Davidson is senior vice president and director of the Clinical Research Division at Fred Hutch and president and executive director of its clinical-care partner, Seattle Cancer Care Alliance. Last week at the annual meeting of the American Association for Cancer Research in Atlanta, Davidson shared how researchers are working toward lowering the occurrence rates and overall number of deaths caused by these cancers. To do this, they're developing new strategies to prevent and detect these malignancies early, when they’re most treatable, in women who are most at risk. They're also working to develop individualized therapy tailored to each patient.
“Our goal is to think about how we are going to close the gaps for those common cancers,” Davidson said. “So, all of these things together — precision prevention, risk-stratified screening strategies and targeted therapies — should help us reduce the burden of cancer in women around the globe.”
Cancer prevention and screening — with precision
To work toward reducing the number of deaths caused by these cancers, health care providers first need to focus on cancer prevention and screening strategies, Davidson said. There are many steps women can take to reduce their chances of getting these cancers.
“For lung cancer, of course that is very simple. Avoid tobacco,” she said. For breast cancer, evidence shows that certain drugs that affect cancer cells’ use of the hormone estrogen (called estrogen-receptor modulators and aromatase inhibitors) lower the likelihood that a person at high risk of breast cancer will develop it.
For colorectal cancer, research has shown that lifestyle and environmental factors such as reducing alcohol consumption, not smoking and maintaining a healthy diet play an important role in preventing this disease.
While prevention efforts reduce someone’s risk of getting cancer, it’s not possible to prevent every case. The next best thing is to detect the cancer as early as possible, when it’s easier to treat successfully.
To detect early lung cancers in people at high risk, doctors use low-dose CT scans, a newer form of imaging that takes very detailed X-rays that can potentially pick up early stages of lung cancer that might not been seen with a traditional CT scan. Mammography and MRIs are used to screen for breast cancer. Some of the tests used to detect colorectal cancers and precancers are colonoscopies and fecal immunochemical testing for blood in the stool.
“These are pretty general recommendations, so one of the things we’d love to do would be to begin to think about how we can move from general guidelines toward an effort that is more precision prevention and screening,” Davidson said.
Davidson cited research led by Fred Hutch colleague Dr. Ulrike "Riki" Peters through the Genetics and Epidemiology of Colorectal Cancer Consortium. GECCO Consortium researchers are pooling large data sets from over 40,000 participants to refine risk prediction models for colorectal cancer. They’ve derived a score that takes into account 19 different lifestyle and environmental factors together with 64 common genetic variants to identity more than 18,000 people in their data set who might be at high risk for colon cancer.
“By using this, we might be able to help individuals understand that if they have a high risk score, they ought to be starting their screening very early, well under the age of 50, whereas other individuals who have a very low-risk score might be in a position where they would not have to start routine screening until much later in life,” Davidson said. “This obviously would be a major advantage as we try to think about how to target these things.”
Targeted therapies for women with cancer
It is important to understand that breast, lung and colorectal cancer are not single diseases, Davidson said. “Each of them has a variety of molecular subtypes, and understanding those subtypes can help us think about the best way of using targeted types of therapies,” she said.
For lung cancer patients, some of these targeted therapies include drugs that stop tumors from growing new blood vessels to feed their growth (angiogenesis inhibitors) and drugs that enhance the immune system’s cancer-fighting powers (checkpoint inhibitors).
For patients with colorectal cancer, certain molecular features can make their tumors vulnerable to particular drugs. For example, people with HER2-positive tumors may be able to use anti-HER2 therapy, and for those with mutations in a gene called BRAF, treatment with BRAF, MEK, or epidermal growth factor receptor, or EGFR, inhibitors might be beneficial.
Davidson, a recipient of Fred Hutch’s Endowed Chair for Breast Cancer Research, specializes in the study of breast cancer biology and treatment. Through her role as a member and chair of the Breast Committee for the Eastern Cooperative Oncology Group (a large cancer-research network), she is working with other investigators to develop new therapies.
Breast cancer clinicians have long used prognostic and predictive factors to guide the choice of treatment in partnership with their patients. Prognostic factors help to gauge the natural history of newly diagnosed breast cancers, and predictive factors help to forecast a tumor’s response to targeted therapies. Researchers are now moving from tests that look at a handful of genes to using multigene predictive and prognostic tests, which allow researchers to look at multiple genes at once.
Clinicians and researchers are looking at using these tests to estimate a patient’s prognosis at the time of diagnosis with early breast cancer, to predict response to chemotherapy in some early breast cancers that are hormone-receptor positive, and to gauge whether extended adjuvant hormone therapy is a treatment option for women with estrogen receptor– or progesterone receptor–positive breast cancer.
“It’s an exciting time,” Davidson said. The next step for tests to guide treatment for breast and other cancers will be to move from using relatively small panels of markers to more sophisticated, next-generation sequencing, she said.
Cancer disparities in women
However, according to Davidson, to think about ways to dramatically lower death and occurrence rates of these cancers, we need to understand that a woman’s likelihood of developing a cancer, and of dying from it, are different in different areas around the globe.
When you map these data, the differences pop out. For example, in this map created by the International Agency for Research on Cancer, it’s clear that women across Russia, China, and parts of Latin America and Africa are more likely to die of their cancers; however, when you click “incidence” as an indicator, you can see that women are much more likely to ever develop cancer at all in the United States, Canada and Australia.
“Looking at these maps gives us an opportunity to think about what the possibilities are to improve outcomes,” Davidson said. “There is lots of work that can be done across the world as we think about this incidence and mortality burden of cancers of all types.”