Highlights
Ovarian Cancer Symptoms
Even early-stage ovarian cancer can produce symptoms, according to a 2007 consensus statement issued by the American Cancer Society, the Gynecologic Cancer Foundation, and the Society of Gynecologic Oncologists. Because ovarian cancer can grow very rapidly, early detection is extremely important. Contact your doctor (preferably a gynecologist) if you experience these symptoms on a daily basis for more than a few weeks:
- Bloating
- Pelvic or abdominal pain
- Difficulty eating or feeling full quickly
- Urgent or frequent urination
Hormone Replacement Therapy (HRT) Increases Ovarian Cancer Risk
- Post-menopausal women who use hormone replacement therapy (HRT) for more than 5 years are 20% more likely to develop ovarian cancer than women who do not use HRT, suggests a 2007 study in the Lancet. Researchers analyzed data from more than 1 million women.
- A similar association between HRT use and ovarian cancer, especially for women who have not had a hysterectomy, was reported in a 2006 study in the Journal of the National Cancer Institute.
Surgery
- About 1 in 3 women with ovarian cancer fail to receive recommended surgical treatment, according to a 2007 study in Cancer. The study found that women who are poor, African-American or Hispanic, or over age 70 are least likely to receive adequate care. Another Cancer study suggested that although experienced cancer centers may cost more than other facilities, they are more cost-effective over the long term than less experienced medical facilities.
- For optimal ovarian cancer treatment, it is best to seek care from an experienced gynecologic oncologist and specialized cancer center.
Investigational Drugs
Aflibercept (VEGF-TRAP), an experimental anti-angiogenesis drug, may benefit patients with epithelial ovarian cancer who have not been helped by platinum-based chemotherapy, according to interim results of a Phase II study presented at the 2007 annual meeting of the American Society of Clinical Oncology. Anti-angiogenesis drugs prevent tumors from growing and spreading by starving them of their blood supply.
Introduction
The ovaries are two small, almond-shaped organs located on either side of the uterus. They are key components of a woman's reproductive system:
- Ovaries store 200,000 - 400,000 follicles, tiny sacs that are present from birth, that nurture immature eggs (ova).
- During each normal (usually monthly) reproductive cycle, a follicle in one ovary bursts and releases a mature or "ripened" egg. The egg travels down the fallopian tube into the uterus, where it either is fertilized by a man's sperm or, if unfertilized, breaks down and is excreted as part of the menstrual cycle.
- Ovaries also secrete the important reproductive hormones estrogen and progesterone.
Ovarian cancers are potentially life-threatening malignancies that develop in one or both ovaries. Malignant ovarian tumors generally fall into three primary classes:
- Epithelial tumors
- Germ cell tumors
- Stromal tumors
Epithelial Tumors. Epithelial tumors account for up to 90% of all ovarian cancers and therefore are the primary focus of this report. These cancers develop in a layer of cube-shaped cells known as the germinal epithelium, which surrounds the outside of the ovaries.
Germ Cell Tumors. Germ cell tumors, which account for about 3% of all ovarian cancers, are found in the egg-maturation cells of the ovary. They occur most often in teenagers and young women. Although they progress rapidly, they are very sensitive to treatments. About 90% of patients with germ cell malignancies can be cured, often preserving fertility.
Stromal Tumors. Stromal tumors, which account for 6% of all ovarian cancers, develop from connective tissue cells that hold the ovary together and that produce the female hormones, estrogen and progesterone. Stromal tumors do not usually spread, in which case the prognosis is good. If they spread, however, they can be more difficult to treat than others.
Click the icon to see an image of ovarian cancer.
Ovarian cancer is called the silent killer because it progress almost silently, with vague symptoms. By the time symptoms do appear, the ovarian tumor may have grown large enough to shed cancer cells throughout the abdomen. At such an advanced stage, the cancer is more difficult to cure.
Ovarian cancer cells that have spread outside the ovaries are referred to as metastatic ovarian cancers. Ovarian tumors tend to spread to the following locations:
- Diaphragm
- Intestine
- Omentum (a fatty layer that covers and pads organs in the abdomen)
Cancer cells can also spread to other organs through lymph channels and the bloodstream.
Not all ovarian tumors are malignant. Benign cysts, dermoid tumors, and borderline malignant tumors all are distinct from ovarian cancer.
Benign Cysts. Benign cysts are common. They typically develop in one of two ways:
- Follicular Cysts. During normal ovulation, follicles (the little sacs in the ovary) expel eggs. If the egg is not expelled, fluids and other substances can build up inside the follicle, forming a follicular cyst.
- Corpus Luteum Cysts. Benign cysts may form when an egg has been released, but the emptied follicle (now called the corpus luteum) does not break down normally, instead filling with blood from nearby blood vessels.
Both follicular cysts and corpus luteum cysts are normal parts of the menstrual cycle and nearly always resolve within one or two cycles without treatment.
Dermoid Tumors. Dermoid tumors are benign growths that occur when an egg begins to develop without fertilization by a sperm; they can contain hair, teeth, and cartilage. They are easily removed by surgery.
Borderline Ovarian Tumors. About 15% of ovarian tumors are referred to as "borderline" because their appearance and behavior under the microscope is between benign and malignant. These tumors are often referred to as carcinomas of low malignant potential because they rarely metastasize or cause death. Even when borderline carcinomas do spread outside the ovary, only 10 - 20% are fatal.
Symptoms
Ovarian cancer used to be considered a “silent killer." Symptoms were thought to appear only when the cancer was in an advanced stage. Now, experts know this is not true -- even early-stage ovarian cancer can produce symptoms.
In June 2007, the Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists, and the American Cancer Society released a consensus statement concerning ovarian cancer symptoms. If you have the following symptoms on a daily basis for more than a few weeks, you should see your doctor (preferably a gynecologist):
- Bloating
- Pelvic or abdominal pain
- Difficulty eating or feeling full quickly
Ovarian cancer grows quickly and can progress from early to advanced stages within a year. Paying attention to symptoms can help improve a woman's chances of being diagnosed and treated promptly. Detecting cancer while it is still in its earliest stages can help improve prognosis. Even a few months delay in detection may affect survival.
Other symptoms are also sometimes associated with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain during intercourse, constipation, and menstrual irregularities. However, according to experts, these symptoms are not as useful in diagnosing ovarian cancer, because they are also commonly experienced by women who do not have cancer.
