FAQs About Ovarian Cancer
Ovarian cancer may affect women of any age group, although it is more common in post-menopausal women. The type of ovarian cancer which occurs in adults is usually of the "epithelial" variety, a term which refers to the fact that this tumor starts in the surface epithelial covering of the ovary.
Other types of ovarian tumors may develop, depending upon which type of cell gives rise to the cancer. For instance, younger women may develop ovarian "germ cell" tumors (which start in young cells similar to the eggs contained within the ovary), and older women may develop ovarian stromal cell tumors (like granulosa cell cancer) which start in the supporting tissue (stroma) contained within the ovary.
It is important to distinguish between these various types of ovarian tumors, since the treatment approach may differ. In the following information, the term "ovarian cancer" will be used to describe the most common type of tumor seen in adults (namely, the epithelial variety).
Who is at Risk for Epithelial Ovarian Cancer?
Approximately 1 in 70 women will develop epithelial ovarian cancer each year in the United States, translating into about 27,000 new patients per year. Factors which are associated with lower risk of ovarian cancer include a history of birth control pill use, pregnancy, or breast feeding. The most important factor associated with increased risk for developing this tumor is a strong family history of ovarian and/or breast cancer, especially if these diseases occur at a young age and involve close family members (like a mother or sister, also known as "first degree relatives"). If you have a strong family history of these kinds of cancers, you may wish to take advantage of genetic counseling opportunities in your area (see section below entitled "Inheritance and Ovarian Cancer"). However, it is important to realize that most patients who develop ovarian cancer have no obvious risk factors.
Early Warning Signs
Unfortunately, many patients with ovarian cancer experience no early warning signs. This is because the tumor may spread beyond the ovary to involve other areas within the pelvis and abdomen at a time when it is too small to be detected by the pelvic examination. Occasionally, the tumor is detected at an early stage by pelvic exam (see below for staging), sometimes in the setting of pelvic pain. More commonly, however, patients with ovarian cancer come to medical attention because of abdominal discomfort and bloating (often due to the presence of tumor outside of the ovary).
How are Patients usually Diagnosed?
Once a pelvic mass is discovered by exam, your physician may order special tests such as a pelvic ultrasound to further evaluate the mass. If the ultrasound confirms the possibility of an ovarian tumor, a surgical procedure (oftentimes an exploratory laparotomy) is often performed to remove the mass for examination by the pathologist. If the mass appears to be malignant, it may be necessary to perform removal of the ovaries and fallopian tubes ("bilateral salpingo-oophorectomy") and removal of the uterus ("hysterectomy"). If the tumor has extended beyond the ovary to involve other sites in the pelvis and abdomen, an attempt is made to remove as much tumor as possible ("debulking"). This is done because patients who have only small amounts of tumor remaining tend to respond more favorably to post-operative treatments such as chemotherapy. During the operation, the surgeon may take small amounts of tissue from many different areas of the abdomen and pelvis ("biopsies") in order to determine the exact locations of the tumor. This will help to determine your tumor stage and guide further treatment decisions.
Staging
Patients may be diagnosed with one of four different stages of ovarian cancer:
- Stage I Tumor confined to the ovary or ovaries.
- Stage II Tumor involving other sites in the pelvis.
- Stage III Tumor involving the upper abdominal cavity or lymph nodes within the abdomen or pelvis.
- Stage IV Tumor which has spread beyond the abdominal cavity, or which involves the insides of organs such as the liver or spleen.
What Needs to be Done after the Operation?
Approximately 30% of patients will be diagnosed with stage I or II tumors, and 70% of patients will have stages III or IV disease. Most patients with epithelial ovarian cancer have tumors that cannot be completely removed by surgery alone. Even in situations where all of the obvious tumor has been removed, there are often microscopic areas of tumor remaining which can grow back again if not treated. That is why the majority of patients with ovarian cancer will require some form of chemotherapy after the operation in an attempt to destroy any remaining tumor cells. Under rare circumstances, certain patients with early stage disease may not require further treatment. However, only your oncologist can advise you as to whether this approach is appropriate for your situation.
