This is the sixth article in a series of stories related to cancer survivorship. Look for the symbol on the left in an upcoming issue for the next article in the series.
When Ovarian Cancer Returns Years Later
In 1995, when Susan Lowell Butler was unlucky enough to be diagnosed simultaneously with advanced ovarian and advanced breast cancer at age 52, doctors began to talk about her "tumor burden." Of all the medical jargon she was hearing as a patient, this phrase stood out. "I kept thinking of the 'tumor burden' as a backpack on my back," she recalled. But those doctors were able to rid her body of the tumors, and, in the process, she learned more than she ever wanted to know about being a patient with cancer.
When she emerged from her treatments alive, Butler used this knowledge to help women with ovarian cancer. She co-founded the Ovarian Cancer National Alliance, an advocacy organization, and has served on many advisory boards for NCI and NIH. When President Obama visited the NIH campus last year, Butler was there as the official greeter.
But, unfortunately, her ovarian cancer came back, as this cancer so often does. During a routine colonoscopy 2 years ago, doctors discovered a tumor wrapped around her colon. "Recurrence is the norm in ovarian cancer," Butler said. "Cures are not the norm."
Her treatment options, however, have changed since her original diagnosis. In 1995 she enrolled in a clinical trial sponsored by NCI that was testing three types of chemotherapy. "The thinking with this very intense trial was that killing the cancer cells by several different ways would give people in the trial their best chance at survival," said Butler.
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Today, clinical trials are increasingly testing drugs that target specific changes in cancer cells. Butler said that her tumor tissue is being tested to try to find a match with one of these agents. Another change over the last decade has been the introduction of more tools for managing the side effects of treatment, which has improved the quality of life for many patients.
"Since I was first diagnosed, a great many new drugs have become available, and these have allowed a lot of women with the disease to live a lot longer than they did in the 1990s," said Butler. At the same time, medications that can reduce or eliminate nausea and other side effects are available and covered by most insurers, she added.
"Fifteen years after Susan Butler's diagnosis, the progress in ovarian cancer has been astronomical," said Dr. Elise Kohn of NCI's Center for Cancer Research, who co-led the trial that helped Butler in 1995. "The number of investigators in the field has increased dramatically, and there is more funding, which has improved the quality and quantity of life for our patients."
The challenge now, Dr. Kohn continued, is to identify the most promising targeted therapies and learn how to use them. Biological markers are needed to identify patients who are likely to benefit from a particular treatment and patients who should be spared the time and expense of treatments that are unlikely to help them.
"The whole field is very excited about targeted therapies," agreed Dr. Deborah Armstrong, an ovarian cancer researcher at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. "In all cancers, the biggest advances have been coming from targeted therapies, and, unless there's a whole new family of chemotherapy drugs, I don't think we're going to be able to push the envelope there."
Of course, to develop targeted drugs researchers need to understand the genetic changes in the disease, and this information continues to emerge from the lab. (See the related highlight in this issue.) In the coming months, investigators participating in The Cancer Genome Atlas project expect to publish a genomic analysis of hundreds of ovarian tumors and related health information from the tumor donors.
In the meantime, drugs that target several pathways have shown promise in recent reports from clinical trials. The VEGF pathway, for instance, plays a role in the growth and survival of ovarian cancer. Anti-VEGF drugs, like bevacizumab (Avastin), are being tested alone and in combination with chemotherapy with some encouraging results.
Another approach has been to target pathways involved in repairing damaged DNA. Some ovarian cancers have mutations in the genes BRCA1 and BRCA2, which play a role in repairing DNA. Drugs that target the effects of these changes, called PARP inhibitors, have yielded positive results in clinical trials.
"PARP inhibitors clearly have activity in tumors that harbor inherited mutations in BRCA genes," said Dr. Armstrong. "But these drugs look like they may also work in patients with non-inherited (sporadic) ovarian cancers, so that's really exciting." There is also some excitement around drugs that target folate receptors, she noted.
For a disease that is usually diagnosed in the later stages, earlier detection is a priority for researchers. But even though many women have cancer beyond the ovaries at the time of diagnosis, doctors are still able to get the vast majority of these patients into remission, noted Dr. Armstrong.
"We are trying to understand the early changes in the disease that will lead us to early detection," said Dr. Kohn. "We'd like to get to the point where breast cancer is; where we identify the disease through techniques like mammography or MRI."
Why the disease comes back is not well understood. One theory is that cells with the properties of stem cells—so-called cancer stem cells—may resist standard treatments and then eventually give rise to new tumors. This hypothesis is being tested for a number of cancers.
In another new area, researchers have identified changes in how RNA is processed in ovarian cancer cells compared with normal cells. These changes could be associated with outcomes in patients with ovarian cancer, researchers at the University of Texas M. D. Anderson Cancer Center reported recently. "We are continuing to make substantial progress in understanding the regulation of the cell's machinery for processing RNA," noted Dr. Anil Sood, who led the study.
The Path Forward
"This disease is proving to be a very complex cancer," said Butler, who now directs the D.C. Cancer Consortium. "All cancers are complex, but this one is particularly devilish." She argues that, along with more research, getting patients to enroll in clinical trials is critical for progress.
"If you want to move the research along then you need to increase participation in clinical trials," she said. "Otherwise you won't find out the efficacy of what you're testing and you won't get the medicines. It's that simple."
The argument Butler makes is also personal. "If I hadn't found my way onto that clinical trial 15 years ago," she said, "I wouldn't be here talking to you today."
—Edward R. Winstead