DNA aneuploidy identifies a subset of Luminal subtype breast carcinoma patients with worse clinical outcome.

Abstract

In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients. The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis. Luminal A subtype had the lowest prevalence of disease recurrences (23.6%) and deaths from disease (18.3%), while Luminal B (42.2%/37.9%), Triple-negative (46.4%/40.6%), and HER2-positive (55.9%/50.0%) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4% of disease recurrences and 17.6% of deaths from disease). Luminal A tumours were mostly diploid (55.3%), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6% and 88.2%, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8% and 70.6%, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes. DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy.