A biomarker is a measurable substance in the body that indicates a biological state or condition. Ovarian cancer often grows silently in its early stages, presenting a diagnostic challenge. For this reason, biomarkers are an important part of managing the disease, providing insights that influence diagnosis, treatment, and long-term monitoring. These molecular clues, found in blood or tissue, offer a window into the cancer’s behavior.
Commonly Used Ovarian Cancer Biomarkers
The most established biomarker for ovarian cancer is Cancer Antigen 125 (CA-125), a protein used for over three decades. CA-125 is found on the surface of many ovarian cancer cells and can be detected in the bloodstream. Its levels are elevated in approximately 90% of women with advanced epithelial ovarian cancer, the most common type.
A more recently adopted biomarker is Human Epididymis Protein 4 (HE4). HE4 is a protein produced by ovarian cancer cells and measured with a blood test. Studies have shown that HE4 is often less likely than CA-125 to be elevated due to benign gynecological conditions, such as endometriosis. This greater specificity makes it a valuable complementary tool.
To refine risk assessment, clinicians use the Risk of Ovarian Malignancy Algorithm (ROMA). This is a statistical calculation that combines the blood levels of CA-125 and HE4 with a patient’s menopausal status to produce a numerical score. This score estimates the probability that a pelvic mass is malignant, helping to distinguish between benign and cancerous growths before a biopsy.
Distinct from protein biomarkers are genetic markers, which indicate a hereditary predisposition to the disease. Mutations in the BRCA1 and BRCA2 genes are the most well-known genetic risk factors. These inherited mutations significantly increase a woman’s lifetime risk of developing ovarian cancer. Identifying these mutations through genetic testing is important for assessing risk and can also guide treatment decisions, as some therapies are specifically effective against cancers with these genetic changes.
Clinical Applications of Biomarkers
One of the primary uses of ovarian cancer biomarkers is to assess whether a pelvic mass, often discovered through an ultrasound, is cancerous. For a woman with a pelvic mass, a physician will order CA-125 and HE4 tests. The results are then used in the ROMA calculation to stratify risk. A high ROMA score suggests a greater likelihood of malignancy, which would prompt a referral to a gynecologic oncologist for specialized surgical care.
Biomarkers are also used to monitor how well a patient is responding to treatment. Before starting therapy, such as chemotherapy, a baseline level of CA-125 is established. The CA-125 level is then measured periodically throughout the treatment. A significant decrease in the CA-125 level indicates that the treatment is successfully shrinking the tumor, while a stable or rising level may suggest the cancer is not responding.
After a patient has completed initial treatment and is in remission, biomarkers play a role in surveillance for recurrence. Regular monitoring of CA-125 levels is a standard part of follow-up care. A rising CA-125 level can be the first sign that the cancer has returned, often appearing before physical symptoms or evidence on imaging scans. This early detection allows doctors to initiate treatment for the recurrence sooner.
Limitations and Interpretation
A significant challenge with biomarkers like CA-125 is their lack of specificity, which can lead to false positives. Elevated CA-125 levels are not exclusive to ovarian cancer. They can be caused by a variety of benign conditions, including endometriosis, uterine fibroids, pelvic inflammatory disease, and even pregnancy or menstruation. A high reading in a woman without a diagnosed pelvic mass can cause anxiety and may lead to unnecessary diagnostic procedures.
The sensitivity of these biomarkers is also a concern, as they can produce false negatives. Not all ovarian cancers secrete CA-125 or HE4, particularly in the disease’s earliest stages. A woman can have a normal biomarker level while still having ovarian cancer. This limitation means that a normal test result cannot definitively rule out the disease.
These issues of specificity and sensitivity are why current biomarkers are not recommended for screening the general population. For a screening test to be effective, it must be highly accurate to avoid causing more harm than good. The high rate of false positives from CA-125 testing in asymptomatic women would lead to a large number of unnecessary surgeries for a small number of cancers detected.
Emerging Research in Biomarker Discovery
To overcome the limitations of single markers, researchers are investigating multi-marker panels. The concept is that combining a larger set of different biomarkers into a single test can improve diagnostic accuracy. By analyzing a panel of proteins or other molecules simultaneously, these tests aim to create a more distinct and reliable signature for early-stage ovarian cancer, reducing the rates of false positives and negatives.
A promising area of research is the development of liquid biopsies that detect circulating tumor DNA (ctDNA). As tumors grow, they shed small fragments of their genetic material into the bloodstream. Advanced technologies can now detect and analyze this ctDNA from a blood draw. This approach holds potential for detecting ovarian cancer earlier than current methods and for monitoring treatment response with greater precision.
Beyond proteins and DNA, scientists are exploring other molecular indicators through fields known as “omics.” Proteomics involves the large-scale study of proteins, while metabolomics focuses on metabolites, the small molecules involved in cellular metabolism. By examining the complex patterns of these molecules in the blood, researchers hope to identify novel biomarkers that can signal the presence of early-stage ovarian cancer with much higher accuracy.