February 19, 2026

Abstract PD4-09: Impact of Duration of Adjuvant Endocrine Therapy on Clinical Outcomes in BRCA pathogenic variant Carriers with HR+/HER2- Early Breast Cancer

Q: What does this research mean for the field?

Extended adjuvant endocrine therapy (>5 years) significantly improves invasive disease-free survival and distant relapse-free interval in BRCA pathogenic variant carriers with HR+/HER2- early breast cancer compared to standard-duration therapy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

Key Points

To assess the impact of extended adjuvant endocrine therapy on clinical outcomes in BRCA pathogenic variant carriers with HR+/HER2- early breast cancer.
Cohort study derived from genetic counseling data at a cancer institute.
Included patients with HR+/HER2- early breast cancer who received adjuvant endocrine therapy.
Patient outcomes analyzed using Cox proportional-hazard models and landmark analysis.
Extended adjuvant therapy improved invasive disease-free survival (iDFS) by 69% compared to standard therapy (adjusted HR 0.31).
Distant relapse-free interval (DRFI) improved by 71% with extended therapy (adjusted HR 0.29).
BRCA variant status linked to a 50% higher risk of reduced iDFS (adjusted HR 1.5).

Abstract

Abstract Background There is limited evidence on the effect of extended adjuvant endocrine therapy (ET) in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer (EBC) carrying germline BRCA1 and/or BRCA2 (gBRCA) pathogenic/likely pathogenic variants (PVs)compared to non-carriers. We investigated the association between extended ET (eET) versus standard-duration ET and clinical outcomes in gBRCA PV carriers with HR+/HER2- EBC. Methods This cohort study derived from an institutional database, including all consecutive patients with BC who underwent genetic counselling at the European Institute of Oncology (May 2002-Jan 2024). Eligible patients had stage I-III HR+/HER2- EBC diagnosed between Jan 2000 and Dec 2022, received adjuvant ET and had complete treatment and follow-up data available. eET was defined as therapy administered for more than 5 years. Primary endpoints were distant relapse-free interval (DRFI) and invasive disease-free survival (iDFS), as defined by STEEP 2.0 criteria. Survival analyses were conducted using univariate and multivariate Cox proportional-hazard models, stratified by year of diagnosis, use of (neo)adjuvant chemotherapy, nodal status, tumor size and grade, stage, ET duration and type BC surgery and BRCA PVs. Left-truncated models were used to account for the interval between BC diagnosis and genetic testing. Landmark analysis was performed to calculate the cumulative incidence of events over time. Results Among 1,225 eligible patients, the median duration of adjuvant ET was 60 months (IQR 49-74), with a median age of 41 years (IQR 36-47). The majority were premenopausal (79%, n=973), and 42% had stage I disease. Sixty percent received eET and 80% received LHRH agonists. Over half received tamoxifen, while 33% received aromatase inhibitors (AI), and 14% switched from tamoxifen to AI. Overall, 164 patients (13%) were gBRCA1/2 PV carriers, mostly gBRCA2 (76%). Carriers were younger than non-carriers (39 years, IQR 35-44 vs. 42 years, IQR 36-48), and more likely to have higher tumor stage (68% vs. 56% stage II/III) and grade (53% vs. 25% grade 3), to receive adjuvant chemotherapy and mastectomy, and to undergo BRCA testing earlier. The median duration of ET was similar in both groups, although a smaller proportion of BRCA PV carriers received eET compared to non-carriers (54% vs. 61%). At a median follow-up of 11.1 years (IQR 8.2-15.2), extended ET was associated with significantly improved iDFS (adjusted HR aHR 0.31, 95% CI 0.26-0.39, p0.001) and DRFI (aHR 0.29, 95% CI 0.22-0.38, p0.001), compared to standard-duration ET. BRCA PVs status was associated to reduced iDFS (aHR 1.5, 95% CI 1.14-1.96, p=0.003), but not with DRFI. In the subgroup of BRCA PV carriers, with a median follow up of 12.3 years (IQR 9.3 vs 15.4), eET remained significantly associated with improved iDFS (aHR 0.30, 95% CI 0.18-0.49) and DRFI (aHR 0.34, 95% CI 0.17-0.65) compared to ET of 5 years or less. Landmark analysis showed that eET was consistently associated with improved DRFI at 60 months (aHR 0.21, 95% CI 0.13-0.33, p0.001), 84 months (aHR 0.27, 95% CI 0.18-0.43, p0.001), and 120 months (aHR 0.57, 95% CI 0.37-0.89, p=0.013). Conclusions In this cohort of BRCA PV carriers with HR+/HER2- EBC, extended adjuvant ET (5 years) was significantly associated with improved invasive disease-free survival and distant relapse-free interval compared to 5 years of ET. These findings support the potential benefit of prolonged endocrine therapy in this high-risk population. Citation Format: P. Zagami, A. Marra, S. Perazzo, C. Grazia, A. Carnevale Schianca, B. Malagutti, E. Giordano, M. Calvello, M. Marabelli, D. Trapani, N. Fusco, E. Guerini Rocco, S. Gandini, E. Munzone, A. Guerrieri-Gonzaga, B. Bonanni, G. Curigliano. Impact of Duration of Adjuvant Endocrine Therapy on Clinical Outcomes in BRCA pathogenic variant Carriers with HR+/HER2- Early Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD4-09.

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