# Efficacy of neoadjuvant endocrine therapy with CDK4/6 inhibitors in locally advanced breast cancer

## TL;DR

This study shows that neoadjuvant endocrine therapy with CDK4/6 inhibitors is as effective as chemotherapy for certain breast cancer patients.

## Contribution

The study introduces neoadjuvant endocrine therapy with CDK4/6 inhibitors as a viable alternative for HR-positive breast cancer patients unresponsive to chemotherapy.

## Key findings

- Endocrine therapy with CDK4/6 inhibitors had comparable objective response rates to chemotherapy.
- Patients on endocrine therapy showed better pathological responses and Ki67 reduction.
- Sequential endocrine therapy improved outcomes in chemotherapy-insensitive tumors.

## Abstract

Neoadjuvant treatment for hormone receptor (HR)-positive breast cancer remains limited, particularly for tumors that are insensitive to neoadjuvant chemotherapy. This study aims to compare the efficacy of neoadjuvant endocrine therapy combined with CDK4/6 inhibitors to that of traditional neoadjuvant chemotherapy.

A total of 49 patients receiving neoadjuvant endocrine therapy plus CDK4/6 inhibitors and 210 receiving neoadjuvant chemotherapy were enrolled. Magnetic resonance imaging was performed to assess tumor responses every 2-3 cycles of treatment. Propensity score matching (PSM) was performed to balance baseline characteristics.

Both before and after PSM, the objective response rate (ORR) in the endocrine therapy group was comparable to that of the traditional chemotherapy group. After matching, the ORR was 64.6% (95% CI, 49.5-77.8) in the endocrine group and 56.3% (95% CI, 41.2-70.5) in the chemotherapy group (P = .532). A higher proportion of patients in the endocrine group achieved a pathological complete or near-complete response (Miller-Payne grades 4-5, 13.5% vs 10.4%) and post-treatment Ki67 < 5%, indicating a potential long-term benefit. Patients with ≥30% regression in maximal tumor diameter after 2 cycles of chemotherapy were considered chemotherapy sensitive. Among patients with tumors less sensitive to chemotherapy, sequential treatment with neoadjuvant endocrine therapy plus CDK4/6 inhibitors significantly improved ORR (61.8% vs 32.4%, P = .028) and was associated with greater Ki67 reduction and improved Miller-Payne grades.

Neoadjuvant endocrine therapy is a promising alternative for HR-positive breast cancer, especially for patients with poor responses to chemotherapy.