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

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Sung Gwe Ahn, MD, PhD, discusses survival outcomes with ovarian function suppression-based endocrine therapy based on the HERA trial in HR-positive, HER2-positive breast cancer.

Sung Gwe Ahn, MD, PhD

Sung Gwe Ahn, MD, PhD

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

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