age at which women are diagnosed is 63, meaning that half of women are younger than 63 when diagnosed with ovarian cancer and half are older.
The median age of death from ovarian cancer is 70. Ovarian cancer survival rates are much lower than other cancers that affect women. Five-year survival rates are commonly used to compare different cancers. The relative five-year survival rate for ovarian cancer is 46.5 percent. Survival rates vary greatly depending on the stage of diagnosis. Women diagnosed at an early stage—before the cancer has spread—have a much higher five-year survival rate than those diagnosed at a later stage. Approximately 15 percent (14.8 percent) of ovarian cancer patients are diagnosed early with early stage disease.
Research has shown that certain risk factors increase the likelihood a woman may get ovarian cancer. Other factors may actually decrease a woman’s probability of getting the disease. Having risk factors does not predict you will get ovarian cancer. Some women who get the disease have no known risk factors, and most women with the risk factors will not get ovarian cancer. However, if you think you may be at risk for ovarian cancer, you should speak with your doctor.
Factors that may increase the risk of ovarian cancer:
Genetics: BRCA1 and BRCA2
About 20 to 25 percent of women diagnosed with ovarian cancer have a hereditary tendency to develop the disease. The most significant risk factor for ovarian cancer is an inherited genetic mutation in one of two genes: breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2). These genes are responsible for about 10 to 15 percent of all ovarian cancers.
Eastern European women and women of Ashkenazi Jewish descent are at a higher risk of carrying BRCA1 and BRCA2 mutations.
Since these genes are linked to both breast and ovarian cancer, women who have had breast cancer have an increased risk of ovarian cancer.
Genetics: Lynch Syndrome
Another known genetic link to ovarian cancer is an inherited syndrome called hereditary nonpolyposis colorectal cancer (HNPCC or Lynch Syndrome). While HNPCC poses the greatest risk of colorectal cancer, women with HNPCC have about a 12 percent lifetime risk of developing ovarian and a 40-60 percent chance of developing uterine cancer.
Women with a grandmother, mother, daughter or sister with ovarian cancer but no known genetic mutation still have an increased risk of developing ovarian cancer. The lifetime risk of a woman who has a first degree relative with ovarian cancer is five percent (the average woman’s lifetime risk is 1.4 percent).
While it accounts for only a limited number of cases, heredity is a strong risk factor for ovarian cancer. Family history should be considered; however, many women without a family history may still have a gene mutation associated with risk for ovarian cancer. All women diagnosed with ovarian cancer, primary peritoneal or fallopian tube cancer should be referred for genetic counseling and consideration of genetic testing.
Family history of any of the following cancers may indicate an increased risk: Breast cancer, Ovarian cancer, Colon cancer, Uterine cancer, Rectal cancer.
Personal history of cancer or endometriosis
Women who have had cancer of the breast, uterus, colon or rectum have a higher risk of ovarian cancer. Having endometriosis increases the risk of clear cell and endometrioid ovarian cancers 2-3 fold.
All women are at risk of developing ovarian cancer regardless of age; however ovarian cancer rates are highest in women aged 55-64 years. The median age at which women are diagnosed is 63, meaning that half of women are younger than 63 when diagnosed with ovarian cancer and half are older.
Reproductive History and Infertility
Research suggests a relationship between the number of menstrual cycles in a woman’s lifetime and her risk of developing ovarian cancer. A woman is at an increased risk if she:
started menstruating at an early age (before 12)
has not given birth to any children,
had her first child after 30,
experienced menopause after 50,
has never taken oral contraceptives.
Infertility, regardless of whether or not a woman uses fertility drugs, also increases the risk of ovarian cancer.
Hormone Replacement Therapy
Doctors may prescribe hormone replacement therapy to alleviate symptoms associated with menopause (hot flashes, night sweats, sleeplessness, vaginal dryness) that occur as the body adjusts to decreased levels of estrogen. Hormone replacement therapy usually involves treatment with either estrogen alone (for women who have had a hysterectomy) or a combination of estrogen with progesterone or progestin (for women who have not had a hysterectomy).