Based on the symptoms and physical examination, the doctor may order pelvic imaging tests or a CA-125 blood test. If these tests reveal signs of cancer, patients should be referred to a gynecologic oncologist or a surgeon who specializes in female reproductive system cancers.
Causes
About 22,430 new cases of ovarian cancer are expected in the United States in 2007. Evidence suggests that the incidence of ovarian cancer is declining. The average age for the onset of ovarian cancer is about 60, although ovarian cancer can develop in women from the ages of 20 - 90. The lifetime risk of ovarian cancer in women with no family history of the disease is approximately one in 70 (1.4%).
Women with a history of ovarian cancer in one first-degree relative (mother or sister) have an overall 5% risk of developing the disease, but it may be higher in women with specific genetic factors. The majority of women with ovarian cancer have no family history of the disease, however, meaning that genetic inheritance is not the only risk factor.
Genetic mutations causing abnormal cell growth and differentiation are the basis for all cancer. The great majority of genetic defects that cause cancer are due to unknown causes. Most likely overexposure to environmental assaults, or errors that occur during cell division, play a role in many cases.
Several circumstances that create hormonal changes may increase the risk of ovarian cancer.
Number of Ovulations. Risk of ovarian cancer is directly related to the number of times a woman ovulates, which is indicated by the total number of menstrual periods she has had. A lower number of ovulations occur when the menstrual periods are shut off (as in pregnancy), so the risk of developing ovarian cancer is reduced.
The following women have a lower risk for ovarian cancer:
- Women with a history of multiple pregnancies.
- Women who took birth control pills (these shut off the menstrual period).
- Women who breast-fed. (The body usually does not release eggs while a woman is breast-feeding.)
Some researchers theorize that ovarian cancer develops in women with a higher number of ovulations because of persistent damage to the epithelial cells as the egg passes through during ovulation. Researchers postulate that the recurring cell division needed to heal these tiny wounds to the ovaries, month after month and year after year, creates opportunities for errors in cell reproduction that lead to the formation of cancerous cells. Therefore, the more ovulations, the more risk of ovarian cancer. Ovulation temporarily ceases during pregnancy, breast-feeding, and birth control pill use.
Gonadotropins and Fertility Drugs. Gonadotropins are hormones produced in the pituitary gland that stimulate the ovaries to secrete estrogen and cause the follicles to produce and release eggs.
In a few studies, elevated levels of gonadotropins have been associated with an increased risk for ovarian cancer. These hormones are the basis for many fertility drugs, including human menopausal gonadotropin (Pergonal, Repronal, Metrodin) and clomiphene (Clomid, Serophene). Although there has been concern about an increased risk for ovarian cancers in women, a growing body of evidence is finding no higher risk from the drugs themselves. Instead, evidence suggests that ovarian cancers are most likely caused by factors contributing to the infertility -- not the drugs used to treat it.
Hormone Replacement Therapy. Hormone replacement therapy (HRT) appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT. Another important study, from the U.S. National Cancer Institute, indicated that 5 or more years of combination HRT (estrogen and progestin) increases the risk of ovarian cancer for women who have not had a hysterectomy.
Family history plays a role in 5 - 10% of women who have ovarian cancer. Certain genes are being investigated and identified that are responsible for some of these cases. Depending on the particular genetic type, the lifetime risk for ovarian cancer in women who carry these genes ranges from 16 - 65%.
BRCA1 and 2 Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30 - 50% of breast cancers, ovarian cancers, or both in patients with a strong family history of these cancers.
According to some studies, the risks are as follows:
- Studies indicate that about 25 - 40% of women who carry the abnormal BRCA1 gene may develop ovarian cancer.
- The risk for women with the BRCA2 gene mutation is generally believed to be lower, about 9 - 15%.
The mutated genes are linked to an even higher risk for developing breast cancer. These mutations are present in only about 0.5% of the U.S. population overall but occur in about 2.5% of all Jewish women of Eastern European (Ashkenazi) descent. These mutations are not restricted to the Ashkenazi population and may occur in women of any ethnicity, including women of Asian and African descent.
Either a mother or father can pass down BRCA mutations to the daughter. These mutations may also occur in 5 - 10% of ovarian cancer patients who have no family history of breast or ovarian cancer. A number of studies have suggested that women with BRCA-mutated ovarian cancers tend to have better survival rates than other women.
A 2005 study in the Journal of the National Cancer Institute indicated that women who have a family history of breast cancer, but no history of BRCA genetic mutations, are not at increased risk for ovarian cancer.
Other Genetic Mutations. Women who carry the hereditary nonpolyposis colorectal cancer (HNPCC) gene have about a 9% chance of developing ovarian cancer.
Risk Factors for Inherited Ovarian Cancer. Women are considered at high risk for ovarian cancer if they have:
- A first-degree relative (mother, sister, or daughter) with ovarian cancer at any age. The risk increases with the number of affected first-degree relatives.
- A first-degree relative (or two second-degree relatives on the same side) with early onset breast cancer (occurring before age 50).
- A family member with both breast and ovarian cancer.
- A family history of male breast cancer (which might indicate a BRCA2 mutation).
- A family history of hereditary nonpolyposis colorectal cancer.
When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant.
Screening High-Risk Women. It is now possible to test for genetic mutations in the BRCA1 and BRCA2 genes and for hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers syndrome in high-risk women. Any positive result raises difficult issues:
- The presence of a mutation in any of these genes does not predict with absolute certainty that either breast cancer or ovarian cancer will occur. The lifetime risk for BRCA1, for example, is significantly higher (up to 40%) than for BRCA2 (about 10 - 15%).
- Surgical preventive strategies, which can involve both mastectomy and removal of the ovaries, do not completely eliminate the risk for cancer, since malignant cells may occur in nearby regions. Removal of the ovaries will reduce ovarian cancer risk, however, and may also reduce breast cancer risk in mutation carriers.
Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA1 or BRCA2 genetic mutations).
Most ovarian cancers are the result of genetic mutations that are not inherited but occur from environmental or other factors that cause damage to genetic material over time. Such genetic changes are referred to as sporadic (as opposed to inherited). Genetic alterations that have been observed in ovarian cancers involve the p53 tumor suppressor gene, the HER2/neu gene, and the PIC3KA gene.
