BCRF sat down with Dr. Richard R. Love to discuss his current work and interest in breast cancer research. Read on to learn more.
Q: Tell us about yourself as a scientist and how you became interested in global breast cancer research.
A: We're all a product of our pasts. When I was a teenager, my family moved around internationally as my father's career grew. Because of this experience, I saw parts of the world that most do not. The poverty in places like India deeply moved me from the age of 15, when I visited Calcutta. As a college student, I returned to the US. This was the 1960s, during the war in Vietnam. Being a student during that war left strong conflicts in me. I continued on to medical school and cancer medicine. Years later, in 1991, The International Union Against Cancer, an organization that I had joined and worked with for more than a decade, became interested in initiating a project in Vietnam. I joined this effort. It was in some ways an opportunity to get the monkey off my back in terms of my considerably mixed feelings about the war, and try to do something positive.
At first in Vietnam it seemed that the challenges were educational, working with local doctors, nurses and cancer patients alike. But soon I came to the realization that we also needed to develop clinical research. With increased awareness of the disease comes the need for treatments that are affordable and effective. My first affiliation with an international cancer clinical trial was in Vietnam. That's what got me on the way to being involved in global clinical research.
Q: Did you ever consider another kind of career than that of the medical science?
A: No. I love what I do at all kinds of levels. It's difficult, but also very rewarding. For example, I spend about 20 percent of my time in Bangladesh. When I'm there, at least once a day, I find myself thinking, "Oh, dear, they didn't teach me how to do this in school." I'm confronted with the reality that in order to achieve results, namely, helping women with breast cancer in a population-dense but largely poor place, I've got to be more eclectic in my thinking and problem-solving. I can't fall in to what William Easterly described in his book "White man's burden," or overlooking real possibilities for improvement because of excessive and often unhelpful planning.
In Bangladesh and other developing countries, the chronic disease transition is becoming more of a problem. With improved water, immunizations and nutrition, people are living longer. They reach the age when increasing malignancies occur. There's also more obesity, diabetes and heart disease, which complicates if not contributes to breast cancers. With Mohammad Yunus, the Bangledeshi Nobel Peace Prize laureate, I've been developing a population-based approach to breast cancer. The program involves educational, service and research projects in partnership with a non-governmental agency in a rural area called Khulna, where 7 million women live. Yunus' methods create sustainable social businesses, and we are working with him as part of the larger effort to create better health care systems in the country. I think we can be a good model for developing standards and practices that can go country-wide. If we can figure out how to do this in Bangladesh, with such population density and other challenges, then I think we can apply that knowledge in other, similar populations. I've learned that there are all kinds of ways of making things worse. I'm focused on making things better.
Q: You've mentioned your efforts in Bangladesh, Vietnam. You also have projects in The Philippines, China, Indonesia, Malaysia. Why so much focus on Asia?
A: Because that's where the greatest burden of breast cancer cases is. The number of new cases of breast cancer that occur globally per year is now estimated at 1.5 million. Over half of this total, or 800,000 cases, occurs in women in Asia, mostly in poor women.
Q: You are a public advocate as well as a clinician-researcher who describes global breast cancer research and clinical trials as a "win-win." What do you mean by this?
A: The prevalence of breast cancer in Asia is an opportunity to do some good in those countries and to understand breast cancer in ways we can't in the United States. The genetics of Asian women are different than those of Caucasian women and women of other ethnicities. That and factors like poverty, how it affects a women's health through her nutritional status, for example, reveal how known treatments work in different ways. There are many Asian women living in the United States and they also get breast cancer. We can bring new insights to their treatment here through the analysis of genetics in the Asian women we treat and study globally. In the United States, it costs approximately $5000 per patient to conduct a clinical trial. Our studies in Bangladesh, The Philippines and Vietnam cost about 18 percent of what I would need to run a study here. That even includes the lab technicians and researchers we employ here in Indiana and Ohio who handle our hundreds of flash frozen tumor samples for analysis!
Q: You have studied hormonal therapies-especially tamoxifen-in global populations. What have you learned?
A: Tamoxifen is the most widely used hormonal therapy in breast cancer. But it must be metabolized in certain way in order to be effective. In the body, this drug becomes endoxifen and that is what provides the therapeutic effect. There is increasing data that suggest that small differences in a gene called CYP2D6 determine whether a woman can metabolize tamoxifen properly. In Western populations of women of Europe and North America, we think that about six percent of women do not metabolize tamoxifen because of this genetic difference. We've been studying these genetic differences in Asian women for several years. We see CYP2D6 polymorphisms (different forms of the gene), responsible for the reduced metabolizing capacity, in 40-50 percent of women there. That's very significant and suggests that tamoxifen may be ineffective in that percentage of our Asian patients. Our studies in Vietnam and in the Philippines are now looking at blood levels of endoxifen for every single patient. This level of endoxifen in the blood after giving tamoxifen seems to be the real issue of importance.
