Addition of OFS to Endocrine Therapy Improves Survival in HR+, HER2+ Early Breast Cancer

The addition of ovarian function suppression (OFS) to adjuvant endocrine therapy with or without trastuzumab (Herceptin) improved long-term survival outcomes in patients with hormone receptor–positive, HER2-positive breast cancer, according to data from an exploratory analysis from the phase 3 HERA trial (NCT00045032).

The exploratory analysis, which was presented at the 2024 ESMO Congress, aimed to address the benefits of OFS in premenopausal patients (n = 965) with hormone receptor–positive, HER2-positive breast cancer. Primary end points were disease-free survival (DFS) and overall survival (OS). Patients were randomly assigned to tamoxifen alone (n = 501) or OFS-based endocrine therapy (n = 464).

Findings showed that at a median follow-up of 11.0 years, patients from the OFS plus endocrine therapy arm experienced a 10-year DFS rate of 70.9% vs 59.6% for those in the tamoxifen arm (HR, 0.68; 95% CI, 0.53-0.88). The OS rate at 10 years was 74.0% in the tamoxifen arm and 84.7% in the OFS arm (HR, 0.64; 95% CI, 0.46-0.89).

During the exploratory analysis, DFS and OS were also compared in the OFS arm based on the form of endocrine therapy patients received: OFS plus tamoxifen or OFS plus an aromatase inhibitor (AI). Patients in the OFS/AI group achieved superior survival outcomes vs patients from the OFS/tamoxifen group. At 10 years, the DFS rate was 65.2% in the OFS/tamoxifen group and 78.7% in the OFS/AI group (HR, 0.54; 95% CI, 0.38-0.75). The OS rate at 10 years was 79.7% in the OFS/tamoxifen group and 91.3% in the OFS/AI group (HR, 0.48; 95% CI, 0.30-0.77).

Furthermore, in the OFS cohort, the 10-year DFS rates were improved for those given OFS/tamoxifen alone (73.5%) and OFS/tamoxifen plus trastuzumab (81.3%) compared with those given OFS/AI alone (64.2%) and OFS/AI plus trastuzumab (65.6%). The 10-year OS rates for OFS/tamoxifen alone, OFS/tamoxifen plus trastuzumab, OFS/AI alone, and OFS/AI plus trastuzumab were 89.3%, 92.1%, 80.2%, and 79.5%, respectively.

In an interview with OncLive®, lead study author Sung Gwe Ahn, MD, PhD, discussed the findings from the exploratory analysis, next steps for research, and the clinical implications of these findings.

Ahn is a professor in the Department of Surgery at the Gangnam Severance Hospital at Yonsei University College of Medicine in South Korea.

OncLive: What was the rationale for this exploratory analysis of the HERA trial?

Ahn: [For patients with] hormone receptor–positive, HER2-positive breast cancer, [the analysis] compared outcomes between different oral endocrine agents.

What were some of the key findings from this analysis?

The most important key finding is that in young [patients with] hormone receptor–positive, HER2-positive breast cancer, they need OFS in conjunction with endocrine therapy, especially if the patient has high-stage [disease] and some high-risk features; in that case, the patient needs OFS as a part of endocrine therapy.

Are there any next steps that are planned for this research?

These data are very limited, so we need some observational studies. We are considering constructing a prospective cohort including these patients. We want to look deep into the real-world data in these patients.

What are the clinical implications of the findings from this study?

If a patient has high-risk [disease], a high stage, or residual tumor burden after targeted therapy, and if the patient is young with hormone receptor–positive, HER2-positive breast cancer, you can consider the addition of OFS to endocrine therapy.

Reference

Moon S, Bae SJ, Kook Y, et al. Ovarian function suppression in HR-positive, HER2-positive breast cancer: An exploratory analysis from the HERA trial. Ann Oncol. 2024;35(suppl 2):S310. doi:10.1016/annonc/annonc1577