Some research indicates that ovarian cancer occurs more often in North America and Northern Europe and among middle-to-upper socioeconomic class women from highly industrialized countries. Ovarian cancer is also much more common in Caucasian women than in African-American women. Japan has a low, but rising, number of ovarian cancer cases. One study observed that when Japanese women immigrate to the United States, they and their daughters have an incidence of ovarian cancer that approaches that of Caucasian women, although another study did not support such findings.
Pregnancy. Women who have never had children are more likely to develop ovarian cancer than women who have had children. The more children a woman has had, the lower her risk for ovarian cancer.
Obesity. Obesity may increase the risk of developing more aggressive types of ovarian tumors. A 2006 study indicated that a higher body mass index was associated with poorer survival.
Endometriosis. Women with endometriosis may have some higher risk for ovarian cancer. However, endometriosis is very common and ovarian cancer is not, so the risk is still very low. Some research suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases and, in fact, have a better outlook.
Click the icon to see an image of endometriosis.
Fat Intake. Fats have been under scrutiny for some time for putting some women at higher risk for ovarian cancer. A review study reported an association between a high intake in animal fats and a greater risk. However, other studies on this subject have found no correlation between fat intake and ovarian cancer.
Prevention
No specific lifestyle factors are proven to protect against ovarian cancer, although the following study results suggest some lower or higher risk:
- Some studies have suggested a lower rate of ovarian cancer in women who eat a diet rich in vegetables. The American Cancer Society recommends that women eat 5 servings of fruits and vegetables a day, and limit consumption of high-fat red meat.
- A 2005 study of more than 61,000 women suggested that tea consumption may reduce the risk of ovarian cancer. Women in the study who drank at least 2 cups of tea a day (mainly black tea) had a lower risk of ovarian cancer than women who did not drink tea.
- Exercise, which protects against many diseases and even some cancers, appears to have no effect on ovarian cancer. However, obesity is associated with poorer ovarian cancer survival. Women who are obese also have a higher risk for breast cancer. Regular exercise is a good idea in any case.
- Smokers should quit. Although evidence of an association with ovarian cancer is weak, it is always wise to stop smoking.
In general, factors or behaviors that limit stimulation of the ovaries or inhibit ovulation appear to be protective.
Pregnancy. The more times a woman has been pregnant the less likely she is to develop ovarian cancer. One study indicated that ovarian cancer was reduced by 40% with one pregnancy and by an additional 14% with each subsequent pregnancy.
Breast-feeding. Breast-feeding, even for only 1 - 2 months, may also reduce the risk for ovarian cancer by as much as 40%. A longer duration of breast-feeding does not appear to increase its protective benefits.
Oral Contraceptives and Progestin. Studies have suggested that routine use of birth control pills that contain the female hormones estrogen and progestin, even low-dose forms, reduces a woman's risk of ovarian cancer by about 50% when compared to women who have never taken oral contraceptives. The longer a woman takes oral contraceptives the greater the protection and the longer protection lasts after stopping oral contraceptives.
Click the icon to see an illustrated series detailing the birth control pill.
Pregnant women or women with breast cancer should not take birth control pills. Other conditions that may preclude taking oral contraceptives include:
- Liver disease
- Migraines
- Coronary artery disease and any risk factors for heart disease or stroke (particularly smoking, obesity, high blood pressure, blood clotting disorders, or diabetes)
Tubal Ligation. Tubal ligation, a method of sterilization that ties off the fallopian tubes, has been associated with a decreased risk for ovarian cancer in some -- but not all -- studies.
Click the icon to see an image of tubal ligation.
Surgical removal of the ovaries, called oophorectomy, significantly reduces the risk for ovarian cancer. When it is used to specifically prevent ovarian cancer in high-risk women, the procedure is called a prophylactic oophorectomy. Prophylactic oophorectomy is approximately 95% protective against ovarian cancer. It is sometimes recommended for women at high risk for ovarian cancer. These women generally have the BRCA1 or BRCA2 genetic mutation, or have two or more first-degree relatives who have had ovarian cancer.
Bilateral oophorectomy is the removal of both ovaries. Bilateral salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. Several recent studies indicate that salpingo-oophorectomy is very effective in reducing risk for ovarian cancer in women who carry the BRCA1 or BRCA2 mutation.
A 2006 Journal of the American Medical Association study reported that bilateral salpingo-oophorectomy reduces ovarian cancer risk by 80% for women with certain mutations in the BRCA1 and BRCA2 genes. A study presented at the 2006 meeting of the American Society of Clinical Oncology (ASCO) indicated that this procedure is most effective for reducing ovarian cancer risk in women with the BRCA1 gene mutation. For women with BRCA2 gene mutation, the procedure was better at reducing the risk for breast cancer.
Even after oophorectomy, women in high-risk groups for ovarian cancer still have a risk for the development of cancer in the peritoneum (the sac inside the abdomen that holds the intestines, uterus, and ovaries).
Premenopausal women should realize that oophorectomy causes immediate menopause, which poses a risk for several health problems, including osteoporosis, heart disease, and reduction in muscle tone. Estrogen replacement can help offset these problems. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.
Diagnosis
Up to 95% of women diagnosed with ovarian cancer will survive longer than 5 years if their cancers are treated before they have spread beyond the ovaries. Unfortunately, there are no screening tests for ovarian cancer that are the equivalent to mammography for early detection of breast cancer. Therefore, only about 25% of ovarian cancer cases are diagnosed at such early stages. It is possible to perform genetic screening in high-risk women, but this raises some complex issues.
Every woman should have a regular annual examination with her doctor that includes:
Pelvic examination. Routine exams called bimanual pelvic examinations are a reasonable precaution, although they are not perfect screening methods due to their low sensitivity. This exam can be performed two ways. In the more common method, the doctor inserts two fingers into the vagina while palpating the abdomen with the other hand. The other method, called a bimanual rectovaginal exam, involves the insertion of one finger into the vagina and another into the rectum.
Either exam enables the doctor to assess the size of the ovaries as well as the contour and mobility of the uterus and to feel for masses and growths. The rectovaginal exam may reveal rectal lesions that may otherwise go unnoticed and is particularly important for women over 50. A mass felt on pelvic exam often requires further evaluation by ultrasound and sometimes requires surgery to make a definitive diagnosis.
Pap smear. This test is specifically designed to detect cervical cancer. In very rare instances, however, it may reveal abnormal ovarian cells, which might indicate the presence of an ovarian cancer.