Q: Another hypothesis you are testing in an international study is the timing of oophorectomy, or surgical removal of ovaries, as a treatment for metastatic, hormone-receptor positive breast cancer. What is the status of this investigation?
A: Breast cancer has been a neglected disease in many of the countries where I work. That is starting to change, but the reality is that the breast cancers we see in Asia are more advanced, and often metastatic. We're always trying to figure out practical, low cost, non-toxic and easily replicable treatments. They're the best kind of "public health oncology," and offer poor women in poor countries a better chance of surviving. Based on a lot of initial data, we've now got two studies running in seven Asian and two African countries. We think we can extend survival by about a year for advanced, metastatic breast cancer if we time the removal of ovaries to the second half of the menstrual cycle.
We've already seen very positive remissions of locally advanced disease in the patients involved in our study. The likely reason for this is because levels of progesterone drop off at this late stage of the menstrual cycle. Progesterone is thought to control certain proteins that are angiogenic. Cancers rely on these proteins to build a blood supply and fuel tumor growth. When progesterone is high, cancers do better. Removing ovaries at a time when progesterone has dropped off may create a more difficult environment for a hormone receptor positive breast cancer. This is the first time there's been a major pre-menopausal study in this subgroup of patients. We'll have our goal of 350 women in the study in 2011 or 12. If this timing issue is a real factor that will improve outcomes, these women with little hope will certainly benefit. And we can take this kind of knowledge back to our own context in the United States and put it to very good use as well.
Q: How close do you think we are to preventing or finding a cure for breast cancer?
A: It's an exciting time. Targeted therapy is not only about the tumor. The data on host biology is going to prove equally important. We're learning more and more about in whom breast cancer occurs, which will guide us to select better controls. If we're right in our hypothesis about the optimal time to remove ovaries, it helps us understand better how signaling control works in breast cancer. We can begin putting that kind of information in a bottle, in a way that's important to non-hormone receptor positive breast cancers, too. By thinking about more than the tumor in the conventional sense, we are going to develop some clever and simple ways of dealing with cancer.
Q: How has BCRF been helpful to you?
A: It has given me the freedom to focus on the kinds of questions that will truly personalize the nature of existing treatments, and within short periods of time. For example, you'd like to give a woman the drug that works best and that is associated with the minimum of side effects for her breast cancer. Yet here in the United States, it is hard to determine those who will and those who won't do well on a certain drug with a specific cancer. Why? Because once we know it works, we start using a new drug in every woman who might be helped by it. It then takes decades of prospective studies to figure out who isn't helped by it. I'll be retired by the time we have those results.
Look at tamoxifen in Asia. It's just coming into widespread availability and use. We can test a woman's endoxifen levels in Asia because there's overwhelming genetic evidence that it is a useful thing to check. We can ethically decide not to use tamoxifen if endoxifen levels are not high enough. If we're right about it correlating to a woman's response rate, then we'll have proof that taking a blood sample that measures a woman's endoxifen levels would improve decisions about treatment. In the Philippines, we'll know the answer to this question within three years.
Q: What are the biggest challenges in cancer research today?
A: Not letting cancer, a significantly complex illness, stand in the way of simple solutions that we can bring to bear on the situation and improve outcomes. I've seen what other global health practitioners have done with improving outcomes with communicable diseases, like diarrheal disease among children. They work with local populations to circulate valuable information and creatively apply solutions. Watching others make progress with seemingly impossible problems encourage me. Cancers are significantly complicated, but we can do better.
Q: What advice would you give to young researchers?
A: Think creatively in terms of the whole world. You'll be surprised at what it returns to you where you live. I just took a young Canadian researcher to Bangladesh, and introduced her to a genetic study there. Now, I receive an average of five or six e-mails a day from her about next steps on this project. She's absolutely taken by this study. She recognizes opportunities to answer questions in Bangladesh that she can't answer in Canada, or that we can't answer in North America in general. Five or ten years ago people didn't think about global cancer research as much. Was it arrogance? I think it was more a lack of realization of what tremendous opportunities are out there. We're realizing that particularly through partnerships with people, we can move the whole breast cancer agenda forward. Our new Administration is calling it "medical diplomacy," but the reality is that the whole world has to be part of the solution, whether it is ending wars or ending cancer.
Read more about Dr. Love's current research project funded by BCRF.