Ki-67 Index: A Powerful Prognostic, But Not Predictive, Marker in Post-NAC Adjuvant Therapy

New data presented at the European Society for Medical Oncology (ESMO) 2025 Congress, drawn from the monarchE trial, shed significant light on the evaluation of the Ki-67 proliferation marker in breast cancer patients who receive neoadjuvant chemotherapy (NAC).¹ The analysis specifically examined the prognostic and predictive value of the Ki-67 index, both before and after NAC, and how changes in the index affect subsequent adjuvant treatment outcomes.¹

The Ki-67 test assesses how quickly cancer cells are dividing, as the Ki-67 protein is present during all active phases of mitosis.² A higher level of Ki-67 indicates that cancer cells are multiplying at a faster rate, generally suggesting a more aggressive tumor with a potentially worse prognosis. Although Ki-67 is used globally in breast cancer diagnosis, its overall benefit and application in treatment guidance remain controversial.² For the purposes of this high-risk population of hormone receptor-positive (HR+), HER2-negative, node-positive patients in the monarchE study, Ki-67 was assessed as high (>20%) or low (<20%).¹

Ki-67: A Strong Prognostic Indicator

The analysis confirmed that the Ki-67 index remains a critical prognostic factor for patient outcomes, regardless of the timing of the assessment. Patients with a high Ki-67 index, both pre- and post-NAC, demonstrated a higher risk of recurrence.¹

In the patient cohort that received NAC (36.5% of the total study population), the data showed that NAC was highly effective in reducing proliferative activity. Approximately 75% of tumors that started with a high Ki-67 index saw that the index reduced to low following NAC.¹

However, the analysis highlighted a group at exceptionally high risk: those whose tumors retained a high Ki-67 index following NAC. This subgroup, when treated with endocrine therapy (ET) alone, had a remarkably low 4-year invasive disease-free survival (IDFS) rate of just 43.5%. In contrast, patients whose tumors shifted from high Ki-67 pre-NAC to low Ki-67 post-NAC demonstrated a robust 4-year IDFS rate of 74.7% in the ET-alone arm, underscoring the strong prognostic value of this change.¹

No Predictive Value for Abemaciclib

Although Ki-67 was strongly prognostic for recurrence risk, the study concluded that the index was not predictive of abemaciclib (Verzenio; Lilly) treatment benefit. Abemaciclib plus ET, which had already shown sustained IDFS improvement over ET alone in this high-risk population, demonstrated consistent treatment benefit across all subgroups defined by Ki-67 status or changes.¹

Regardless of whether the tumor was high or low Ki-67 pre-NAC, high or low post-NAC, or if the index shifted (eg high to low or remaining high), the addition of abemaciclib to ET provided a benefit. For instance, in the highest-risk group (retained high Ki-67), abemaciclib plus ET increased the 4-year IDFS rate to 57.5% from 43.5%. In the most favorable group (high to low Ki-67 shift), abemaciclib plus ET achieved a 4-year IDFS rate of 92.8% compared to 74.7% with ET alone.¹

The data shared at the 2025 ESMO Congress confirm the Ki-67 index and its response to NAC are valuable tools for identifying patients with the highest risk of recurrence. However, the consistent benefit of abemaciclib across all proliferative subgroups suggests that clinicians should not Ki-67 status to determine eligibility for abemaciclib treatment in this setting. This finding reinforces the utility of Ki-67 as a prognostic crystal ball for recurrence risk, but not as a treatment decision gatekeeper for abemaciclib.

REFERENCES

1. Martin M, Johnston SR, Harbeck N, et al. MonarchE: evaluation of prognostic and predictive value of Ki-67 index pre and post neoadjuvant chemotherapy (NAC) and changes following NAC. Presented at: ESMO 2025. October 19, 2025. Berlin, Germany.

2. Nolan-Pleckham M. The Ki-67 proliferation marker test and breast cancer treatment. VerywellHealth. Updated October 9, 2025. Accessed December 10, 2025. https://www.verywellhealth.com/ki-67-tumor-marker-test-430609#:~:text=Key%20Takeaways,2