The Role of Ki-67 and ctDNA as Prognostic or Predictive Markers in Breast Cancer
Sara M. Tolaney, MD, MPH, discusses the evolving role of Ki-67 and circulating tumor DNA as prognostic or predictive biomarkers in breast cancer.
This is a synopsis of an OncView series featuring Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute.
Sara M. Tolaney, MD, MPH, Chief of Breast Oncology at Dana-Farber Cancer Institute, discussed the use of Ki-67, a proliferation biomarker sometimes measured in early-stage estrogen receptor (ER)-positive breast cancer. High Ki-67 levels (>20%) were initially linked to greater risk reduction from the CDK4/6 inhibitor abemaciclib in the monarchE trial, forming the basis of abemaciclib's initial FDA approval in high Ki-67 patients. However, benefits were subsequently demonstrated across Ki-67 levels, leading to an expanded label.
Dr. Tolaney noted reproducibility challenges with intermediate Ki-67 values from 5-30%. Very high (>30%) or very low (<5%) values are more reliable. Given pathological issues, her institution does not routinely report Ki-67, instead relying on genomic assays like the Oncotype DX test to gauge chemotherapy benefit and recurrence risk.
Some European groups use short-term estrogen suppression to evaluate Ki-67 changes and guide chemo decisions, stopping chemotherapy if Ki-67 falls to <5% on endocrine therapy. However, additional validation is needed.
Circulating tumor DNA (ctDNA) analysis is also emerging to detect minimal residual disease (MRD), especially in early-stage breast cancer after standard treatment. Detectable ctDNA signals high recurrence risk. However, current assays lack sensitivity, with ctDNA-negative patients still relapsing. Better assays and clinical trials are needed to determine if MRD detection can guide intervention to improve outcomes.
In metastatic disease, Dr. Tolaney finds ctDNA analysis valuable for genomic profiling after disease progression, guiding targeted therapy switches. Turnaround times allow practical use of results.
Key trials and areas of active research include improving ctDNA sensitivity for MRD detection in early breast cancer and developing efficacious MRD-triggered interventions to prevent relapse after definitive therapy.
In summary, Ki-67 and ctDNA analyses show promise for personalizing breast cancer treatment, but currently have limitations in early-stage disease. More validation and clinical data are needed to support their routine use for prognosis, prediction, and guiding therapeutic de-escalation or intensification. Practical applications today include ctDNA for genomic alterations guiding therapy switches in metastatic disease after progression on standard treatments.
*Video synopsis is AI-generated and reviewed by Cancer Network editorial staff.