Women who use menopausal hormone therapy are at an increased risk for ovarian cancer. Recent studies indicate that using a combination of estrogen and progestin for five or more years significantly increases the risk of ovarian cancer in women who have not had a hysterectomy. Ten or more years of estrogen use increases the risk of ovarian cancer in women who have had a hysterectomy.
Various studies have found a link between obesity and ovarian cancer. A 2009 study found that obesity was associated with an almost 80 percent higher risk of ovarian cancer in women 50 to 71 who had not taken hormones after menopause.
Factors that may Reduce the Risk of Ovarian Cancer:
Women can reduce the risk of developing ovarian cancer in many ways; however, there is no prevention method for the disease. All women are at risk because ovarian cancer does not strike only one ethnic or age group. A health care professional can help a woman identify ways to reduce her risk as well as decide if consultation with a genetic counselor is appropriate.
Oral Contraceptive Use
The use of oral contraceptives (birth control pills) decreases the risk of developing ovarian cancer, especially when used for several years. Women who use oral contraceptives for five or more years have about a 50 percent lower risk of developing ovarian cancer than women who have never used oral contraceptives.
Pregnancy and Breastfeeding
Pregnancy and breastfeeding are linked with a reduced risk of ovarian cancer, likely because women ovulate less frequently when pregnant or breastfeeding. Multiple pregnancies or having first full-term pregnancy before the age of 26 decreases risk.
Removal of the Ovaries and Fallopian Tubes
Women can greatly reduce their risk of ovarian cancer by removing their ovaries and fallopian tubes, a procedure known as prophylactic bilateral salpingo oophorectomy. Primary peritoneal cancer, which is microscopically almost identical to ovarian cancer, can still occur, but is infrequent. One recent study suggests that women with BRCA1 mutations gain the most benefit by removing their ovaries before age 35.
There are risks associated with removing the ovaries and fallopian tubes; women should speak to their doctors about whether this procedure is appropriate for them.
Having a hysterectomy, or removal of the uterus while leaving the ovaries, may decrease the risk of ovarian cancer by 33 percent, according to the American Cancer Society. Having fallopian tubes tied (tubal ligation) may reduce risk by up to 67 percent, the American Cancer Society says, though researchers aren’t sure why this is the case.
Symptoms of Ovarian Cancer
Ovarian cancer does have symptoms, but they are often very subtle and easily mistaken for other, more common problems. In some rare cases, early stage ovarian cancers may produce symptoms, but in the majority of women these don’t show up until the cancer has advanced (when the growth of the tumor triggers symptoms). Several studies show that ovarian cancer can produce these symptoms:
Pelvic or abdominal pain
Difficulty eating or feeling full quickly
Urinary symptoms (urgency or frequency)
Women with ovarian cancer report that symptoms are persistent and represent a change from normal for their bodies. The frequency and/or number of such symptoms are key factors in the diagnosis of ovarian cancer. See your doctor, preferably a gynecologist, if you have these symptoms for more than two weeks, and the symptoms are new or unusual for you.
While knowing the symptoms is important, inasmuch as it may hasten a diagnosis, research has shown that symptom recognition alone is not useful in detecting ovarian cancer early and that earlier symptom recognition may not alter the course of the disease or outcome. More research is needed to find better ways to identify ovarian cancer, and to treat it more successfully.
Other Symptoms Associated with Ovarian Cancer
Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these other symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women in the general population who do not have ovarian cancer.
Early Detection of Ovarian Cancer
No reliable screening or early detection tests exist for ovarian cancer. The Pap test does not test for ovarian cancer; it screens for cervical cancer.
If a woman has the signs and symptoms of ovarian cancer, her doctor will probably perform a complete pelvic exam, a transvaginal or pelvic ultrasound, radiological tests, such as a transvaginal ultrasound or CT scan, and a CA-125 blood test. Used individually, these tests are not definitive; they are most effective when used in combination with each other. If a woman has a strong family history or a genetic predisposition such as a BRCA mutation, doctors may use some of these tests to monitor a woman.