Chemotherapy for Epithelial Ovarian Cancer
The present standard of care for treatment of patients who are felt to be appropriate candidates for post-operative chemotherapy is a combination of two kinds of chemotherapy agents. One kind is called the "taxanes" and includes drugs such as Taxol™ (paclitaxel) and Taxotere™ (docetaxel). The other kind is called "platinum" analogs and includes drugs such as carboplatin and cisplatin. A commonly used regimen is comprised of Taxol™ and carboplatin, often administered intravenously in the outpatient clinic once every 3 weeks for a total of 6 treatments (also known as "cycles"). Other combinations which have been used include Taxotere™ and carboplatin, or Taxol™ and cisplatin. These all represent active regimens, and the ultimate choice depends upon your physician's preference, as well as whether you are participating in a clinic trial (see below). You should discuss the details of chemotherapy, including side effects, with your physician.
Effectiveness of Chemotherapy
Over 70% of patients who receive chemotherapy will experience a beneficial reduction in the size of residual tumor, oftentimes associated with a drop in the level of a blood test known as CA-125. CA-125 is a substance made by ovarian cancer cells, and its blood level drops as the tumor is destroyed. Unfortunately, many (but not all) patients experience regrowth of their tumor at some point in the future. At that time, retreatment with additional chemotherapy is often required, although obtaining good control of the tumor may be more difficult. This is due to the fact that recurrent tumors develop a certain amount of resistance to the effects of chemotherapy (a condition known as "drug resistance"). Several options are available for managing recurrent ovarian cancer, including retreatment with taxanes or platinum agents, or the use of different agents such as tamoxifen, topotecan, Doxil™, or etoposide. Your oncologist is in the best position to decide which of these agents would be most appropriate for your situation.
Clinical Trials
The realization that many patients with ovarian cancer experience recurrence of their tumor has lead to the need for better treatment approaches. In this regard, clinical trials testing new treatments for ovarian cancer may be available for patients who wish to participate and who meet the eligibility criteria. It is important to remember, however, that there is currently (as of March 1999) no treatment approach for patients with newly-diagnosed disease that is convincingly better than the standard chemotherapy described above. That is why clinical trials are called "investigational." Nevertheless, new treatments which are studied in the setting of clinical trials may eventually prove to be better than standard approaches. You or your physician may wish to discuss the possibility of clinical trial participation with our staff, who would be happy to assist you. Also, an excellent web site which further describes the importance of clinical trial participation may be found at the following address:
http://cancertrials.nci.nih.gov/.
Selected references
Cannistra SA. Medical progress: Epithelial cancer of the ovary. New England Journal of Medicine 1993; 329:1550-1559.
Cannistra SA. Paclitaxel in ovarian cancer: How can we make it better? J Clin Oncol 1994; 12:1743-1744.
Cannistra SA. "Cancer Defeated": Not if, but When. Journal of Clinical Oncology 1997; 15:3297-3298.
Tai YT, Lee S, Niloff E, Weisman C, Strobel T, Cannistra SA. BAX protein expression and clinical outcome in epithelial ovarian cancer. Journal of Clinical Oncology 1998; 16:2583-2590.
Useful Information about Inheritance and Ovarian Cancer
Is ovarian cancer inherited?
The majority of ovarian cancers are caused by unknown factors. About 5% of ovarian cancers are caused by inherited factors (e.g., abnormalities in genes known as mutations which may be inherited from either parent). In this situation, a woman may be born with (inherits) a mutation in a gene that predisposes her to the development of ovarian cancer. At least two patterns of hereditary ovarian cancer have been described. In the first, a patient with ovarian cancer may have other family members with breast cancer, ovarian cancer, or even both tumors in the same individual. This is known as the breast/ovarian cancer syndrome. In the second, an ovarian cancer patient may have family members with a variety of other tumors (see below), including colorectal cancer and endometrial (uterine) cancer. This is sometimes referred to as the Lynch syndrome II.
What genes are involved?
Most hereditary ovarian cancers occur in families with the breast/ovarian cancer syndrome and are associated with inherited mutations in one of two genes known as BRCA1 and BRCA2. BRCA1 mutations account for the majority of cases of inherited ovarian cancer (50%-70%), while BRCA2 mutations are less common (15-25%). When a parent has a mutation in a gene such as BRCA1 or BRCA2, there is a 50% chance of passing on the mutation to each of his or her children.
