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Improving Endometrial Cancer Outcomes


March 30, 2010 – Endometrial cancer, also called uterine cancer, is the most common form of gynecologic cancer in the United States, with 40,000 cases diagnosed each year. While many women survive the disease, about 7,000 do die each year, and that number is growing. In this edition of Breakthroughs in Cancer Research, geneticist Paul Goodfellow, PhD, talks about advances in endometrial cancer diagnosis and treatment, including exciting discoveries for women with an inherited form of the disease. He also discusses a Specialized Programs of Research Excellence (SPORE) grant from the National Cancer Institute that was recently awarded to the Siteman Cancer Center. The grant includes researchers from across the country who are working to reduce the burden of endometrial cancer for women. 

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On this edition of Breakthroughs in Cancer Research, we'll discuss research aimed at improving the outcome for patients with endometrial cancer, a common cancer of women.

Host: I'm talking with Dr. Paul Goodfellow, a geneticist and expert on the genetics of endometrial cancer. Dr. Goodfellow is a member of the Siteman Cancer Center's senior leadership team, and along with Dr. David Mutch, he is leading a newly funded program at the Siteman Cancer Center to study endometrial cancer and its treatment. Dr. Goodfellow, thank you for talking with us today.

Goodfellow: It's a pleasure to be here.

Host: Tell us about endometrial cancer: What is it, and how many women are affected by it?

Goodfellow: Well, endometrial cancer is a cancer of the uterine lining, and it's actually the most common gynecologic malignancy in the U.S. Every year there are about 40,000 new cases diagnosed. And of those 40,000 women, approximately 7,000 will die. Dr. Mutch and I often think of this as the stepchild of gynecologic malignancies: the most common of the diseases, not talked about so much because overall survival's reasonable, certainly understudied and underfunded.

Endometrial cancer is actually a growing problem in the U.S. Not only is the incidence increasing, but we've made essentially no progress in reducing mortality from this disease. In fact, this year there'll probably be nearly twice as many women dying of endometrial cancer as cervical cancer.

Now we've made progress in treating some of the common forms of endometrial cancer. But I think what's happened over the past few decades is that there are more and more of the aggressive types of this cancer appearing. And it's those sorts that we don't have any good therapies for.

Host: What have we learned so far from basic studies about how the cancer develops?

Goodfellow: Well, perhaps one of the best understood parts of endometrial cancer biology is the role that estrogens, normal female hormones, play in the development of this disease. And many endometrial cancers (the most common form) are the result of excess of estrogen. In the early days of hormone-replacement therapy, women were given high doses – or abnormal doses – of estrogen, and that led to an increase in incidence of endometrial cancer. So we know that natural hormones can drive the development of this disease.

We've also learned that there are genetic factors that can contribute to risk for endometrial cancer. And I'm proud to say that here at the Siteman Cancer Center, we've made really important contributions to understanding how inherited genetic factors contribute to risk. About one in 40 women with endometrial cancer develop their disease because they were born with a genetic mutation. Our work and the work of our colleagues at Ohio State, the Mayo (Clinic) and at other institutions has really changed how we manage endometrial cancer patients. Those women with genetic disease are now brought into more intensive surveillance for uterine, ovarian and other cancers, along with their family members. And that's translated into reduced disease burden for the family as a whole.

Host: How is endometrial cancer treated, and what is the future for endometrial cancer treatment?

Goodfellow: This is a disorder in which surgical treatment is the primary therapy. Right now we struggle with figuring out which patients would benefit most from adjuvant therapies: chemotherapy or radiation therapy or new designer drugs —biologic therapies. The current approach to surgical management of these patients is changing. And it's going to be possibly even harder to know which woman needs chemotherapy and more importantly which woman can be spared the morbidity that's associated with chemotherapy. So studying the tumor DNA, other protein markers and also clinical features is really helping shape how we approach the management of these patients. We're going to get better at it to improve outcomes and to reduce the overall burden of disease — health care dollars and the actual personal burden to women who suffer surgeries and then chemo and other therapies.

Host: Let's talk about the recent SPORE grant in endometrial cancer that you were awarded. First, what does SPORE mean?

Goodfellow: The SPORE acronym stands for Specialized Programs of Research Excellence. And this is a National Institutes of Health, specifically National Cancer Institute, initiative to fund really good research in disease focus areas. And these grants are intended to advance science and take science to patient care. Every project on the grant includes both a clinician scientist and a laboratory scientist.

So over the past decade, the SPORE funding mechanism from the National Cancer Institute has really been recognized as the Good Housekeeping Seal of Approval for excellence in cancer research. They're focused on important problems and are awarded to the very best cancer research investigators and institutions. It's particularly important to our team that we have obtained the first SPORE at the Siteman Cancer Center. We believe that we're going to make really important contributions here and nationally in terms of the research and care in the field of endometrial carcinoma.

Host: So what are the goals of the research funded by the new grant?

Goodfellow: The overarching goal is to improve patient outcomes. And our projects – there are four of them – really span all aspects of cancer research, from the development of new approaches to prevent the cancer to new treatments and to determining better ways of finding out which patient needs what treatment.

One of the most exciting areas right now in our SPORE is the continued evaluation of a new way to treat endometrial cancers. And this is what's referred to as a biologic or targeted therapy. In 2007, our collaborative group, that's the Washington University/Siteman group and additional investigators, discovered mutations in a specific gene in endometrial cancers. And very quickly we were able to determine that we could take that genetic information and treat patients and tumor cells with drugs that specifically reversed that genetic problem.

A few weeks ago, we completed the first phase of a clinical trial that's being run through the cooperative group the Gynecologic Oncology Group that's testing our anti-FGFR2 gene drug. So this is a really exciting advancement for us, and it's really just the first phase. And we believe that we've laid the groundwork for even smarter trials to figure out which patients will benefit from which drugs.

One of the important research questions we're going to try to address through our SPORE mechanism is how best to disseminate information about genetic testing and gene-based surveillance and intervention in the general population. In the past few years, it's become obvious that we can do genetic tests and find out which endometrial cancer patients develop their disease because of an inherited genetic factor and we can take that information to their brothers and sisters and children and suggest that they might have different cancer surveillance. The real challenge in terms of research and education now is how to best use those tests in the general community so that every endometrial cancer patient benefits from it and how to help physicians apply this new knowledge in a way that's going to make a difference.

One of the things I think the Siteman Cancer Center should be most proud of is that they have been able to help put together what's probably the best endometrial cancer research team that can be assembled in 2010. This SPORE grant includes investigators from Ohio State University, the University of Buffalo, the Gynecologic Oncology Group, the Queensland University of Technology in Brisbane, Australia, UT Southwestern and more. And Siteman has catalyzed these interactions to ensure we are doing the best science.

Host: What message would you like women hearing this who have endometrial cancer or people who know women with endometrial cancer to take away? What kind of message do you want them to hear?

Goodfellow: Well, for anybody who knows me, I'm an optimist. And I think the most important message is that endometrial cancer is a disease that most women beat. The funding from the National Cancer Institute and the money that is coming from Siteman Cancer Center to ensure the success of this research is going to make a difference for all women with endometrial cancer. We're focusing our energies now on better treatments, but we're not ignoring prevention. So the message is that there are committed people who are doing their best to reduce the cancer burden on all fronts.

Host: For more information about endometrial cancer and its treatment, you can visit the Web site of the National Cancer Institute at