We know that all cancers have a genetic basis, but not all cancers are inheritable. General population-based screening and risk assessment, in which we evaluate an individual’s genetic profile and identify who is at risk for a specific cancer and then intervene before there is a cancer, is going to become a reality.
—David Fishman, MD
Fifteen years ago, David Fishman, MD, launched the National Ovarian Cancer Early Detection Program as part of the National Cancer Institute’s Early Detection Research Network. The goal of the research effort was to develop methods to accurately detect ovarian cancer while it was still confined to the ovary and potentially curable. In 2013, Dr. Fishman renamed the program the Mount Sinai Ovarian Cancer Risk Assessment Program to reflect advances, especially in genetic screening, that can be utilized to combat this usually fatal cancer.
“We are not able to detect early-stage ovarian cancer, but we can identify people at risk,” said Dr. Fishman. This year, about 22,000 women in the United States will be diagnosed with ovarian cancer, and 14,270 will die from the disease.1 Until more effective therapies are discovered to improve survival, determining effective preventive strategies in high-risk women may be a more attainable goal.
The ASCO Post talked with Dr. Fishman, Director of the Mount Sinai Ovarian Cancer Risk Assessment Program and Professor and Fellowship Director in the Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Medicine at the Icahn School of Medicine at Mount Sinai in New York, about the advances in accurately evaluating risk for ovarian cancer, the importance of screening both women and men for inheritable syndromes that can lead to a variety of cancers, and the hope for more effective preventive strategies.
Assessing Ovarian Cancer Risk
What are the known risk factors for developing ovarian cancer?
The majority of women who develop ovarian cancer do not have any identifiable risk factors. Only about 20% of women who develop ovarian cancer have known risk factors, which include a personal or family history of malignancies associated with an increased risk of ovarian cancer, such as breast cancer, or recognized inherited cancer syndromes, such BRCA1 and BRCA2 mutations, Lynch syndrome, and Cowden syndrome gene mutations.
As we become more sophisticated in genetics and in the analysis of genetic linkage of gene mutations, I’m afraid we are going to have even more individuals at increased risk of developing ovarian cancer than we currently know. It is unfortunate that we really don’t even know if ovarian cancer starts in the ovary. It may start in a fallopian tube, so there are a lot of unknowns about what puts a woman at risk for this disease.
About the Program
What are the components of the Ovarian Cancer Risk Assessment Program?
Advances in our understanding of genetics and the linkage of gene mutations to disease have allowed us to more accurately identify people at risk for ovarian cancer. In the past, we just knew about the link between BRCA1 and BRCA2 mutations and Lynch syndrome and the development of breast and ovarian cancers. Now, we know that there are over 21 mutations associated with an increased risk of these diseases. As we discover more gene mutations the numbers of those at risk will rise.
Our program has two arms. One is a very strong basic science component to understand the biology of ovarian cancer and the process of metastasis. The other arm is a clinical component based on classic genetics in which a team of board-certified genetic counselors and geneticists validate gene mutations associated with risk and perform formal pedigree analysis to identify women at risk for ovarian cancer as well as family members at risk for not just ovarian cancer but for other cancers as well.
With this program, any individual who is currently healthy but at increased risk for ovarian cancer can seek more intensive cancer surveillance and preventive bilateral salpingo-oophorectomy surgery if appropriate. We haven’t given up on finding a cure, but, to me, preventing ovarian cancer from ever taking place will be a much better strategy than treating it after it occurs.
Who is eligible for the program?
Risk can be perceived or real, and since 80% of women who develop ovarian cancer have no known identifiable risk factors, I would never turn away any woman who wants to be assessed for the disease. We often see women who have no identifiable risk factors but want to utilize our multidisciplinary team of experts to become educated about their potential risk factors, early surveillance strategies, and what they can do to prevent the cancer.
What are you investigating in new methods for the early detection of ovarian cancer?
Right now we are using nonresearch tools in patient care. By using tests that are currently commercially available we have the ability to identify those individuals that have known genetic mutations predisposing them to ovarian cancer. For younger women desiring to maintain fertility, we can prescribe birth control pills, which can decrease the risk of ovarian cancer by 50%. For women who have completed their childbearing years, we can offer a prophylactic oophorectomy.
We are investigating the effectiveness of transvaginal contrast enhanced ultrasound in detecting preclinical stages of ovarian cancer, but the technology is still not sensitive enough to pick up aberrant, precancerous cells the way a Pap smear can detect dysplasia. So even though we have pioneered some advances with intravenous contrast, the issue with transvaginal sonography remains that by the time we see a lesion it is often late-stage cancer.
We are also researching how ovarian cancer avoids immune surveillance and how to turn on the immune system to defend the body against the cancer. We are focusing on select microRNAs that can activate the immune system to identify malignant cells vs healthy cells, but this work is in its infancy.
Ultimately, we would like to prevent cancer, because we do not have drugs that can cure patients. I would love to see 90% survival in this disease, but it is detected too late and survival rates are terrible. Women who are diagnosed with advanced disease have a 5-year survival rate at best approaching 45%. Our newer chemotherapies have had some impact but not nearly enough.
While I believe the future in more effective treatment is going to be in advances in biologics and combinations of drugs that target the specific unique pathways of how cancer spreads, we do not have anything like that now.
What do you envision for more effective strategies against ovarian cancers?
I would love to see a competent immune system that could defend the body against errant cells that become malignant. I think it is the concept of immune regulation that will be the future in cancer care.
Advances in genetic screening will also improve cancer outcomes. We are in the infancy of identifying genes that are associated with the development of cancers, and I think that the sophistication required to stay on top of this evolving technology is going to mandate implementation of a new specialty of board-certified cancer geneticists to interpret the data.
This type of specialization does not exist today, but I believe it will in the near future. We know that all cancers have a genetic basis, but not all cancers are inheritable. General population-based screening and risk assessment, in which we evaluate an individual’s genetic profile and identify who is at risk for a specific cancer and then intervene before there is a cancer, is going to become a reality.
The sophistication we see coming in precision diagnostics and in our understanding of the immune system will result in cancers becoming preventable, and the key will be in immunization and having the immune system turned on to protect us against cancer. ■
Disclosure: Dr. Fishman reported no potential conflicts of interest.
1. American Cancer Society: What are the key statistics about ovarian cancer? Available at www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-key-statistics. Accessed September 19, 2014.