Christine Ambrosone lost a husband to Hodgkin’s lymphoma in 1996, so she understands the frustrations people harbor toward the fits and starts in cancer treatment advances.
She also understands cancer is tough, conniving and irrational.
“The more we learn, the more complex we realize cancer is,” said Ambrosone, senior vice president for population sciences and chairwoman of the Department of Cancer Prevention and Control at Roswell Park Comprehensive Cancer Center.
Ambrosone grew up in North Buffalo. She was a single mom waiting tables in the Theater District in the late 1980s, having just received her bachelor’s in medical anthropology from the University at Buffalo, when Dr. Edwin Mirand, then dean of students at Roswell and one of her regular dining customers, suggested she enroll in the cancer center's epidemiological doctoral program.
She met her second husband while she pursued her Ph.D. He died the year after she graduated. She left Buffalo to work with the Division of Molecular Epidemiology at the National Center for Toxicological Research in Jefferson, Ark., then, in 2000, joined the faculty at Mount Sinai as director of epidemiology in the Derald H. Ruttenberg Cancer Center. She returned to Roswell in 2002. She and her husband Warren Davis live in East Aurora.
Ambrosone works with a team of 20 researchers at Roswell who focus on finding ways to keep cancer at bay – both for those who have never had it and those who have been diagnosed.
One of her secret weapons is the Data Bank and BioRepository, a collection of thousands of questionnaires answered by Roswell Park patients during the last generation. She and others continue to analyze the repository in various ways to determine what traits and behaviors are shared by those who have lived longest after learning they had cancer.
During the last decade, she and others at Roswell also have collaborated with cancer researchers across the globe to make their findings more robust.
"Instead of one hospital enrolling 50 or 100 patients over a year, the cooperative groups can enroll thousands," she said.
Q: My chiropractor describes cancer as a flawed, veracious parasite that ends up killing itself as it kills its host. What is cancer and why is it so challenging to treat?
Our cells are damaged constantly by all sorts of different things but there are so many checks and balances. The cell cycle will stop to check for DNA damage. DNA damage can be repaired. If the cell is already pretty badly damaged, it'll get sent to a cell death. There are all these opportunities. The body really protects.
Once there is a cell that has mutations that can overcome these checks and balances, there are two major drivers. Oncogenes are kind of like the gas pedal that tells the cell, "Grow, grow, grow, grow." Then there are tumor suppressor genes that pretty much are like the brakes that say, "Stop, that's enough." If you get a cut, the cells need to grow a scab but then the wound-healing process needs to stop.
What generally drives cancer is if you get mutations in the tumor suppressor genes or the oncogenes and they can't really do their jobs. The growth is either always on or the tumor suppressor is off, and the cells grow. With cells growing, that's usually not what will kills people. It's when cells from that tumor break off, get into the blood or lymphatic system and go to another organ and set up house.
Your chiropractor is kind of right. The cancer cells want to keep their host alive but eventually, if you die, then the cancer cells go, too.
What makes cancers so hard to treat is that they're all so different. With lung cancer, we know there are different cell types, different kinds of lung cancer, but they'll have different types of mutations. Treatment now is trying to target those specific mutations because not all cancers will respond to the same drugs. That's why they'll do three different drugs to treat a cancer, trying to get them to three different pathways.
Q: What is a molecular epidemiologist?
Epidemiology comes from the word epidemic, which means "upon people." An epidemiologist is studying the determinants and distributions of disease. A really cool example was John Snow, the father of epidemiology. There was an outbreak of cholera in London in 1854 and they thought it was from the air. He thought, "What do all these people have in common?" He went around and asked people where they got their water from, and all the people who had cholera got their water from the same pump. The goal of epidemiology is prevention, so he removed the pump handle so people couldn't drink that water. That's applicable to what we do in cancer and any other type of disease. We look at who has the condition or disease, and what they have in common, to try to identify causes. It's like smoking and lung cancer.
Molecular epidemiology is now taking that much deeper. For smoking and lung cancer, why doesn't everybody who smokes get cancer? Why only some people? We get down on the molecular level and try to look at differences in DNA sequences that we're born with that may make us more susceptible to carcinogens and tobacco smoke, or any other factors.
Q: What are the most important things you and other researchers have learned about cancer during the last generation?
That cancer is not one disease. Even within breast cancer – and this is a major area of research – there are many different kinds. This concept is really important for treatments because different types of breast cancer get treated with different drug regimens. It's also important for studying etiology and risks. In our research, we and others always thought that having children reduced a woman's risk of having breast cancer, but that's only true for estrogen receptor (ER) positive breast cancer that's less aggressive and more common in older white women. With ER negative, which is more common in younger women and African-American women, having children actually increases risk, so you've got the same factor working differently in these types of breast cancer.
