Dr. Deborah Armstrong
In the Spotlight

Dr. Armstrong is an Assistant Professor of Oncology at the Johns Hopkins University School of Medicine and is the director of the Johns Hopkins Oncology Center’s high dose chemotherapy/ stem cell transplant program for breast cancer and ovarian cancer.

What have been the major accomplishments in ovarian cancer research over the past five years?

The most important accomplishment was the introduction of anti-cancer drugs called taxanes such as Taxol and Taxotere into initial chemotherapy. This has improved the survival rate for patients with advanced ovarian cancer. Another significant achievement was the recognition of the importance of aggressive surgery to remove ovarian cancer. Finally, the identification of patients at high risk for ovarian cancer due to a family history was an important step in ovarian cancer research. However, more data is needed to evaluate and identify other risk factors and to learn how best to manage these patients.

How have these accomplishments impacted you as a physician and your patients?

The standard therapy for ovarian cancer patients has changed significantly. The average patient five to ten years ago and the average patient today receive quite different treatments. We have been incorporating new investigational treatments such as new drugs into initial therapy. Progress has occurred quite rapidly, and information has filtered down to the clinical level quickly, considering the low numbers of ovarian cancer cases.

What do you tell a patient who is concerned about ovarian cancer because of a family history?

Patients usually come to the clinic with a family history of breast cancer, and ovarian cancer is not on their radar. Ovarian cancer is relatively rare, so patients usually have more knowledge of and experience with breast cancer. However, breast and ovarian cancers are quite different from each other. They don’t share the same screening strategies or treatments. It is important for patients to recognize the significance of ovarian cancer risk because screening for ovarian cancer is not proven effective. Because of this, prevention is critical.

Certain prevention strategies are discussed with patients at increased risk for ovarian cancer. Good data indicate that prolonged use of oral contraceptives decreases the risk of ovarian cancer. In addition, oophorectomy is a surgical procedure to remove the ovaries before cancer develops. This procedure can be performed through laparoscopy (a surgical procedure requiring only a small opening in the abdomen). Oophorectomy is a bit controversial because there is not the same amount of convincing data that oophorectomy decreases ovarian cancer risk as there is that mastectomy decreases breast cancer risk. Furthermore, removal of the ovaries does not completely reduce the risk because the surface of the ovaries, called the peritoneum, is continuous with the surface of the abdominal cavity. Cancer that occurs on this surface is called primary peritoneal cancer and can still occur after the ovaries have been removed. Also, in pre-menopausal women, removal of the ovaries causes premature menopause. Hormone replacement therapy may be necessary if a woman wishes to reduce the symptoms of menopause. However, hormone therapy may subsequently increase breast cancer risk. This is not a comfortable decision for patients who are already at high risk for breast cancer.

Several screening procedures are recommended for women at increased risk of developing ovarian cancer: physical exam, including pelvic examination; imaging through transvaginal ultrasound; and biochemical (blood) tests. However, the ability to discern small masses through physical examination is limited. Sonograms produce good images, but there is a natural tendency for the ovaries to form cysts due to ovulation in pre-menopausal women. These normal cysts are sometimes quite difficult to distinguish from pre-cancerous lesions. Repeat sonograms are needed to follow up on possibly abnormal findings. After menopause, women do not ovulate, so they should no longer develop these natural cysts. Theoretically, then, imaging should be more effective on post-menopausal women. However, we have learned that post-menopausal women develop some cysts. Another type of imaging, called color Doppler, looks at blood flow. This may be helpful during the early stages of the cancer.

Relying on these screening tests, many unnecessary surgeries would be performed because of their limitations. Using blood tests to look for tumor markers in the blood (biochemical substances that may suggest the presence of cancer) presents further complications. For example, the blood test for CA-125 is not very sensitive and therefore can miss many cases. About 80-85% of patients with advanced ovarian cancer that has spread to other parts of the body have elevated CA-125. It is also not specific so that many non-malignant conditions such as endometriosis, pelvic inflammatory disease, tubal ovarian abscesses that lead to infection, and even certain phases of the menstrual cycle can elevate CA-125. Furthermore, appendicitis, liver diseases, and other conditions that affect the lining of the abdominal cavity can cause CA-125 elevations. In post-menopausal women, fibroids can increase CA-125 levels. Attempts to set certain thresholds within which to consider ovarian cancer diagnoses have not been successful since many women that have been diagnosed have CA-125 levels outside of the established ranges. Now, the use of combinations of tumor markers is being considered to increase the accuracy of detection.

What do you think should be the priorities in ovarian cancer research in the upcoming years?

The future of ovarian cancer research lies in understanding the molecular changes that lead up to cancer formation. When most patients come to the clinic, they usually already have ovarian cancer. We do not know what specifically happens in the ovaries before cancer develops. In colon cancer, we know that a polyp frequently forms before cancer develops. In cervical cancer, we can detect pre-cancerous changes through a Pap smear. However, we don’t have the same situation in ovarian cancer because we don’t know what to look for. During the next 5 to 10 years, we will probably see the development of very powerful molecular technologies that allow us to see the sequence leading up to the development of cancer and learn what pre-malignant changes to look for. The key may not be looking at the ovaries themselves, but looking in the blood instead.

Furthermore, we need to explore what factors that put people at risk can be manipulated. If we knew more about the effects of lifestyles, hormones, environmental exposures, dietary factors, or even the enzymes involved in metabolism and their products, we could predict who’s at risk for ovarian cancer based on these factors and have red flags for more aggressive screening. A vast majority of patients do not have a family history of ovarian cancer. Because ovarian cancer is rare, family history is limited in its ability to identify risk. The ability to know and recognize these various factors and the pathway of ovarian cancer development will be powerful in ovarian cancer screening, detection, and treatment.