OncoExTra and OncoDetect Identify Actionable Biomarkers and ctDNA Status in Breast and Colorectal Cancers

Molecular profiling using whole exome and whole transcriptome testing identified at least 1 actionable alteration in 98.0% of patients with breast cancer and colorectal cancer (CRC), and circulating tumor DNA (ctDNA) monitoring identified ctDNA-positive disease at least once in 61.7% of patients, according to findings from a poster presented at the 2026 AACR Annual Meeting.¹

Among 196 evaluable patients, 54.6% (n = 107) possessed biomarkers associated with an on-label FDA-approved matched therapy. Of patients with hormone receptor (HR)–positive, HER2-negative breast cancer, 58.8% with stage I to II disease (n = 17) and 54.8% with stage III to IV disease (n = 31) had on-label alterations. Among patients with CRC, these rates were 75.0% and 70.3%, respectively. Notably, ctDNA positivity rates varied by disease subtype across both cohorts, reaching as high as 83.3% in patients with triple-negative breast cancer (TNBC) and 84.6% in those with rectal cancer.

“OncoExTra testing in this breast cancer and CRC cohort detected actionable alterations regardless of ctDNA status with potential for matched therapies,” lead study author Gargi D. Basu, PhD, and coauthors wrote in the poster.

Basu is the senior principal medical development director at Abbott Cancer Diagnostics, previously Exact Sciences, in Phoenix, Arizona.

What was the rationale for evaluating actionable alterations and ctDNA status among patients with breast and colorectal cancers?

The incidence of breast cancer continues to rise, with over 300,000 new cases diagnosed annually in the United States (US). Additionally, CRC remains the second leading cause of cancer-related death in the US. Tumor molecular profiling is increasingly used to reveal distinct biological behaviors and identify actionable alterations that inform therapy selection. Furthermore, the detection of ctDNA provides a non-invasive method to monitor the effects of surgery and therapy, as well as to assess the risk of disease recurrence.

Notably, in April 2025, OncoDetect became available for use in the detection of minimal residual disease in the form of ctDNA variants in patients with solid tumors.² This assay can detect ctDNA at levels as low as 1 molecule per every 20,000 circulating free DNA molecules.

Through the present study, the investigators aimed to describe the frequency of these alterations and their relationship to ctDNA status across different stages and subtypes of breast cancer and CRC.¹

What was the design of this analysis of actionable alterations and ctDNA levels in breast and colorectal cancers?

This study evaluated 196 patients—88 with breast cancer and 108 with CRC—who underwent whole exome and whole transcriptome profiling using the OncoExTra test either before or after the assessment of ctDNA status using the OncoDetect test.

Actionable alterations were defined as those with existing on-label or off-label FDA-approved therapies, as well as those associated with active clinical trials. Patients were considered to have ctDNA-positive disease if they had a positive finding at any time point during the study. In total, 41.8% of patients in the total population had ctDNA assessed at more than 1 time point.

What were the baseline characteristics of the patients included in the testing analysis for breast cancer and CRC?

The overall population had a mean age of 63.1 years (standard deviation, 13.9), and 67.9% of patients were female. At the time of the first ctDNA test, the clinical stages of the patients were as follows:

• Stage I: 6.1%
• Stage II: 23.0%
• Stage III: 40.8%
• Stage IV: 23.0%

Within the breast cancer cohort, disease subtypes included HR-positive/HER2-negative (n = 53), HER2-positive (n = 6), triple-negative (n = 18), and not otherwise specified (n = 11). The CRC cohort was composed of patients with colon cancer (n = 95) and rectal cancer (n = 13).

What were the key biomarker and ctDNA findings from this analysis of OncoExTra and OncoDetect in breast and colorectal cancers?

In patients with HR-positive/HER2-negative breast cancer, PIK3CA mutations were more prevalent in those with ctDNA-negative disease (53%) compared with those who had ctDNA-positive disease (32%). For patients with CRC, KRAS gain-of-function alterations were observed across ctDNA-positive and -negative subsets; these patients may be eligible for targeted therapies, according to the authors.

Across clinical stages, specific on-label biomarkers included:

• Breast cancer: PIK3CA mutations (detected in 52.9% of patients with stage I to II disease vs 32.3% of those with stage III to IV disease), ESR1 mutations (5.9% vs 6.5%), and PTEN alterations (5.9% vs 6.5%)
• CRC: KRAS mutations (detected in 50.0% of patients with stage I to II disease vs 55.4% of those with stage III to IV disease), BRAF V600E mutations (7.1% vs 6.8%), and tumor mutational burdenof at least 10 mut/mb (21.4% vs 8.1%)

Additionally, the analysis revealed that 20% of patients with stage II and 23.6% of those with stage III CRC harbored PI3K pathway alterations (including PIK3CA mutations, PIK3R1 mutations, and PTEN inactivation), indicating these patients may benefit from treatment with aspirin. Rare but potentially actionable findings, such as 1 RET fusion, were also identified within the CRC cohort.

References

1. Basu GD, Johnson N, Deem A, et al. Investigating the value of testing for actionable alterations and circulating tumor DNA in breast and colorectal cancers. Cancer Res. 2026;86(supple 7):3243-3243. doi:10.1158/1538-7445.AM2026-3243
2. Exact Sciences launches the OncoDetect molecular residual disease test. News release. Exact Sciences. April 22, 2025. Accessed April 20, 2026. https://www.exactsciences.com/news-events/press-releases/exact-sciences-launches-the-oncodetect-molecular-residual-disease-test