Q: What are the most important things you and other researchers hope to learn in the next decade?
In our group, we really want to prevent cancer. A lot of the efforts here at Roswell involve tobacco research because tobacco causes so many different types of cancer. In the work of our tobacco researchers, many people think that electronic cigarettes may be better, but we don't know what that's going to do to kids, so that's a really, really important area; always will be for cancer.
Q: What do you expect might take longer to understand?
I don't study all cancers but I would have thought more would be understood about pancreatic cancer. It's almost never diagnosed until a late stage, and people don't generally live very long once they're diagnosed with it. Even with pancreatic cancer, they're learning more, but it's incremental. People need to understand. There may occasionally be a big breakthrough but mostly it's learning more about what's going on within the tumors and the cells, and it takes us to the next step. It builds the common knowledge that we have.
Q: Can you talk about key things you’ve learned about the influence of genetics and the environment (behavior) on cancer?
The key environmental factor related to cancer etiology is tobacco smoke and carcinogens from other sources. For different cancers, there's different exposure. For colon cancer, eating meat – especially well-done meat – we know now that increases risk. We know now that hormones are related to breast cancer. Hormone replacement therapy was kind of a big find. Once researchers realized that was increasing risk for breast cancer, people stopped taking it and the rates of breast cancer dropped pretty quickly.
Risk factors for different cancers are different. It's been really hard to pinpoint but it really does look like that for most cancers, a diet high in fruits, vegetables and whole grains is going to reduce risk – a but it's hard to nail down studies of diet. You'd have to follow someone from birth and really record what they're eating because our exposure is all through life. When you're diagnosed with cancer at 60, it may be things you were exposed to in utero or during your teens or in early adulthood, so it makes it tricky to pinpoint environmental factors.
Genetically, there are people born with things like the BRCA mutations, these highly penetrant mutations that are very rare. But if people carry that genetic variance, they're at higher risk for certain cancers. Then there are genetic variants that are really common, where 20 to 60 percent of the population will have them. That, in combination with the environment may increase risk. If you smoke, and you carry a genotype for DNA repair, then you're at higher risk. This is an area that I've been working on since I started in epidemiology. We're learning more and more but not as much as we would like.
Q: How important is it to attack cancer from both the genetic and environmental side?
This is a relatively young field. In the last 10, 15 years there have been more and more studies. Once someone is diagnosed with cancer, they want to know if there's something they can do, something they can change in their life or their behavior. There wasn't a lot of information, and now there are more and more studies suggesting that physical activity improves survival outcomes. Some studies suggest that higher levels of vitamin D help. It's the only vitamin that I take – I'm a firm believer in eating a really good, balanced diet – but up here in Buffalo we don't get very much sun for our vitamin D. We have a collaboration of colleagues in California. We've got a cohort of more than 4,000 women from the time they're diagnosed with breast cancer, looking at their diet, their physical activity, other behaviors when they're diagnosed and through treatment, and looking at how that may affect their outcomes. We really want to be able to tell people what may help them not just improve survival but to reduce side effects from cancer treatment and improve their quality of life.
Q: One of the things that strikes me having handled the Refresh section for the last five years is that the same things that help people with any number of chronic conditions seem to be among the basic things helping people either prevent cancer or live a longer life after a cancer diagnosis.
Right. The data is so strong for physical activity and not smoking. The recent Roswell Park Data Bank and BioRepository study is really important because, even if you didn't start exercising until after diagnosis, it still will improve outcomes. More research needs to be done to dig deeply, and see if there are other factors that could be affecting this relationship, but there's so many studies now – especially work in breast cancer – that show exercise improves outcomes and reduces risk of cancer, too.
Q: With what you know now, what can you say to people about steps they can, and should, take to prevent cancer, and the important steps they can take after diagnosis?
To prevent cancer, don't smoke. Exercise and maintain a healthy body weight. Maintain a balanced diet. Have a lot of colors on your plate with fruits and vegetables. Eat whole grains, small amounts of meat.
The same things apply if you're diagnosed with cancer – and we haven't talked about alcohol. Alcohol increases risks of several types of cancer. There are several studies showing that it's associated with poor prognosis, as well. I think moderation is the key here when we talk about drinking and diet and exercise. You don't have to be a real road warrior. Any exercise a few times 20 minutes a week will help.