Families with the Lynch syndrome II usually include several individuals who develop bowel (colon or rectal) cancer, often before age 50. These bowel tumors are usually not associated with polyps and are therefore sometimes called "hereditary non-polyposis colon cancer" (HNPCC). Other tumors which may affect members of these families include endometrial, ovarian, stomach, small bowel, bile duct, and urinary tract cancers. Lynch syndrome II is caused by a mutation in one of several different genes known as mismatch repair genes. The two genes responsible for the majority of mutations found are known as MSH2 and MLH1. Less commonly mutations can be found in the PMS1, PMS2 and MSH6 genes. In at least one third of families with the Lynch syndrome II, no identifiable mutation is found.
How do I suspect that breast or ovarian cancer in my family might be inherited?
Some situations increase the likelihood (but do not necessarily mean) that an inherited form of cancer may exist in a family:
- Breast and/or ovarian cancer occurring in at least three close relatives.
- Breast and/or ovarian cancer occurring at an early age (before menopause).
- Breast and ovarian cancer occurring in the same family member.
- Men in the family with breast cancer (suggests BRCA2 mutation).
Family members with bowel cancer at an early age (before 50), endometrial cancer, or other Lynch syndrome associated cancers (see above).
What is genetic testing?
Scientists are now able to look for mutations in genes with a blood test. This genetic test can sometimes determine if an individual has an inherited form of ovarian cancer. If a mutation is found, other family members can learn if they have inherited the same mutation and therefore have an increased risk for cancer. It is preferable to begin the process of genetic testing in a patient already affected with cancer, since a specific mutation found in that individual would make the search for the same mutation in other family members much easier. Several types of mutations in BRCA1 and BRCA2 are more common in certain ethnic groups. Your physician will be able to provide you with more details as appropriate.
What are my options if I have a BRCA1 or BRCA2 mutation?
A woman with a mutation in BRCA1 or BRCA2 has an increased chance of developing breast cancer and/or ovarian cancer. There are several strategies one can use to try to prevent cancer from occurring, or to increase the chance of detecting it early. While no method for prevention or early detection has yet been proven to be completely effective, options include:
Increased surveillance (cancer screening). Breast cancer may be detected with surveillance measures such as breast self-exams, mammograms, and breast exams performed by your doctor. Likewise, pelvic ultrasounds and a blood test called CA-125 are sometimes used in an attempt to detect ovarian cancer at an early stage. Whether these surveillance measures can result in early cancer detection and lead to improved survival in patients with BRCA1 or BRCA2 mutations is unknown.
Prophylactic (preventive) surgery. This approach involves removing the breasts and/or ovaries before cancer can develop. It is important to remember, however, that it is not possible to remove all of the breast tissue, and a small number of women can still develop breast cancer even after the surgery. Likewise, a type of ovarian cancer starting inside the abdomen can occasionally develop, even in patients whose ovaries are prophylactically removed. The impact of these procedures on survival remains uncertain, although consideration of prophylactic surgery in selected women is reasonable. The pros and cons of this approach need to be carefully discussed between you and your physician.
Chemoprevention. A recently published national trial (the Breast Cancer Prevention Trial) demonstrated that women who took a medication called tamoxifen for five years reduced their risk of developing breast cancer by 50% compared to women who took a placebo. The second national breast cancer prevention trial, known as the STAR study, will compare tamoxifen to a newer tamoxifen-like drug called raloxifene, in order to determine which drug is superior in preventing breast cancer. It is not yet known whether these medications reduce the risk of developing breast cancer in BRCA1 and BRCA2 mutation carriers. Other research has shown that women who have used birth control pills have a lower incidence of developing ovarian cancer (a recent study suggests that this may also be the case for women who carry a BRCA1 mutation).
What are my options if I have a Lynch Syndrome associated mutation?
Cancer Screening. Individuals with a Lynch Syndrome mutation are at especially high risk for developing colorectal cancer, although the risk for other tumors such as those involving the endometrium (uterus), ovaries, and stomach is increased as well. A procedure known as colonoscopy should be frequently performed to detect colon cancer and/or to remove precancerous lesions in patients with the Lynch syndrome. Screening tests for cancers at other sites are of uncertain value and are beyond the scope of this section. Your physician will be able to provide you with more details as appropriate.
References
Burke W, Daly M, Garber J et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II BRCA1 and BRCA2. Cancer Genetics Studies Consortium. JAMA 277:997, 1997.
Couch FJ, Weber BL. Breast cancer. In Vogelstein B, Kinzler KW (eds), The Genetic Basis of Human Cancer. New York: McGraw Hill, 1998.
Couch FJ, DeShano ML, Blackwood MA, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. NEJM 336:1409, 1997.
