Dr. Naseem Khorram, a nephrologist based in Los Angeles, experienced a life-altering moment during what should have been a joyous time in her life. While undergoing routine bloodwork for her second pregnancy to screen for chromosome abnormalities in the fetus, she received unexpected test results indicating potential health concerns for herself. Despite being healthy and having a progressing pregnancy, the results were “atypical for maternal chromosomal DNA variants,” leading to further investigations.
The possibility of malignancy was raised, prompting her obstetrician-gynecologist to recommend a full-body MRI for cancer screening. This revelation was a terrifying experience for Khorram, a 36-year-old mother of two, who faced the uncertainty of a potential cancer diagnosis. Although her insurance approved coverage for the MRI, the hospital where she sought care did not offer this service. Instead, she joined a study at the National Institutes of Health focusing on women with abnormal prenatal DNA-sequencing test results like hers.
The study led to a diagnosis of stage II Hodgkin lymphoma, a cancer of the lymphatic system, through a full-body MRI scan. Khorram’s journey through chemotherapy during her pregnancy ended successfully, with the completion of treatment just before the birth of her daughter. She emphasizes the importance of advocating for oneself and pursuing additional diagnostic work to potentially save lives in similar situations.
Gratefully, Khorram is now cancer-free and looking forward to a peaceful holiday season with her husband and two daughters. Reflecting on her older daughter’s support and her younger daughter’s joyful presence, she acknowledges the blessing of their health and resilience. As one of the participants in the NIH study exploring prenatal cell-free DNA sequencing for cancer detection in mothers, Khorram’s story serves as a reminder of the importance of proactive healthcare measures and the value of family in times of adversity.
A recent study published in the New England Journal of Medicine found that nearly half of participants with abnormal prenatal DNA-sequencing results were also diagnosed with cancer. Dr. Diana Bianchi, the senior author of the study, emphasized that this discovery is significant but does not mean all pregnant individuals should be alarmed. She explained that receiving such results does not equate to a 48% chance of having cancer but rather highlights the importance of further evaluation and taking the results seriously.
Prenatal genetic testing aims to identify fetal aneuploidy conditions like Down syndrome by analyzing cell-free DNA fragments from the placenta in the mother’s bloodstream. This screening, offered to all pregnant individuals, can also detect cancer as tumors release DNA fragments similar to the placenta. The study, conducted between December 2019 and 2023, revealed that some participants with abnormal sequencing results had undiagnosed cancers, including lymphoma, colorectal, and breast cancers.
The researchers used whole-body MRIs and standard tests to confirm cancer diagnoses in these participants. A specific chaotic pattern across multiple chromosomes was observed in sequencing results of individuals with cancer, suggesting a potentially higher cancer risk. Identifying this pattern on laboratory reports can prompt timely cancer screening for such individuals.
Overall, these findings underscore the importance of thorough evaluation and follow-up for individuals with abnormal prenatal DNA-sequencing results, recognizing the opportunity for early cancer detection and treatment.
Identifying an unusual test result can involve factors such as uterine fibroids or issues with the placenta. However, when physicians observe a cluster of abnormal test results with a disorganized sequencing pattern, it could indicate the need for further evaluation to explore potentially more serious underlying conditions, noted Bianchi. She emphasized the importance of timely action in such cases, as additional testing has been proven to save lives. On the other hand, delays in diagnostic workups post-delivery have led to cancer progression in some cases.
Dr. Britta Weigelt, a molecular geneticist at Memorial Sloan Kettering Cancer Center, highlighted the significance of the observed chaotic chromosomal abnormalities in the test results related to cancer, suggesting that this specific pattern could serve as a potential biomarker for maternal cancer detection in future studies.
Despite a lack of symptoms in a significant portion of participants with cancer, Bianchi stressed that these cases represent “hidden cancers” that may go unnoticed. She shared examples of individuals attributing symptoms to pregnancy-related issues rather than underlying cancer, underscoring the importance of treating pregnant individuals promptly and not delaying interventions based on their pregnancy status.
While the study’s findings show promise in the detection of maternal cancer through cell-free DNA sequencing, the researchers acknowledged the need for further research to explore its broader applications in identifying cancer cases in pregnant individuals. The hope is that if an atypical prenatal DNA-sequencing test result indicates a potential link to cancer, physicians could consider ordering additional imaging, such as an MRI, to further investigate.
Bianchi expressed optimism that demonstrating the effectiveness of MRI imaging in detecting cancer could lead to improved access to this diagnostic tool for pregnant individuals with abnormal DNA sequencing patterns. She emphasized the potential of these findings in guiding healthcare decisions and ultimately saving lives, especially considering the relatively rare occurrence of cancer during pregnancy in the US. Establishing guidelines for managing atypical prenatal DNA-sequencing results and determining the appropriate timing for additional testing could be beneficial in enhancing cancer detection in this population.
, Weigelt said. Although the new study suggests that abnormal findings on cfDNA require additional workup, that is not currently the standard of care, said Dr. Emeline Aviki, gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center – Long Island. And the study methodology “does not tell us whether or not early detection will translate to a difference in outcomes for all of the cancers that were identified, as this was not its intended purpose,” Aviki, who was not involved in the new study, wrote in an email. Cell-free DNA has the potential to identify cancer, but “the way in which we adopt these technologies remains important, as it can create significant anxiety and additional testing for 50 percent of women who, in fact, have no issue, while potentially benefits the others, who have an unknown cancer,” she said. “Future studies will need to test how to optimize use so that we can garner the most benefit and least harm from this very exciting technology.” It’s a timely discussion, as the incidence of cancer among adults under 50 has been increasing in the United States, said Dr. Sarah Kim, a gynecologic surgeon at Memorial Sloan Kettering Cancer Center who was not involved in the new study. Among adults 65 and older, adults 50 to 64 and those younger than 50, “people aged younger than 50 years were the only one of these three age groups to experience an increase in overall cancer incidence” from 1995 to 2020, according to a report released earlier this year by the American Cancer Society. As this trend emerges, the United States could see more cancer cases among the specific population of pregnant people. “More cancers are being diagnosed in younger patients,” Kim said. “In this special population of pregnant patients, because noninvasive prenatal testing has become mainstream, I think it does provide a unique opportunity to potentially diagnosis patients with cancer.” But she said that when it comes to tests like prenatal cell-free DNA sequencing, certain cancers may be more easily detected through the bloodstream than others. “Gynecologic cancers specifically have a lower amount of cell-free DNA that’s released into the bloodstream, just because of the way it spreads inside of a patient, as compared to, for instance, colon cancers or breast cancers that spread through the bloodstream,” Kim said. “While the technology is not quite there to be used as a screening tool for cancer, I think it’s something that’s important and needs to be developed,” she said. “Because the goal should be to catch cancers earlier, when they are treatable.”
