Imagine facing a breast cancer diagnosis and being told you need aggressive treatments that could change your life forever—yet what if those weren't necessary for you? That's the heart-wrenching dilemma many women with early-stage breast cancer confront today. But here's where it gets exciting: groundbreaking research suggests we could use cancer cells floating in patients' blood to customize treatments, potentially avoiding overtreatment. Let's dive into how this innovative approach might transform care, making it more personalized and precise.
Globally, about 2.3 million women are living with breast cancer right now, and roughly a quarter of them are diagnosed at an early stage known as ductal carcinoma in situ, or DCIS for short. Think of DCIS as cancer that's confined to the milk ducts of the breast and hasn't invaded surrounding tissues yet. Patients with DCIS often have a positive outlook, but without intervention, it can turn invasive in anywhere from 10% to 53% of cases—numbers that highlight the uncertainty and high stakes involved.
Given these risks and the lack of reliable ways to predict outcomes for individual patients, doctors have traditionally advised everyone with DCIS to undergo treatment. This might include a lumpectomy (removing just the tumor and some surrounding tissue) or even a mastectomy (surgery to remove the entire breast). If a woman opts for a lumpectomy, radiation therapy is usually recommended to target any remaining cancer cells. Additionally, for those whose DCIS tests positive for hormone receptors, anti-hormonal therapy—medications that block hormones fueling the cancer—can be part of the plan.
'As early detection through tools like mammograms can be life-saving, we're now advising screenings at younger ages, forcing more young women into tough, life-altering decisions,' notes Sunitha Nagrath, a professor of chemical engineering at the University of Michigan and co-corresponding author of a study published in Science Advances. 'But right now, patients are often choosing treatments without clear data on which option might work best for their unique situation and risk profile.'
This one-size-fits-all approach can lead to overtreatment for some, where women endure invasive procedures their cancer might not have needed, while others might not get enough intensity, allowing the disease to return. Studies indicate that about 10% of cases recur within 10 years after surgery alone—a statistic that underscores the need for better tools to assess individual risks.
Enter the goal of researchers like Fariba Behbod, a professor of pathology and laboratory medicine at the University of Kansas Medical Center and another co-corresponding author: 'We're aiming to pinpoint biomarkers—specific indicators in the body that signal disease changes—that can differentiate patients who truly need aggressive steps like surgery, radiation, and hormone therapy from those who might only require surgery or could even skip treatment altogether.'
And this is the part most people miss: these biomarkers could be hiding in plain sight, in the patient's blood. Tumors sometimes release cancer cells that circulate undetected by standard lab methods, potentially seeding new growths elsewhere. To capture them, Nagrath developed a 'labyrinth chip' back in 2017 alongside Max Wicha, an oncology professor at the University of Michigan Medical School. This clever device works like a microscopic maze: by flowing a blood sample through its winding channels, it separates out larger cells—like cancer and white blood cells—from smaller ones, collecting enough for analysis from just a few milliliters of blood. Picture it as a smart filter that isolates the key players in the bloodstream, making advanced testing possible.
In their recent study, the team applied this chip to blood samples from 34 DCIS patients at the University of Kansas Medical Center. They examined the active genes in these circulating cancer cells and compared them to cells from tissue biopsies taken from the same individuals. The tissue-based cancer cells fell into four distinct subtypes based on gene activity, with two of these showing up prominently in the blood. These subtypes displayed genes linked to progression (like spreading to other areas), resistance to chemotherapy, and even platelet binding—a clever trick some cancers use to dodge the immune system, as if hiding in plain sight from the body's defenders. Other active genes might help these cells evade immune detection entirely, allowing them to persist undetected.
'This insight lets us zero in on what might signal that these cells are circulating and potentially dangerous,' explains Neha Nagpal, a University of Michigan doctoral student in chemical engineering and the study's lead author.
But here's where it gets controversial: the study uncovered racial differences that could stir debate. The six Black participants had higher levels of circulating cancer cells and more signs of immune suppression compared to white participants, mirroring the unfortunate reality of higher breast cancer mortality rates among Black women. Since race isn't biologically determined, these patterns likely stem from environmental factors like exposure to pollutants, socioeconomic stresses, or disparities in healthcare access. Is this a wake-up call for addressing systemic inequalities in cancer care, or does it risk overgeneralizing and stigmatizing certain groups? What are your thoughts on how we should tackle these disparities?
Looking ahead, Nagpal adds, 'We intend to figure out which cell types and markers can actually reach and colonize distant sites in the body.' To gather this data, they're transplanting patient-derived cancer cells into mice, monitoring blood levels and gene activity after four months, and tracking disease progression in both the animals and human participants. While this animal testing could spark ethical debates—after all, is it justifiable to use mice for human benefit?—it aims to refine our understanding without direct human risks.
The study received support from esteemed institutions like the University of Michigan's Forbes Institute for Cancer Discovery, the Kansas University Cancer Center, the Kansas Institute for Precision Medicine, and funding from the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards Program. The labyrinth chip itself was crafted in the Lurie Nanofabrication Facility, backed by federal grants, and RNA sequencing happened at the University of Michigan's Advanced Genomics Core. Notably, a UM startup called Bloodscan Biotech, aided by Innovation Partnerships, has licensed the chip technology, with Nagrath and the University holding financial stakes—raising questions about potential conflicts of interest in medical innovation.
Nagrath also serves as a professor of biomedical engineering, co-director of the Liquid Biopsy Shared Resources at UM’s Rogel Cancer Center, and a member of the UM Biointerfaces Institute.
Source: University of Michigan
In wrapping up, this research opens doors to more tailored breast cancer care, but it also invites tough questions: Should we rethink aggressive treatments for all DCIS cases, or is caution still warranted? How do you feel about using blood tests to guide decisions—could this reduce overtreatment, or might it create new anxieties? And on the topic of racial disparities, what steps do you believe we need to take to ensure equitable access to such advancements? Share your opinions in the comments below; I'd love to hear your perspective!
