How your genes can help your doctor fine-tune your diagnosis — and treatment.
Cancer is, to some extent, a numbers game. Numbers represent your odds of surviving, and of the cancer returning once you’ve been treated. Over the past three decades, the numbers for breast cancer have moved in the right direction. Death rates dropped by 36 percent from their peak in the late 1980s. Today, a woman diagnosed with an early-stage breast cancer has five-year survival odds of nearly 100 percent. This improved outlook is due, in large part, to advances like personalized medicine, which have helped doctors detect cancer more accurately and fine-tune treatment for each patient.
Personalized medicine looks for certain changes to genes — the string of code that directs how your body looks and operates. These changes, or mutations, can help your doctor determine your odds of getting cancer, choose a treatment that will yield the best results with the fewest side effects, and predict the likelihood of your cancer returning after treatment.
While the personalized medicine approach might sound high-tech, it’s not brand new. “The field of breast cancer has been using personalized medicine for decades,” says Carey Anders, MD, associate professor of medicine at UNC Chapel Hill, and member of the UNC Lineberger Comprehensive Cancer Center. One avenue of personalized medicine — gene tests to identify women at high risk for breast cancer — has been around for more than 20 years.
Breast cancer susceptibility genes
Since the 1990s, doctors have been able to test for mutations to two genes — BRCA1 and BRCA2. Changes to these genes compromise the body’s ability to repair damaged DNA, thus fostering tumor formation. Having one or more of these genes increases your risk for breast cancer by sevenfold or more.
Learning that you have one of these genes can help simplify very difficult treatment decisions. “If we have an early-stage cancer with the BRCA1 or BRCA2 genes, we counsel patients to consider preventive mastectomy and ovary removal,” Anders says. “It also helps patients understand that if they have daughters or sisters, they should consider genetic screening.” Many other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, and CDH1, are under investigation.
Biomarkers — indicators of molecular processes related to disease — play a pivotal role in breast cancer management. “Breast cancer is not one disease. It’s multiple diseases,” Anders says. For the past few decades, one way doctors have delineated these individual diseases is to detect whether a breast cancer has receptors that enable it to respond to the hormones estrogen or progesterone.
Estrogen and progesterone receptors are proteins on the surface of cells that have the ability to attach to either of these hormones. Estrogen receptor-positive cancers have estrogen receptors on their surface and grow in response to estrogen. Progesterone receptor-positive tumors have progesterone receptors and grow when exposed to progesterone. Collectively, these hormone receptor-positive tumors account for up to 75 percent of breast cancers.
Another 20 percent of breast cancers stem from a gene mutation that leads to the overproduction of a protein called HER2, which promotes tumor growth. Cancers that don’t fall into either of these categories because they lack estrogen and progesterone receptors, as well as HER-2, are called triple-negative.
Each of these categories of tumor behaves in a different way, and responds in a unique way to treatment. Therefore, knowing which of these tumor markers a woman has can help her doctor predict which treatment will have the best benefit/risk profile. For example, instead of using a one-size-fits all treatment like radiation or chemotherapy on HER2-positive breast cancers, doctors use targeted drugs like trastuzumab (Herceptin) and pertuzumab (Perjeta), which have been shown to work more effectively with fewer side effects on this very aggressive tumor type. “With the addition of Herceptin, the risk of HER2-positive cancer recurring is dramatically lower,” Anders says.
Other therapies target the molecular processes inside a cell that help tumors take root and spread. The tyrosine kinase inhibitor lapatanib (Tykerb) blocks enzymes that help cancer cells grow. It’s approved for women with HER2-positive breast cancers. PARP inhibitors repair damaged DNA, and could be promising targets for BRCA cancers, which stem from an inability to fix this damage.
Gene expression profiling
In women with certain hormone receptor-positive cancers, doctors can take personalization one step further with gene expression profiling. Tests like Oncotype DX and PAM50 (Prisogna) look for changes to genes that can predict how the cancer is likely to behave, and whether a particular treatment will work on it. Gene expression profiling is still relatively new. Some doctors are starting to offer the technology, but others defer patients to clinical trials where gene profiling is being studied.
Next-generation sequencing is the “brave new world” in personalized medicine for breast cancer, according to Anders. “This is where we’re starting to see differences in the molecular makeup of breast tumors.”
Harnessing the power of genomic exploration that began with the Human Genome Project, next-generation sequencing techniques quickly and accurately scan huge volumes of genetic material to identify specific mutations and biomarkers that can guide treatment. “Many clinical trials are in progress, and I’m hopeful in the next several years, as the results become known, we’ll be able to decide on treatment algorithms beyond ER, PR, and HER2,” she says. “I think the advent of next-generation sequencing will really help direct our patients to make more informed decisions.”
If you’ve been diagnosed with breast cancer and are interested in learning more about personalized medicine, Anders suggests looking into a research study. “I encourage patients to learn more about clinical trials that are available to them based on their tumor characteristics,” she says. You can ask your doctor to recommend a study, or visit clinicaltrials.gov.
March 31, 2020
Christopher Nystuen, MD, MBA