A Prescription for Prevention?
Scientists are working to understand the molecular processes that transform normal cells into cancer cells in the hope they can prevent the disease before it starts.
By Marci A. Landsmann
When Therese Bevers was a physician in residency at the University of Texas Health Science Center at San Antonio in the 1980s, she would order standard blood panels for her patients. At the time, doctors would note high cholesterol as a risk factor for heart disease and counsel their patients to eat healthier and keep their weight down. But they could offer little else. Then, in 1987, the U.S. Food and Drug Administration (FDA) approved the first commercial statin, lovastatin. Since then, studies have shown that by lowering cholesterol, statins reduce the overall frequency of heart attacks by approximately 25 to 30 percent.
“Clearly the cardiology field is decades ahead [of oncology] in learning to impact risk factors and decrease overall risk development,” says Bevers, who has been the medical director of the Lyda Hill Cancer Prevention Center at the University of Texas M.D. Anderson Cancer Center in Houston since it opened in 1996.
Traditionally, cancer prevention has meant reducing risk through lifestyle choices such as healthy eating, using sunscreen or not smoking. But researchers and physicians like Bevers are working toward being able to recommend preventive treatments based on patients’ individual genetic profiles and other factors that may predispose them to cancer.
Prevention in Practice
In some cases, physicians are already able to prescribe personalized interventions for those at high risk of developing cancer. For example, physicians know that from 45 to 65 percent of women who inherit mutations in the BRCA1 or BRCA2 genes will go on to develop breast cancer by age 70. Between 11 and 17 percent of women with the BRCA2 mutation and 39 percent with the BRCA1 mutation will develop ovarian cancer by age 70. (By comparison, 12 percent of women in the general population will develop breast cancer in their lifetime, and 1.3 percent of women will develop ovarian cancer.)
Women with BRCA mutations, particularly if they are in their childbearing years, may decide to undergo increased screening to monitor their status and catch breast cancer as early as possible if it arises. Others undergo risk-reducing surgery to remove their breasts, fallopian tubes or ovaries. Since some tissue remains, surgery does not eliminate the chances of developing ovarian or breast cancer. But women who have one of these mutations and undergo a double mastectomy can reduce their risk of developing breast cancer by 95 percent. Removing both ovaries and fallopian tubes can reduce a woman’s risk of developing ovarian cancer by 90 percent.
“For those people [with these genetic mutations], the interventions might be a little more dramatic because the risks are more dramatic, but at least we can identify these patients now,” says oncologist Judy Garber, director of the Center for Cancer Genetics and Prevention at the Dana-Farber Cancer Institute in Boston. “That’s a great thing, but we still have a lot of work to do.”
Certain types of benign breast lesions, such as atypical hyperplasia and lobular carcinoma in situ, also increase a woman’s chances of developing breast cancer. Of these two types of breast disease, atypical hyperplasia is slightly more common, showing up in 10 percent of benign biopsies. Research indicates that approximately 30 percent of women diagnosed with atypical hyperplasia, characterized by abnormal growth in cells that contain some but not all the features of cancer, develop breast cancer in 25 years of follow-up. In other studies of women with this condition, taking selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, which work by blocking the estrogen in breast cells, reduced the risk of developing breast cancer by 41 to 79 percent.
Kathy Gahm of Houston is one of Bevers’ patients. She learned she had atypical hyperplasia in 2015 after a breast biopsy. Gahm, now 59, had two immediate family members with hormone-related cancers: Her sister had been diagnosed with stage III breast cancer in 2006 at age 57 and their mother, who tested negative for the BRCA1 and BRCA2 mutations, was diagnosed with stage IIIC ovarian cancer in 2005 at age 83. Gahm’s family history and benign breast disease diagnosis increased her risk of developing breast cancer. She agreed to take tamoxifen for five years to reduce her breast cancer risk.
“I wanted to make sure that I was taking proactive steps rather than reacting to a diagnosis in a few years,” says Gahm. “I want to drive the bus. I don’t want the bus driving me.”
Making Prevention More Precise
In an attempt to keep more patients in the driver’s seat, scientists are taking a closer look at high-risk patients to better understand how cancer develops and what treatments might help to prevent it. “We think of cancer as being a thing that appears once it is diagnosed. But in fact, it’s a process that leads to the development of what you find on the scan as cancer,” says medical oncologist Eva Szabo of the National Cancer Institute (NCI) Division of Cancer Prevention in Rockville, Maryland. “We’ve been really focusing on treating that cancer, but the 20 to 40 years before you have the identifiable invasive cancer, that’s the premalignancy. And that absolutely is, I think, one of the most important things to focus on in cancer prevention.”