Click the icon to see an image of a pap smear.
Unfortunately, ovarian cancer rarely produces changes that are detectable during a regular checkup.
An estimated 290,000 women are hospitalized each year in the United States because of ovarian growths or lesions. Many more women find out about some ovarian abnormality during their annual Ob/Gyn check up. The vast majority of conditions are noncancerous. They include:
- Benign functional ovarian cysts
- Abscesses and infection
- Fibroids
Click the icon to see an image of a fibroid tumor.
- Endometriosis
- Polycystic ovaries
Click the icon to see an image of a polycystic ovary.
- Ectopic pregnancies
Click the icon to see an image of an ectopic pregnancy.
- Meig syndrome (which involves a benign ovarian growth associated with fluid buildup in the abdomen and around the lungs)
- Ovarian hyperstimulation syndrome following fertility treatments.
Once a growth is detected, additional tests [below] may help the doctor gauge the risk for it being cancerous.
Ultrasound. Ultrasound is a noninvasive diagnostic tool that can evaluate tumors and masses discovered during the rectovaginal exam:
- Typically, a probe is placed in the vagina and emits sound waves (ultrasound). The sound waves bounce off tissues, organs, and masses in the pelvic cavity. These echoes are collected and converted into a picture of the area called a sonogram.
Click the icon to see an image of transvaginal ultrasound.
- The ultrasound probe may also be placed on abdominal walls above the ovaries (transabdominal ultrasound), but it does not provide as clear a picture of the ovaries. Healthy tissue, fluid-filled cysts, and solid tumors produce different sound waves.
Ultrasound is not helpful for identifying early-stage ovarian cancer in high-risk women. (Researchers hope that blood tests for protein markers may eventually provide a better method for diagnosing early-stage ovarian cancer.) In addition, ultrasound does not provide enough specific information to reliably determine which abnormal masses are cancerous or noncancerous.
- Studies suggest that small so-called simple cysts (fluid-filled without an associated mass) are usually noncancerous, particularly when they appear in premenopausal women whose blood tests for the protein CA-125 are normal. Such women are sometimes given oral contraceptives and observed for a few months to see if the cyst goes away.
- Postmenopausal women with small simple cysts and normal CA-125 levels may sometimes be observed for a time if they have no other risk factors or symptoms of ovarian cancer.
- In contrast, a "complex" cyst (one that shows a mass or other abnormalities) is often surgically removed, since it has a higher chance of being malignant. Only a small percentage of these cysts turn out to be cancerous. (In one study 6% of complex cysts were actually cancerous.)
Click the icon to see an image of an ovarian cyst.
Other Imaging Techniques. Other imaging techniques are less common for the diagnosis or evaluation of suspected ovarian cancer but may help determine if cancer has spread to other parts of the body:
- Computed tomography (CT). Computed tomography records x-ray absorption rates of tissue and bone. These data is converted into clear images on a screen. CT scans help determine if cancer has spread to the lymph nodes, abdominal organs, abdominal fluid, and the liver.
Click the icon to see an image of a CT scan.
- Magnetic resonance imaging (MRI). MRI creates multiple cross-sectional images of the pelvis and abdominal organs, which are assembled into three-dimensional images. An MRI is not usually used to diagnose ovarian cancer, but may help determine if cancer has spread to the brain or spinal cord.
Click the icon to see an image of a MRI scan.
- Chest x-rays. Find cancer that has spread to the lungs.
Click the icon to see an image of an x-ray machine.
CA-125 is a protein that is secreted by ovarian cancer cells and is elevated in over 80% of patients with ovarian cancer. The CA-125 blood test is not approved for screening in the general population. Oncologists will usually only obtain a blood test for this protein if ovarian cancer is strongly suspected or has been diagnosed. In general, a CA-125 level is considered to be normal if it is less than 35 U/mL (microns per milliliter). The test may also be useful for evaluating tumor growth and predicting survival in patients with recurrent cancer who have been treated with topotecan or paclitaxel-carboplatin chemotherapy regimens.
The test is not useful for diagnosis or early screening, however. In about half of women with very early ovarian cancer, CA-125 levels are not elevated above the normal standard at all. Furthermore, an elevated level can be caused by a number of other conditions including:
- Endometriosis (which may be a risk factor for ovarian cancer)
- Fibroids
- Noncancerous ovarian cysts
- Pregnancy
- Pelvic inflammatory disease
- Liver diseases
- Other tumors, such as breast, colon, lung, and pancreatic cancers
- Age and menstrual status can also affect the levels of CA-125
Research is under way to find better tests that will detect this cancer in early stages.
Proteomics. A promising new approach relies on a technique called proteomics. Proteomics is the analysis of certain proteins. In this approach, researchers are looking at a unique pattern of proteins produced by ovarian cancer cells. Studies suggest this set of proteins serves as an early biomarker for detecting ovarian cancer. Scientists at the National Cancer Institute (NCI) and Food and Drug Administration (FDA) have developed a blood test to check for the presence of these abnormal proteins. In one study, the proteomics tool identified 100% of patients with ovarian cancer and incorrectly diagnosed cancer in only 3 out of 66 of women who were actually cancer-free. A clinical trial is now under way comparing the proteomics test to the CA-125 test. OvaCheck, another investigational ovarian cancer blood test, is based on principles similar to the NCI and FDA platform, but is being developed independently by a private corporation.
Osteopontin. Scientists are also looking into the possibility that the protein osteopontin may be a biomarker for ovarian cancer. Studies have shown that osteopontin is overexpressed in tumors and serum of women with ovarian cancer.
Other Biomarkers. Researchers have also had preliminary success with a blood test that measures osteopontin along with three additional protein markers in blood: leptin, prolactin, and insulin-like growth factor-II. In early trials, prolactin and osteopontin levels were significantly elevated in women with early ovarian cancer. The other two proteins were greatly reduced. When measured collectively, these four proteins completely distinguished between healthy women and those with early ovarian cancer, according to the results published in the May 2005 journal of the Proceedings of the National Academy of Sciences.
An exploratory surgical procedure called laparotomy generally is required for the definitive diagnosis of ovarian cancer. Laparotomy involves the following steps:
- It requires general anesthesia and employs standard surgical techniques to make a vertical, midline incision from the pubic bone to the navel.
