The prevalence of luminal B subtype is higher in older postmenopausal women with ER+/HER2- breast cancer and is associated with inferior outcomes

Abstract

Objectives: To establish whether clinicopathologic and genomic characteristics may explain the poor prognosis associated with advanced age in ER+/HER2- breast cancer.

Materials and methods: The cohort included 271 consecutive post-menopausal patients with ER+/HER2- invasive breast cancer ages 55 years and older. Patients were categorized as "younger" (ages 55- < 75) and "older" (ages ≥75). The Kaplan-Meier method was used to estimate locoregional recurrence (LRR), recurrence-free interval (RFi), and overall survival (OS). Gene expression of tumor samples was assessed with Affymetrix Rosetta/Merck Human RSTA microarray platform. Differential gene expression analysis of tumor samples was performed using R package Limma.

Results: 271 breast cancer patients were identified, including 186 younger and 85 older patients. Older patients had higher rates of Luminal B subtype (53% vs 34%) and lower rates of Luminal A subtype (42% vs 58%, p = 0.02). Older patients were less likely to receive chemotherapy (9% vs 40%, p < 0.001) and hormone therapy (71% vs 89%, p < 0.001). For cases of grade 1-2 disease, older patients had a higher proportion of the luminal B subtype (49% vs. 30%, p = 0.014). Age ≥ 75 predicted for inferior OS (HR = 3.06, p < 0.001). The luminal B subtype predicted for inferior OS (HR = 2.12, p = 0.014), RFi (HR 5.02, p < 0.001), and LRR (HR = 3.12, p = 0.045). There were no significant differences in individual gene expression between the two groups.

Conclusion: Women with ER+/HER2- breast cancer ≥75 years old had higher rates of the more aggressive luminal B subtype and inferior outcomes. Genomic testing of these patients should be strongly considered, and treatment should be intensified when appropriate.

Keywords: Breast cancer; Elderly; Gene expression; Luminal A; Luminal B; PAM50.