Breast cancer survivors may benefit from a yearly blood test to detect new cancers

Early detection is one of the most important ways to successfully combat cancer. Yet screening guidelines leave critical gaps, particularly for high-risk individuals. In the past 10 years, multicancer early detection (MCED) blood tests have been developed that screen for many cancers at once. These tests work by analyzing blood for cancer-associated proteins and patterns in circulating cell-free DNA. A new modeling study in JCO Precision Oncology led by Dr. Kemal Gogebakan in the lab of Dr. Ruth Etzioni at Fred Hutch asks an important question: would these tests be especially useful for breast cancer survivors, who face a higher-than-average risk of developing a different type of cancer later in life?

Surviving breast cancer is a tremendous achievement, but it doesn't put patients in the clear. Breast cancer in particular is notorious for “late recurrences”—secondary breast cancers that arise years or even decades after the original tumor has been treated. While breast cancer survivors are at highest risk for subsequent breast cancer, they have roughly a 17% higher chance of developing another cancer compared to age-matched women with no cancer history. This is partly due to shared genetic risk factors, treatment side effects, and natural fluctuations or treatment-related hormonal changes. Hormone receptor (HR)-negative breast cancers (those that don't express estrogen or progesterone receptors at high levels or depend on these hormones for growth and survival) carry an even higher subsequent cancer risk than HR-positive cancers.

“This is one of the first studies to quantify the potential benefit of multicancer screening in a high-risk population. Most modeling work in this field, including our own prior works, has focused on average-risk individuals. Breast cancer survivors represent an important high-risk group in which multicancer screening may have distinct clinical value,” Dr. Gogebakan highlights. “They face elevated risk of developing new primary cancers, yet current survivorship guidelines only recommend mammography for surveillance, with very limited guidance on screening for other subsequent malignancies. In the absence of standardized guidelines, survivors might be increasingly accessing blood-based multicancer early detection tests on their own initiative, without an evidence base to guide their decisions or their oncologists' recommendations.”

In place of running a clinical trial (which would take decades), the researchers used a mathematical model of how cancers develop, become detectable, and get diagnosed. They simulated hundreds of thousands of virtual women between the ages of 50-74 who were either breast cancer survivors (including those with both HR-positive and HR-negative tumors) or age-matched women with no cancer history. The authors used age-specific cancer incidence rates by HR status from the Surveillance, Epidemiology and End Results (SEER) program and assumed cancers could be detected by MCED 1-2 years before clinical diagnosis, based on patient data from published serum studies.

The model tracked 16 different cancer types including lung, colorectal, ovarian, pancreatic, and uterine, and simulated what would happen with and without annual MCED blood testing. The model accounted for survivor-specific elevated risks for each of the 16 cancer types individually (varying by HR status) and higher all-cause mortality among survivors. They varied two key parameters: how long a cancer is detectable before symptoms appear (the "sojourn time") and how sensitive the test was at catching early-stage tumors (either 30% for a conservative estimate or 50% for an optimistic estimate), producing six plausible scenarios to encompass real-world uncertainty.

Across every scenario, multicancer screening reduced the rate of late-stage cancer diagnoses and the benefit was consistently greater for breast cancer survivors than for average-risk women. In the most optimistic scenario, HR-negative survivors saw up to 111 late-stage diagnoses prevented per 100,000 person-years (a 26% relative reduction), compared to 84 per 100,000 among average-risk women (20% reduction).

The cancers driving the most benefit were consistent across all groups. Lung cancer alone accounted for 34-38% of the late-stage diagnoses prevented. Colorectal cancer contributed 14-16% to late-stage reduction. Ovarian cancer contributed about 10-11% of the benefit in HR-negative survivors, nearly double its contribution in HR-positive survivors and average-risk women, since HR-negative breast cancer is specifically associated with elevated ovarian cancer risk. “The ovarian cancer finding in HR-negative survivors was particularly striking; this elevation in HR-negative survivors is a genuinely new finding that underscores the importance of thinking about survivor subgroups separately,” Gogebakan adds.

Current survivorship guidelines for breast cancer focus almost entirely on watching for recurrence or a new breast tumor. This study argues that blood-based MCED tests could fill a critical gap by screening for the many other cancers survivors are at elevated risk of developing. The authors also note that a targeted approach—namely focusing specifically on lung, colorectal, and ovarian screening—might capture most of this benefit with even higher per-cancer sensitivity.

“The significant contribution of this work is that it affirms and estimates the extent to which the benefits of multicancer screening in breast cancer survivors may exceed those in the average-risk population. Not all breast cancer survivors are the same: HR-negative survivors have a higher risk of new primary cancers, and our projections show they stand to gain more from multicancer screening,” Gogebakan says. “We hope our study can inform future survivorship guidelines. It is important for survivors to be aware of their excess cancer risk even many years after their initial diagnosis, and equally important to be able to offer them interventions to mitigate that risk.”

The authors also plan to extend their adaptable framework to other high-risk survivor populations such as childhood cancer and colorectal cancer survivors.

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Ruth Etzioni and Kathleen Malone contributed to this research.

The spotlighted research was funded by the Rosalie and Harold Rea Brown Endowed Chair and the National Cancer Institute.

Gogebakan KC, Lange J, Gulati R, Dubard-Gault ME, Drescher CW, Malone KE, Etzioni R. 2026. Impact of Multicancer Screening on Late-Stage Cancer at Diagnosis in Breast Cancer Survivors: A Modeling Study. JCO Precis Oncol. doi: 10.1200/PO-26-00305.