- Such an incision ensures careful evaluation of the entire abdominal area. After the incision is made, the surgeon assesses the fluid and cells in the abdominal cavity.
- During this procedure, cysts or other suspicious areas will be removed and biopsied (tested for cancer).
- If the lesion is cancerous, the surgeon continues with a process called surgical staging to find out how far the cancerous tumor has spread and to remove the ovaries and any cancerous tissue.
Investigators are also studying laparoscopy -- instead of more invasive surgery -- for initial surgical evaluation (staging).
Click the icon to see an image of pelvic laparoscopy.
Prognosis
Ovarian cancer ranks behind lung, breast, and colorectal cancer as the fourth most common cause of female cancer death in this country. About 15,280 American women are expected to die from ovarian cancer in 2007.
In general, overall 5-year survival rates (all stages combined) increased from 37% in 1974 to greater than 50% currently. Survival rates vary depending on different factors, including age and the stage at which it is detected.
The survival rate also varies according to the cancer stage:
- Five-year survival rates are over 90% if the cancer is still confined to the ovary at diagnosis. However, only 19% of ovarian cancers are found at this stage.
- If the cancer has spread to nearby regions in the pelvis, the survival rate drops to 60 - 80%.
- If the cancer has spread to sites outside the pelvis, the 5-year survival rates are only 10 - 30%.
Unfortunately, most patients with ovarian cancer are not diagnosed until the disease is advanced. This usually means the cancer has spread to the upper abdomen. In order to establish a prognosis and determine treatment, the doctor needs to know the cell type, stage, and grade of the disease.
About 90% of ovarian epithelial cancers fall into one of four major subtypes based on their origin and shape as viewed under a microscope:
- Serous. (This is the most common type.)
- Endometrioid. (This is sometimes associated with endometriosis and tends to have a more favorable outlook.)
- Mucinous. (The presence of malignant mucinous cells indicates a poorer outlook if the disease is advanced.)
- Clear cell. (Clear cell carcinomas are the most difficult to treat even when the malignancy is still confined to the ovary.)
The remaining 10% of common epithelial cancers are referred to as undifferentiated, because their exact cell of origin cannot be determined microscopically. These epithelial ovarian carcinomas tend to grow and spread quickly.
Cancers are staged (I through IV) according to whether they are still localized (remaining in the ovary) or have spread beyond the original site.
Tumors are also graded according to how well or poorly organized they are (their differentiation). Ovarian tumors are graded on a scale of 1, 2, or 3. Grade 1 tends to closely resemble normal tissue and has a better prognosis than grade 3, which indicates very abnormal, poorly defined tissue.
Age. In general, younger women have a better prognosis than older women although stage and grade of tumor also are important to the prognosis.
BRCA Carriers. Some studies have reported that women who carry mutated BRCA genes may have better survival rates than non-carriers. The survival advantages may be due to having a slower course or being more responsive to therapies than sporadic ovarian cancers, although this is controversial.
Angiogenesis. Experimentally, the level of biochemicals stimulating the formation of new blood vessels that support tumor growth (angiogenesis) appears to correlate with prognosis. The more angiogenic factors present in a tumor population, the more new blood vessels will form, encouraging both tumor growth and metastasis.
Overexpression of p53 Mutations. High levels of a defective p53 gene (which regulates cell growth) are associated with a poorer outlook.
Women who survive ovarian cancer have a high risk for psychological stress. Support groups can be very helpful.
Treatment
In general, the course of treatment is determined by the stage of the cancer. Stages range from I to IV based on the cancer's specific characteristics, such as whether it has spread beyond the ovaries.
In stage I, the cancer has not spread. It is confined to one ovary (stage IA) or both ovaries (stage IB). In stages IA and IB, the ovarian capsules are intact, and there are no tumors on the surface. Stage IC can affect one or both ovaries, but the tumors are on the surface, or the capsule is ruptured, or there is evidence of tumor cells in abdominal fluid (ascites). The overall 5-year survival rate for stage IA or IB can be as high as 90%, but the presence of other factors may affect this rate. For example, non-clear-cell well-differentiated cancer cells or borderline tumors have a favorable prognosis. Clear cells or those that are more poorly differentiated have a worse outlook. Stage IC has a poorer outlook than the earlier stages. It is very important that women receive an accurate staging assessment, including a pathologic review conducted by a gynecologic pathologist.
Treatment Options: Treatment for most women with stage IA and IB includes surgical removal of the uterus and both ovaries and fallopian tubes (total hysterectomy and bilateral salpingo-oophorectomy), partial removal of the omentum (the fatty layer that covers and pads organs in the abdomen), and surgical staging of the lymph nodes and other tissues in the pelvis and abdomen. (Carefully selected premenopausal women in Stage I with the lowest-grade tumors in one ovary may sometimes be treated only with the removal of the diseased ovary and tube in order to preserve fertility.) Patients with stage IA or B disease, grade 1 (or sometimes grade 2), usually do not need further therapy after surgery. However, higher risk patients (stage IC, stage I/grade 3) are usually treated with platinum-based chemotherapy to reduce their risk of subsequent relapse.
A 2005 study suggested that adjuvant platinum-based chemotherapy (chemotherapy added to surgical treatment) can improve survival and reduce cancer recurrence. With the considerable adverse effects of chemotherapy, more research is needed to determine which stage 1 patients would benefit most from this adjuvant treatment.
Click the icon to see an illustrated series detailing hysterectomy.
In stage II, the cancer has spread to other areas in the pelvis. It may have advanced to the uterus or fallopian tubes (stage IIA), or other areas within the pelvis (stage IIB), but is still limited to the pelvic area. Stage IIC indicates capsular involvement, rupture, or positive washings (that is, they contain malignant cells). The 5-year survival rate for stage II is about 60 - 80%.
Treatment Options: Surgical management for most women in this stage is total hysterectomy, bilateral salpingo-oophorectomy, and removal of as much cancer in the pelvic area as possible (tumor debulking). Surgical staging should be performed.
After the operation, treatment with chemotherapy is usually necessary in an attempt to eradicate residual cancer and decrease the chance for relapse.
In stage III, one or both of the following are present: (1) The cancer has spread beyond the pelvis to the omentum (the fatty layer that covers and pads organs in the abdomen) and other areas within the abdomen, such as the surface of the liver or intestine. (2) The cancer has spread to the lymph nodes. The average 5-year survival rate for this stage is 20%.
