<i>CCND1</i> amplification and breast cancer–specific survival in estrogen receptor–positive, HER2-negative disease.

Abstract

e12723 Background: Amplification of Cyclin D1 ( CCND1 ) is common in estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER⁺/HER2⁻) breast cancer and has been implicated in resistance to hormone therapy. However, the prognostic value of CCND1 amplification in clinically defined luminal breast cancer treated with hormone therapy remains unclear. This study evaluated the association between CCND1 amplification and breast cancer–specific survival (BCSS) in Luminal A and Luminal B breast cancer. Methods: For this retrospective cohort study, patients were identified from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. Analyses were restricted to ER⁺/HER2⁻ Luminal A and Luminal B tumors treated with hormone therapy, with or without chemotherapy. CCND1 amplification was defined as a GISTIC copy-number score ≥+2. The primary endpoint was BCSS, defined as time from diagnosis to breast cancer–specific death, with other deaths censored . BCSS was estimated using Kaplan–Meier methods and compared with log-rank tests. Multivariable Cox proportional hazards models adjusted for histologic grade, tumor size, and lymph-node status were constructed. Sensitivity analyses included restriction to patients treated with hormone therapy alone and those with ≥12 months of follow-up. Results: Among 751 eligible patients, CCND1 amplification was present in 22%. On Kaplan–Meier analysis, five- and ten-year BCSS were 79% and 62% in amplified tumors versus 90% and 78% in non-amplified tumors, respectively (log-rank P &lt; 0.001). CCND1 amplification was associated with worse BCSS in the primary cohort (hazard ratio [HR] 1.64; 95% CI, 1.22–2.27; P = 0.002). This association persisted in patients treated with hormone therapy alone (HR 1.76; 95% CI, 1.27–2.44; P &lt; 0.001) and in those with ≥12 months of follow-up (HR 1.66; 95% CI, 1.22–2.27; P = 0.001). Subtype-specific analyses suggested a stronger association in Luminal A tumors than in Luminal B tumors. Conclusions: CCND1 amplification is associated with reduced BCSS in ER⁺/HER2⁻ luminal breast cancer treated with hormone therapy. These findings support further evaluation of CCND1 copy-number status as a prognostic marker in luminal breast cancer.