Cancer diagnosis used to be a simple, binary call: either someone had the disease or they didn’t. And patients with the same broad class of cancer tend to receive the same class of therapy. It was a one-size-fits-all approach to cancer care, and for many patients that size wasn’t a good fit at all.
“We used to treat just based on whether the tumor was bigger than a centimeter,” says Kimberly Allison, a surgical pathologist and breast cancer researcher at Stanford University School of Medicine. “The biology didn’t matter; you pretty much gave chemotherapy to everybody.”
The good news is that this has changed dramatically in the last few decades. Patients are no longer categorized, assessed and treated based only on the location and size of their cancer. Clinicians and researchers now look for DNA mutations and a range of other biological indicators. With this information, clinical teams can approach each case with more nuance, diagnosing and treating patients according to their personal physiology—and the specific characteristics of their cancer.
“Healthcare providers can personalize treatment plans, tailoring therapies that are a better match for the patient’s tumor biology,” says Roula Qaqish, US franchise head of women’s cancers at AstraZeneca. “This means targeting the cancer’s weaknesses, while potentially reducing side effects.”
This has been achieved in large part through two complementary but distinct types of tests: genetic screening and biomarker testing. As researchers continue to home in on the underlying genetic factors of different cancers, the role of these tests in both diagnosis and treatment is only going to grow.
Precision testing
The first of the two testing methods, genetic testing, helps to assess the cancer risk of healthy people and their family members. The technique sifts through a person’s inherited DNA for gene variants known to increase the risk of developing cancer, or affect how the tumor might respond to treatment.
People with a hereditary mutation in either the BRCA1 or BRCA2 gene, for instance, have a far higher risk of developing breast, ovarian, prostate and pancreatic cancer. “The average woman in the US has about a 13 percent chance of developing breast cancer,” Qaqish says. “For women with a BRCA mutation, their risk of developing breast cancer in their lifetime rises to 70 percent.” That’s why around half of women in the US who test positive for a BRCA mutation, including the actress and filmmaker Angelina Jolie, choose to have a mastectomy as a precaution.
The second testing method, biomarker testing, tends to happen once someone has already been diagnosed with cancer. Biomarkers are objective, quantifiable signs that can help clinicians understand how a disease is progressing, or how it might respond to specific treatments. In the case of cancer, these could be genetic mutations, or tell-tale proteins, or even tiny fragments of DNA shed by tumors into the bloodstream. These can reveal mutations acquired over the patient’s lifetime that explain what turned healthy cells cancerous and how best to target them. Common non-inherited alterations in breast cancer include alterations in genes such as PIK3CA, AKT1 and PTEN.
“When alterations like these are identified, patients may be eligible for targeted therapies specifically designed to attack those mutations,” Qaqish says.
Test, then treat
Biomarker testing can reveal whether a patient’s cancer is HR-positive —whether it has receptors for the hormones estrogen or progesterone—and whether it expresses high levels of the protein HER2. Together this information reveals a patient’s likely prognosis, which helps doctors choose the type of chemotherapy. “You're going to treat more aggressively a triple-negative breast cancer that doesn't have those biomarkers of estrogen or progesterone receptors, or HER2,” Allison says. “For HR-positive cancers, generally we want to treat less.”
Biomarker testing can also be used to monitor treatment effectiveness over time, which can reveal whether a therapy is still working or if adjustments are needed. And some cancer treatments only work for people whose cancers have certain biomarkers. These include some advanced immunotherapies that stimulate the immune system to seek and destroy tumors.
Allison, who underwent treatment for breast cancer herself in 2008, has seen firsthand the benefits of biomarker testing for patients. Checking whether cancer cells carry receptors for the hormones estrogen and progesterone, along with the protein HER2, can indicate how aggressive the cancer is. “Those biomarkers really divide breast cancers into treatment pathways.”
“While new biomarkers are being discovered every year, that knowledge isn’t evenly distributed across cancer types,” says Omar Perez, head of medical diagnostics for US medical affairs at AstraZeneca. “If you look at non-small cell lung cancer, for example, there are at least 10 guideline-recommended biomarkers that should be tested for,” Perez says. “Breast cancer, as well, has both risk biomarkers and predictive biomarkers. In other indications, such as pancreatic cancer, the number of biomarkers identified is much lower.”
Spreading the word
While personalized treatment is now an option in many cancer types, data suggests there’s a long road ahead to make genetic and biomarker testing widely available. A report published in 2023 found that among more than a million patients with cancer in the states of California and Georgia, fewer than 7 percent underwent germline genetic testing—an analysis of inherited genes—within two years of diagnosis to guide genetically targeted treatment and inform potentially high-risk family members. Another study of more than 1,000 US oncology practices found that less than half of non-small cell lung cancer patients were tested for five key biomarkers between 2018 and 2020, although the data showed that testing rates were rising.
“Increased awareness and education can help more people get appropriate care,” says Perez, adding that awareness of testing varies widely among patients, providers and payers.
AstraZeneca works with both patients and physicians to help spread the word about testing options, whether it’s generating evidence to inform medical testing guidelines or partnering with patient advocacy organizations on awareness efforts for the patients and caregivers they support.
“We also aim to ensure multidisciplinary care teams receive the latest updates on biomarker testing and guidelines,” Perez says. “It’s a holistic approach.”
Knowing about biomarkers and their potential to shape targeted treatment strategies could help more patients make an informed decision about testing. “Many factors go into this decision,” Perez says. “But knowledge is power, and I do believe that every patient should have that choice.”
Discover how AstraZeneca is helping to empower cancer patients with biomarker testing. Learn why comprehensive biomarker testing is critical for cancer diagnosis and treatment from the No One Missed campaign, driven by the LUNGevity Foundation and Living Beyond Breast Cancer.