Among the blood tests your doctor could order is the CA-125 blood test. CA-125 is a substance in the blood that may increase when a cancerous tumor is present; this protein is produced by ovarian cancer cells and is elevated in more than 80 percent of women with advanced ovarian cancers and in 50 percent of those with early-stage cancers. CA-125, however, is approved by the Food and Drug Administration to monitor the effectiveness of treatment for ovarian cancer and for detecting disease recurrence after treatment. The protein CA-125 exists in greater concentration in cancerous cells.
Although the CA-125 blood test is more accurate in postmenopausal women, it is not a reliable early detection test for ovarian cancer. In about 20 percent of advanced stage ovarian cancer cases and 50 percent of early stage cases, the CA-125 is not elevated even though ovarian cancer is present. As a result, doctors generally use the CA-125 blood test in combination with a transvaginal ultrasound. Because CA-125 misses half of early cancers and can be elevated by benign conditions, the National Cancer Institute does not endorse using it to screen women for ovarian cancer who are at ordinary risk or in the general population.
OVA1 has also been approved by the Food and Drug Administration (FDA) for risk stratification. A woman who presents with a known tumor may have this test to determine if her surgery should be done by a gynecologist or a gynecologic oncologist – doctors who are specially trained to treat women with gynecologic cancers. The test measures the levels of five proteins in blood that change when ovarian cancer is present. However, this test has not been approved for use as an ovarian cancer screening tool, nor has it been proven to result in early detection or reduce the risk of death from this disease.
Inhibin B and Inhibin A
Granulosa cell tumors are most often detected and/or monitored via the following blood indicators: Inhibin B and Inhibin A.
A transvaginal ultrasound is a test used to examine a woman’s reproductive organs and bladder, and can often reveal if there are masses or irregularities on the surface of the ovaries and within cysts that form within the ovaries. To administer the test, the doctor inserts a probe into the woman’s vagina. The probe sends off sound waves which reflect off body structures. The waves are then received by a computer that turns them into a picture. An ultrasound alone is not an accurate way to screen for ovarian cancer.
A pelvic exam may be included as part of a woman’s regular female health exam. This exam requires the doctor to place one or two fingers into a woman’s vagina and another over her abdomen to feel the size, shape, and position of the ovaries and uterus. Ovarian cancer is rarely detected in a pelvic exam and usually in an advanced stage if it is.
Recto-vaginal Pelvic Examination (also called a bimanual exam)
This exam allows your doctor to examine the ovaries for lumps or changes in shape or size. Every woman should undergo a rectal and vaginal pelvic examination at her annual check-up with her gynecologist. A Pap test is routine in a pelvic exam but it detects cervical cancer, not ovarian cancer.
The only definitive way to determine if a patient has ovarian cancer is through surgery and biopsy. Doctors will perform surgery after they obtain enough evidence from their exam and test results. If there is a suspicion from these tests that ovarian cancer might be present, the patient should seek a referral to a gynecologic oncologist before surgery occurs. Research shows that women treated by gynecologic oncologists live longer than those treated by other physicians.
Navigating and understanding treatment options are critical for an ovarian cancer patient’s survival. All treatment decisions should be made by a patient in consultation with her medical professional.
The standard treatment for ovarian cancer consists of debulking surgery followed by six rounds of chemotherapy. One recent study found that just 37 percent of women receive this standard treatment, despite evidence showing that it is the most effective.
The goal of treatment for ovarian cancer is to surgically remove as much of the cancer as possible through the debulking and then to provide what is called adjuvant, or additional therapy, such as chemotherapy, to kill any possibly remaining cancer cells in the body. Radiation therapy, which uses high energy rays to kill cancer cells, is not typically utilized in ovarian cancer.
After an Ovarian Cancer Diagnosis
Before surgery, a doctor, preferably a gynecologic oncologist, will explain to a woman the nature of the operation and the extent of tissue that will be removed. During the operation, the doctor will assess how far the tumor has spread, to determine the stage of the cancer, and will give tissue samples to a pathologist, who will determine the grade of the cancer.
