Age and Late Recurrence in Young Patients With ER–Positive, ERBB2-Negative Breast Cancer

Abstract

Young patients with breast cancer with estrogen receptor (ER)-positive, ERBB2-negative tumors have a poor prognosis. Understanding factors influencing late recurrence is crucial for improving management and outcomes. To determine whether age is an independent factor associated with late distant recurrence (DR) in young patients with ER-positive, ERBB2-negative cancers without distant metastasis within 5 years from surgery. This multicenter retrospective cohort study analyzed clinical records of patients with breast cancer who underwent surgery from January 2000 to December 2011 with at least 5 years of follow-up. The study was conducted at Samsung Medical Center, Gangnam Severance Hospital, and Seoul National University Hospital, including patients aged 45 years or younger with ER-positive, ERBB2-negative tumors, no DR within 5 years after surgery, no neoadjuvant chemotherapy, and at least 2 years of endocrine therapy. The data analysis period was from January 4, 2023, to March 21, 2024. Age, grouped as 21 to 35 years, 36 to 40 years, and 41 to 45 years. The primary outcome was the incidence of late DR at 5 to 10 years after surgery. Survival outcomes, including late distant metastasis-free survival (DMFS), were evaluated in different age groups. Among 2772 patients included, 370 (13.3%) were aged 21 to 35 years, 885 (31.9%) were aged 36 to 40 years, and 1517 (54.7%) were aged 41 to 45 years. The median (range) follow-up was 10.8 (5.0-21.4) years. The youngest group had a poorer histologic grade (eg, histologic grade 3: 107 patients aged 21-35 years [28.9%]; 149 patients aged 36-40 years [16.8%]; 273 patients aged 41-45 years [18.0%]) and more frequent chemotherapy (307 patients aged 21-35 years [83.0%]; 697 patients aged 36-40 years [78.8%]; 1111 patients aged 41-45 years [73.2%]). The youngest patients had significantly worse rates of locoregional recurrence-free survival (patients aged 21-35 years, 90.1% [95% CI, 86.8%-93.3%]; patients aged 36-40 years, 94.6% [95% CI, 93.0%-96.2%]; patients aged 41-45 years, 97.7% [95% CI, 96.9%-98.5%]), disease-free survival (patients aged 21-35 years, 79.3% [95% CI, 75.0%-83.9%]; patients aged 36-40 years, 88.7% [95% CI, 86.5%-91.0%]; patients aged 41-45 years, 94.4% [95% CI, 93.2%-95.7%]), and late DMFS (patients aged 21-35 years, 89.3% [95% CI, 86.0%-92.9%]; patients aged 36-40 years: 94.2% [95% CI, 92.5%-95.9%]; patients aged 41-45 years: 97.2% [95% CI, 96.3%-98.1%]) but not overall survival (patients aged 21-35 years, 96.9% [95% CI, 95.0%-98.9%]; patients aged 36-40 years, 98.2% [95% CI, 97.2%-99.2%]; patients aged 41-45 years, 98.9% [95% CI, 98.3%-99.5%]). Multivariable analysis showed lower hazard for late DR in the older groups compared with the youngest group (age 36-40 years: hazard ratio, 0.53; 95% CI, 0.34-0.82; P = .001; age 41-45 years: hazard ratio, 0.30; 95% CI, 0.20-0.47; P < .001). In this retrospective cohort study, age was an independent factor associated with late DR in young patients with ER-positive, ERBB2-negative breast cancer. Younger age was associated with worse locoregional recurrence-free survival, disease-free survival, and late DMFS, highlighting the importance of long-term monitoring and potential for personalized treatment approaches based on age, particularly for younger patients with ER-positive, ERBB2-negative breast cancer.