Click the icon to see an image of the lymph system located near the ovaries.
Treatment Options: Surgical management for most women in this stage is total hysterectomy and bilateral salpingo-oophorectomy and removal of as much cancer as possible (tumor debulking).
Following surgery, chemotherapy is usually needed for any remaining cancer cells. Several approaches are under investigation for reducing high rates of recurrence (about 80%). These approaches include the following:
- Experimental chemotherapy drugs
- Anti-angiogenic therapies
- Gene and biological therapies
- Intraperitoneally administered high-dose chemotherapy
- Neoadjuvant therapy (chemotherapy before surgery)
- High-dose chemotherapy
- Peripheral blood stem cell transplantation (to date this approach has proven to be very toxic with no convincing improvement in survival)
Stage IV is the most advanced cancer stage. The cancer may have spread to the inside of the liver or spleen. There may be distant spreading of the cancer, such as ovarian cancer cells in the fluid around the lungs. The average 5-year survival rate for this stage is less than 10%.
Treatment Options: Tumor debulking may be performed before chemotherapy.
Although not standard practice in the United States, a surgical procedure called retroperitoneal lymphadenectomy is sometimes performed. This procedure involves removal of aortic and pelvic lymph nodes from the rear of the abdomen. Results from a 2005 randomized controlled trial suggest that while retroperitoneal lymphadenectomy does help reduce cancer progression, it does not prolong survival.
Treatment Options: If ovarian cancer returns, chemotherapy is the mainstay of treatment, although it is not generally curative in the setting of relapsed disease.
If the interval between the last platinum-containing chemotherapy (carboplatin or cisplatin) and relapse is long (greater than 6 months), it is reasonable to attempt a repeat trial of platinum-based chemotherapy, with or without paclitaxel.
If the interval is short, or if these drugs fail to control the tumor, other second-line drugs may be useful in achieving a response. They include topotecan, liposomal doxorubicin, etoposide, docetaxel, gemcitabine, or tamoxifen. There is no evidence that second-line drug combinations are any more effective than single drugs, although they are generally more toxic.
Clinical trials using various investigative approaches are under way. It is not clear if there is a role of a second debulking surgical procedure. A 2004 study published in the New England Journal of Medicine found that additional debulking did not prevent cancer progression or prolong survival.
Surgery
Surgery for ovarian cancer uses laparotomy, a major abdominal operation. It is the primary diagnostic tool for ovarian cancer and also plays a role in treatment. Complete surgical intervention includes the following:
- Surgical staging (examining all tissues and organs in the pelvic cavity for accurate assessment of the disease stage).
- Debulking (removal of as much of the cancerous tissue as possible). This is an important component of ovarian cancer management and should be performed by a surgeon trained in cancer surgery techniques.
Patients with ovarian cancer should see a qualified gynecologic oncologist (a surgical specialist in female reproductive cancers) and a qualified medical oncologist with special expertise in the chemotherapeutic management of gynecologic cancer. Studies indicate that it is best for patients, especially those with advanced-stage ovarian cancer, to receive care at medical centers that specialize in cancer treatment and surgery.
According to a 2007 study, 1 in 3 patients with ovarian cancer fails to receive recommended surgical treatment. Women over age 70, poor patients, and African-American or Hispanic patients were least likely to receive proper treatment. Women who were not treated by gynecologic oncologists were also less likely to receive optimal surgical care.
Surgical staging includes biopsies of the following:
- The undersurface of the diaphragm
- The omentum (the fatty layer that covers and pads organs in the abdomen)
- Sometimes lymph nodes along the abdominal aorta
An abdominal wash is performed by injecting a salt solution into the abdominal cavity to facilitate microscopic detection of cancerous cells not visible to the naked eye. The surgeon then evaluates the pelvis and abdomen and removes suspected cancer tissue. The entire affected ovary is usually removed (oophorectomy) during surgical staging if the surgeon believes it might be cancerous. The tissue is sent to a laboratory for an immediate evaluation called a frozen section diagnosis. The doctor will also examine the bowel and bladder for cancer invasion.
If the tumor is in an early stage on one ovary and a young woman wants to retain her ability to have children, the surgeon may be able to remove only the affected ovary and perform surgical staging. Chemotherapy follows in selected patients. Studies indicate that in carefully selected young patients, many can expect normal fertility afterward. However, most women with ovarian cancer are not candidates for this procedure.
The goal of surgery is to remove as much of the tumor as possible (called debulking or cytoreductive surgery) for improving symptoms and increasing the effectiveness of chemotherapy. The surgery itself is typically performed as follows:
- In premenopausal women in later stages, and in all postmenopausal women, the surgeon usually removes the uterus (a hysterectomy) and both ovaries and fallopian tubes (a bilateral salpingo-oophorectomy).
- In addition, the surgeon usually removes the omentum (omentectomy), any growths on the diaphragm and intestine, and possibly certain lymph nodes (lymphadenectomy).
If surgical staging reveals that the cancer has invaded the bowel, a portion of the intestine may have to be removed as well.
Postoperative Care. If possible, a patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:
- For 1 - 2 days after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
- As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and to hasten recovery.
- Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
- Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
- Patients are advised not to lift heavy objects (including small children), not to douche or take baths, and not to climb stairs or drive for several weeks.
- For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and form abrupt changes in hormones, particularly if the ovaries have been removed.
The patient should talk to their doctor about when they can start exercise programs that are more intense than walking. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year. Others may recover in only a few weeks.
Complications Following the Procedure. Minor complications after hysterectomy are very common:
- Women may develop minor and treatable urinary tract infections.
- There is usually light vaginal bleeding and pain after the operation, which can be well-controlled with pain medications.
More serious complications are uncommon but patients should be aware of their symptoms and call the doctor immediately if they occur:
- Infection occurs in 10 - 15% of patients, with the risk being higher with abdominal than with vaginal surgery. Symptoms might include continuing or increasingly severe pain, fever, heavy discharge, or bleeding. Antibiotics given at the time of surgery help to reduce this risk. Other risk factors for infection include obesity, a longer than normal operative time, and low socioeconomic status.
- There is a slight risk for small blood clots, usually in veins of the legs (thrombophlebitis). A sudden swelling or discoloration in the leg can indicate this condition and requires immediate medical attention.