Ford D, Easton DF, Bishop DT, et al. Risks of cancer in BRCA-1 mutation carriers. Lancet 343:692, 1994.
Struewing JP, Hartge P, Wacholder S et al. The risk of cancer associated with specific mutations of BRCA-1 and BRCA2 among Ashkenazi Jews. NEJM 336:1401, 1997.
Understanding how ovarian cancer cells spread (metastasize): Many gynecologic tumors spread beyond the pelvis to involve the abdominal lining (peritoneum) and lymph nodes. Dr. Cannistra and his team were the first to demonstrate the importance of the CD44 molecule in this process and has developed ways to prevent the spread of ovarian cancer in the laboratory using antibodies against this protein. More recently, he has shown that another class of proteins called beta-1 integrins are involved in ovarian cancer attachment to the peritoneal lining (Gynecologic Oncology, 1999, in press). Through Dr. Cannistra's efforts, the Beth Israel Deaconess Medical Center and the Harvard Medical School have pioneered the concept that adhesion proteins can function as "molecular velcro" in ovarian cancer spread. Future work will concentrate on developing clinical agents that interfere with proteins like CD44 and thereby prevent metastasis within the abdomen. See references Strobel97, Cannistra95a, Cannistra95b, Cannistra94a, and Cannistra93 for further information.
Understanding why tumor cells commonly develop resistance to chemotherapy: The development of resistance to chemotherapy drugs is a major problem that limits the usefulness of many agents such as paclitaxel (TaxolTM ) and carboplatin. Dr. Cannistra and his team have recently identified a new set of proteins that chemotherapy uses in order to effectively kill cancer cells. On such protein is called BAX, and we have recently learned that this molecule enhances the activity of TaxolTM in the laboratory. Importantly, Dr. Cannistra has recently shown that tumors containing low levels of BAX generally do not respond well to chemotherapy, suggesting a potentially important role for this protein in determining how well chemotherapy will work in a given patient. More recently, he has developed a way to express high levels of BAX inside of ovarian cancer cells through an adenoviral gene therapy approach, resulting in profound and selective killing of ovarian cancer cells in the laboratory (Cancer Research, 1999, in press). Although this strategy is not yet ready for clinical use, it provides proof that this or a similar approach may someday become a valuable part of therapy for patients with gynecologic tumors. Dr. Cannistra's most recent efforts are directed at identifying new genes which cause drug resistance using powerful genetic approaches such as SAGE and microarray technology. See references Strobel98, Strobel96, and Cannistra94b for further information.
Developing novel chemotherapy regimens for the treatment of patients with gynecologic cancers. Dr. Cannistra and his team at the Beth Israel Deaconess Medical Center are committed to developing new therapies for patients with gynecologic tumors, with a special focus on ovarian cancer. As an example of these efforts, we have developed a novel first-line, multiagent regimen using a combination of four drugs (Carboplatin, TaxolTM , Etoposide, and Cyclophosphamide, with G-CSF support) and have shown this to be a well-tolerated and highly active treatment in ovarian cancer. Current research efforts are underway to develop a novel combination regimen which includes a new drug (gemcitabine) shown to enhance the effectiveness of carboplatin and TaxolTM in the laboratory (please see
Clinical Trials section for more information). This trial is potentially appropriate for patients with newly-diagnosed high-risk ovarian and primary peritoneal serous cancers. Dr. Cannistra is also developing regimens for relapsed disease involving drugs such as Taxotereä and a novel compound design to inhibit angiogenesis (Please see
Clinical Trials).
Understanding how genes and proteins predict for tumor behavior and treatment success: Dr. Cannistra has established a large tumor bank and clinical database as part of his efforts in gynecologic cancer research. Utilizing the expertise of a sophisticated genomics core at the Harvard Institutes of Medicine (www.bidmcgenomics.org), his team is systematically obtaining a "fingerprint" of genes that might predict for tumor resistance or a low chance of benefit with conventional treatment approaches. The technique used for this work is known as microarray gene profiling and has become a powerful tool in better understanding how cancers behave. Our program is also performing a similar analysis evaluating urinary proteins in order to determine whether a protein "fingerprint" in urine might someday prove to be a better screening test for ovarian cancer. Through these efforts, it is hoped that someday we will be able to individualize therapy so that it is more effective against the patient's own tumor, as well as possibly detect ovarian cancers at an early and more curable stage.