After the operation, the doctor will discuss the nature of the chemotherapy that will be given, which will depend on the stage of the disease and how much of the tumor was removed. A doctor might also offer a woman the possibility of enrolling in a clinical trial, if she meets the criteria for the research study. See Clinical Trials section.
Making a list of questions before an appointment with a doctor can be useful because the shock and stress of the diagnosis can make it hard to remember things and medical care can be complicated and difficult to understand. Taking notes of the doctor’s responses or having a friend or relative with you during appointments can be helpful.
Here are some questions the National Cancer Institute suggests you might consider asking a doctor early in treatment:
What is the stage of my disease? Has the cancer spread from the ovaries? If so, to where?
What are my treatment choices? Do you recommend intraperitoneal chemotherapy for me? Why or why not?
Would a clinical trial be appropriate for me?
Will I need more than one kind of treatment?
What are the expected benefits of each kind of treatment?
What are the risks and possible side effects of each treatment? What can we do to control side effects? Will they go away after treatment ends?
What can I do to prepare for treatment?
How long will I need to stay in the hospital? Can I get chemotherapy at my local hospital since it is too far to drive to a major medical center?
What is the treatment likely to cost? Will my insurance cover the cost?
How will treatment affect my normal activities?
Will treatment cause me to go through early menopause?
Will I be able to get pregnant and have children after treatment?
How often should I have checkups after treatment?
If a woman doesn’t feel comfortable with a doctor or wants to seek a second opinion about her care, she has the right to do so.
During surgery, doctors attempt to remove all visible tumors (tumor debulking). Women whose surgery was performed by a gynecologic oncologist have better outcomes than patients whose surgeons were not oncologists, including improved survival and longer disease-free intervals.
Patients undergo chemotherapy in an effort to kill any cancer cells that remain in the body after surgery. Women will usually have either systemic chemotherapy or systemic chemotherapy and intraperitoneal therapy. Besides the gynecologic oncologist (or medical oncologist for those women in rural areas who don’t have access to a gynecologic oncologist) taking care of you, a chemotherapy nurse will assist in providing the drug treatment that will attempt to kill remaining cancer cells in the body. The chemotherapy nurse is a very important health care professional in a patient’s life because s/he assesses the side effects of the drugs and helps alleviate them. Side effects are common with chemotherapy and depend on the type and length of treatment. Each woman is different in her response to chemotherapy and the doctor and nurse will explain possible side effects and provide suggestions and treatments about ways to manage them.
This therapy places the medicine directly into the peritoneal area through a surgically implanted port and catheter. While intraperitoneal (IP) therapy has been in use since the 1950s, new advances have combined it with intravenous (IV) therapy, using chemotherapy agents that work best for treating ovarian cancer. The National Cancer Institute recommends that, for select ovarian cancer patients, chemotherapy be given by both IV and IP. This combination has been found to increase survival for women with advanced stage ovarian cancer.
Some patients may receive chemotherapy before having surgery to remove their tumors. This is known as neoadjuvant chemotherapy.
Other drugs, including angiogenesis inhibitors and targeted therapies, may be recommended either in conjunction with chemotherapy or as single agents. These drugs may have very different side-effects than chemotherapies and may be useful only for specific populations.
Radiation Therapy or Radiotherapeutic Procedures
These procedures may be used to kill cancer cells that remain in the pelvic area.
Researchers carry out ovarian cancer clinical trials to find ways of improving medical care and treatment for women with this disease. A woman is eligible to participate in a clinical trial at any point in her experience with ovarian cancer: before, during or after treatment. Many women think of clinical trials as an option only after other treatments have failed. In reality, many equally important trials are available for women earlier in their fight against ovarian cancer. Learn about the clinical trial process.
With a diagnosis of cancer, some women might opt to try complementary to help themselves. Complementary therapies are those used along with conventional medicine. Acupuncture, massage therapy, herbal products, vitamins, special diets and meditation are examples of these approaches. You should talk with your doctor about treatments you may use because although products, such as herbal teas, are routinely sold, they may interact with cancer drugs and change the drugs’ effectiveness. More and more healthcare facilities these days are offering integrated medical approaches that combine both conventional and complementary therapies for which there is evidence of safety and effectiveness.