- Other serious and even life-threatening complications, though rare, include pulmonary embolism (blood clots that travel to the lung), abscesses, perforation of the bowel, fistulas (a passage that bores from an organ to the skin or to another organ), or dehiscence (the opening of the surgical wound).
Treating Menopausal Symptoms and Premature Menopause after Hysterectomy. After hysterectomy, premenopausal women usually have hot flashes, a symptom of menopause. Symptoms come on abruptly and may be more intense than those of natural menopause. Symptoms include hot flashes, vaginal dryness and irritation, and insomnia. A significant number of women gain weight.
The most important complications that occur in women who have had their ovaries removed are due to estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease. Women have typically taken hormone replacement therapy (HRT) after surgery if their ovaries have been removed. There have been concerns however about health risks, including the risk for breast cancer and stroke, that have now limited its use. Risks in premenopausal women who have had a hysterectomy have not yet been clarified. Several nonhormonal drugs, however, can help protect both bones and heart.
After chemotherapy is completed, surgeons used to perform an exploratory procedure called second-look laparotomy. Although this procedure is the most sensitive way of detecting residual cancer that remains after chemotherapy, it has no proven impact on patient survival. Its use is restricted to patients being treated in clinical trials.
Bowel obstruction is common in ovarian cancer. Surgery can be very helpful for selected patients with this problem.
Medications
Following surgery, patients (other than those with early-stage, low-grade disease) usually have chemotherapy. Unlike surgery and radiation, which treat the cancerous tumor and the area surrounding it, drug therapy destroys rapidly dividing cells throughout the body, so it is as systemic therapy.
Ovarian cancers are very sensitive to chemotherapy and often respond well initially. Unfortunately, in most cases, ovarian cancer recurs. With treatment advances, however, more than half of women now survive 5 years or longer. Doctors are now approaching this disease as a chronic and potentially long-term illness that requires the following:
- Identifying the disease recurrence as soon as possible
- Administering treatments that are as effective as possible without causing suffering
- Partnering with the patient in determining her own best course
Standard Chemotherapy. The standard initial chemotherapy uses a combination of:
- A platinum-based drug, such as carboplatin (Paraplatin) or cisplatin (Platinol). Carboplatin is preferred over cisplatin in the combination. Carboplatin works as well as cisplatin but is less toxic and can be administered in a more convenient, outpatient regimen.
- A taxane, such as paclitaxel (Taxol) or docetaxel (Taxotere). Currently paclitaxel is the drug most often used as initial therapy in combination with a platinum drug. Docetaxel, however, is less toxic to the nervous system (but has more adverse effects on blood cell production). Taxotere is now commonly substituted for Taxol.
Paclitaxel-carboplatin chemotherapy will reduce tumor size in about 70% of women. Older women (over age 60) may benefit as much as younger ones from this regimen.
Other drugs that may prove to be useful first-line treatments are gemcitabine (Gemzar) and doxorubicin (Doxil). A third drug, topotecan (Hycamtin), is not helpful for first-line treatment for advanced ovarian cancer, according to recent studies. In an important 2006 study, topotecan following paclitaxel-carboplatin therapy did not help prolong survival, and it caused many serious side effects, including anemia and infections.
Chemotherapy Drugs Studied for Relapsed or Refractory Cancer. Unfortunately, some ovarian tumors are resistant to platinum drugs. Even in patients who respond, the disease eventually becomes resistant to the first-line drugs, and the cancer returns. Various approaches for increasing responsiveness to these drugs are being investigated. Investigators are studying two approaches for preventing relapse after remission:
- Developing more effective drug combination regimens to increase initial response rates and duration of the response.
- Developing maintenance drugs to prevent or delay relapse.
Once cancer recurs or continues to progress, several second-line chemotherapies are available or under investigation. The following lists some drugs that are being used, usually as single drugs, for relapsed or refractory cancers:
- Nucleoside analogs, including gemcitabine (Gemzar). In 2006, gemcitabine was approved as a treatment for recurrent ovarian cancer. It is used in combination with carboplatin for women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy.
- Paclitaxel or carboplatin alone or in combination. A landmark study published in the July 2003 Journal of Clinical Oncology, found that additional cycles of paclitaxel significantly delayed disease progression in women with advanced ovarian cancer.
- Pegylated liposomal doxorubicin (Doxil) is a form of standard doxorubicin (Adriamycin) that remains in the bloodstream longer, tends to spare the bone marrow, and moves selectively through the tumor. It is showing promise in clinical trials and also may have fewer toxic effects than standard doxorubicin and other drugs used for ovarian cancer. Studies show that peglyated liposomal doxorubicin is very well tolerated, with a total response rate of about 20 - 30% in patients with recurrent cancer. This compares favorably with other drugs, such as topotecan, carboplatin, and taxol.
- Topoisomerase I inhibitors, including topotecan (Hycamtin) and irinotecan (Campto).
- Topoisomerase II alpha inhibitors, including etoposide (VePesid).
- Alkaloids, including vinorelbine (Navelbine).
- Hormonal drugs: tamoxifen (Nolvadex) or anastrozole (Arimidex).
- Valspodar and capecitabine (Xeloda) are oral drugs that may help improve response to other drugs, although data are preliminary.
In addition to studying individual drugs in different combinations, investigators are looking for the optimal sequence, dosages and timing of administering them. In general, the typical regimen is as follows:
- Paclitaxel and carboplatin are administered in an outpatient clinic within several weeks of the surgery.
- Each treatment takes about 4 - 5 hours to complete.
- It is repeated every 3 weeks for a total of six times. (Each 3-week interval is known as a cycle of chemotherapy.)
Such chemotherapy is usually administered intravenously (by vein). However, an important 2006 study in the New England Journal of Medicine found that patients with Stage III ovarian cancer who received intraperitoneal chemotherapy had a significant survival advantage compared with patients who received standard intravenous chemotherapy. (Intraperitoneal chemotherapy involves administering the drugs directly into the abdominal cavity.) Patients in the intraperitoneal group did have more severe side effects than those who had intravenous chemotherapy. Researchers are continuing to investigate ways to reduce these side effects. Another 2006 study noted that intraperitoneal chemotherapy requires careful catheter insertion and maintenance, and that doctors need to be well trained to perform this procedure.
Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Some may be long-lasting. In one study of ovarian cancer survivors, 20% had long-term treatment side effects, such as gynecologic and abdominal problems. Even so, most enjoyed a high quality of life that was comparable to other cancer survivors and peers without a history of cancer.
Common side effects include:
- Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
- Diarrhea
- Temporary hair loss
- Weight loss
- Fatigue
- Depression
Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. The following list includes some of these complications and a few of their treatments:
- Anemia. Erythropoietin stimulates red blood cell production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp stays in the blood longer than epoetin alfa, so fewer injections are needed.
- Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection in selected patients.
- Liver and kidney damage.
- Abnormal bleeding (thrombocytopenia).
- Allergic reaction, particularly to platinum-based drugs.
- Rarely, secondary cancers such as leukemia.
- Between a quarter and a third of women report problems in concentration, motor function, and memory. These problems may be long-term and may be due to reductions in estrogen levels after treatments.
- Cumulative doses of anthracyclines can damage heart muscles over time and increase the risk for heart failure. An encapsulated form doxorubicin (Myocet, Doxil) may reduce the risk for toxic effects on the heart.
- Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur. Talking a corticosteroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, which is relievable with corticosteroids.
Physical Exam and CA-125 Blood Test. During treatment, the effectiveness of the chemotherapy is evaluated primarily with a physical examination and the CA-125 blood test. Falling CA-125 levels indicate effective treatment and persistently elevated levels indicate resistance to the chemotherapy.
Second Look Laparotomy. Second-look laparotomy is sometimes considered after completion of chemotherapy for patients who are participating in clinical trials.
Comparative Computed Tomography Scans. Another method for evaluating the success of chemotherapy is to compare computed tomography (CT) scans of the pelvis and abdomen before and after chemotherapy to check the size of any residual tumors that persisted after the original surgery. CT scanning is not always required, however.
Positron Emission Tomography ). Positron emission tomography (PET) scans have no proven role in the management of patients with ovarian cancer. More study is needed to determine their utility in diagnosing relapsed disease.
Any patient with ovarian cancer is a candidate for clinical trials. In addition to testing high-dose or combinations of chemotherapy, drugs with unique actions are being investigated.
Anti-angiogenesis drugs. Angiogenesis, the formation of new blood vessels that feed the growth of a cancerous tumor, is a critical process in the spread of ovarian cancer. Drugs that block this process are under investigation for ovarian cancer. Some of these drugs target vascular endothelial growth factor (VEGF), a protein involved in tumor cell growth. Results of a phase II study, presented at the 2007 meeting of the American Society of Clinical Oncology, indicated that the anti-angiogenesis drug aflibercept (VEGF-TRAP) may benefit patients with epithelial ovarian cancer who are resistant to platinum-based chemotherapy. Such drugs include thalidomide, gefinitib (Iressa), and carboxyamido-triazole (CAI).
Aromatase inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many body tissues. Aromatase inhibitors are used for treatment of estrogen-sensitive breast cancer. These drugs include anastrozole (Arimidex) and letrozole (Femara). Studies indicate that they may provide an alternative to chemotherapy for types of ovarian cancers that are responsive to anti-estrogen hormonal therapy.
Multiple signal transduction regulators. Phenoxodiol is an multiple signla transduction regulator that is being developed as a broad-spectrum anti-cancer drug. It is currently being evaluated in phase III clinical trials, in combination with other drugs, such as carboplatin, for its ability to shrink tumors or stop tumor growth in women with ovarian or fallopian cancer who have failed other forms of chemotherapy.
HER Dimerization Inihibitors. Pertuzumab (Omnitarg) is the first of a new class of drugs called HER dimerization inhibitors. It is designed to inhibit tumor growth for tumors that express the HER2 receptor protein. Pertuzumab is currently in phase II trials in combination with gemcitabine for women with platinum-resistant ovarian, peritoneal, or fallopian cancer.
Immunotherapy. Several therapies under investigation use the body's immune response to attack ovarian cancer cells. Experimental immunotherapies include vaccines designed to treat -- not prevent -- cancer. Some of these vaccines use specially designed antibodies (called monoclonal antibodies, or MAbs) to boost the immune responses against tumor-associated factors, such as CA125 or HER-2/neu. Vaccine therapy is still in early-stage clinical research and is being studied in combination with various chemotherapy drugs.
Epothilones. Epothilones are a new class of anti-cancer drugs that are similar to taxanes (paclitaxel) but are more potent. One of these drugs, ixabepilone (BMS-247550), is being studied for ovarian cancer.
Radiation Therapy
Radiation therapy is not typically used in ovarian cancer. This is because radiation would need to be given to the entire abdomen and pelvis, increasing its toxicity. Radiation is sometimes useful to treat isolated areas of tumor that are causing pain and are no longer responsive to chemotherapy.
Resources
- www.cancer.gov -- National Cancer Institute
- www.cancer.org -- American Cancer Society
- www.aacr.org -- American Association for Cancer Research
- www.asco.org -- American Society of Clinical Oncology
- www.plwc.org -- People Living with Cancer
- www.ovarian.org -- National Ovarian Cancer Coalition
- www.ovariancancer.org -- Ovarian Cancer National Alliance
- www.sgo.org -- Society of Gynecologic Oncologists
- www.wcn.org -- Women's Cancer Network
- www.ovariancancer.com -- The Gilda Radner Familial Ovarian Cancer Registry
- www.cancer.gov/clinicaltrials -- Find clinical trials
References
Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.
Bristow RE, Santillan A, Diaz-Montes TP, Gardner GJ, Giuntoli RL 2nd, Meisner BC, et al. Centralization of care for patients with advanced-stage ovarian cancer: a cost-effectiveness analysis. Cancer. 2007 Apr 15;109(
:1513-22.
Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007 Jan 15;109(2):221-7.
Goff BA, Matthews BJ, Larson EH, Andrilla CH, Wynn M, Lishner DM, et al. Predictors of comprehensive surgical treatment in patients with ovarian cancer. Cancer. 2007 May 15;109(10):2031-42.
Lacey JV Jr, Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schatzkin A, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst. 2006 Oct 4;98(19):1397-405.
[No authors listed] An experiment in earlier detection of ovarian cancer. Lancet. 2007 Jun 23;369(9579):2051.
Smyth JF, Gourley C, Walker G, MacKean MJ, Stevenson A, Williams AR, et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res. 2007 Jun 15;13(12):3617-22.
10/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
Nica
Heine
7 For All Mankind
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