Gynecologic Oncologists and Treatment
A gynecologic oncologist is a specialist in treating women’s reproductive cancers. Women with ovarian cancer are strongly encouraged to seek care from one of these specialists.
Multiple studies conducted over the past decade have shown that an ovarian cancer patient’s chance of survival is significantly improved when her surgery is performed by a gynecologic oncologist. One analysis of multiple studies found that women whose surgeries were performed by gynecologic oncologists had a median survival time that was 50 percent greater than women whose surgeries were done by general gynecologists or other surgeons inexperienced in optimal debulking procedures.
Sometimes referred to as cytoreductive surgery, debulking involves removal of as much of the tumor as possible. As part of the debulking procedure, doctors try to stage the disease definitively and identify the optimal treatment for the cancer. Proper staging and optimal debulking translate into improved overall survival for women at any stage of ovarian cancer.
Gynecologic oncologists have greater success in treating ovarian cancer as a result of their tendency to perform more aggressive surgery. Women whose tumors have been reduced to less than one centimeter have a better response to chemotherapy and improved survival rate. Gynecologic oncologists also are more likely to perform the multiple peritoneal and lymph node biopsies necessary to ensure adequate surgical staging.
To locate a gynecologic oncologist in Indiana, download our RESOURCES AND SUPPORT document or visit the Foundation for Women’s Cancer website.
When cancer returns after a period of remission, it is considered a recurrence.
A cancer recurrence happens because some cancer cells were left behind and eventually grow and become apparent. The cancer may come back to the same place as the original tumor or to another place in the body. Around 70 percent of patients diagnosed with ovarian cancer will have a recurrence.
One of the factors in determining a patient’s risk of recurrence is the stage of the cancer at diagnosis:
Patients diagnosed in stage I have a 10 percent chance of recurrence.
Patients diagnosed in stage II have a 30 percent chance of recurrence.
Patients diagnosed in stage III have a 70 to 90 percent chance of recurrence.
Patients diagnosed in stage IV have a 90 to 95 percent chance of recurrence.
Recurrent ovarian cancer is treatable but rarely curable. Women with recurrent ovarian cancer may have to undergo another surgery. Because many women with recurrent ovarian cancer receive chemotherapy for a prolonged period of time, sometimes continuously, the toxicities of therapy are a major factor in treatment decisions.
Treatment for Ovarian Cancer Recurrence
The effectiveness and type of treatment for recurrent ovarian cancer depends on what kind of chemotherapy the patient received in the past, the side effects associated with previous treatments, the extent of the recurrent cancer and the length of time since the last treatment was finished called the “time to recurrence,” which researchers often call “progression-free survival.”
The “time to recurrence” is the amount of time between your response to a prior platinum-based chemotherapy and the time of the recurrence.
If the time to recurrence is less than six months, the ovarian cancer is classified as platinum-resistant, and the woman will be treated with usually one other type of chemotherapy drug. Women are encouraged to consider participating in a clinical trial that might offer an opportunity to take a new investigational drug that could be helpful.
If the time to recurrence is more than six months, the ovarian cancer is classified as platinum-sensitive and the woman will be treated with a platinum-based drug again and another chemotherapy agent.
During treatment for recurrence, it is very important to have a continual dialogue with your doctor about the benefits of treatment, with respect to remission and survival, versus the risks of the side effects that hurt the quality of your life. If you do choose treatment in recurrence, there are several options based on your previous treatments.
Chemotherapy is used to stop the progression of cancer and prolong the patient’s survival. Sometimes, surgery is used to relieve symptoms, such as a blocked bowel caused by the recurrence. In select patients, surgery for debulking of cancer is also an option. It is important to stress again that you, in consultation with your doctor, should set realistic goals for what to expect from treatment. This may mean weighing the possible positive outcomes of a new treatment against the possible negative ones. At some point, a woman may decide that continuing treatment is unlikely to improve her health or survival. A woman must be certain that she is comfortable with her decision whatever it is.