Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Abstract

Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers.

Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and "other". The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes.

Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4-43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2-68.6). Patients with MA and TN basal-like tumours have lower survival outcomes.

Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered.

Fig. 1

Recurrence-free interval in the molecular apocrine subtype (any HER2 status, HER2-positive and HER2-negative subgroups). HR hazard ratio, CI confidence interval, MA molecular apocrine, HER2− human epidermal growth factor receptor 2 negative, HER2+ human epidermal growth factor receptor 2 positive

Fig. 2

Recurrence-free interval in the six subtypes. HR hazard ratio, CI confidence interval, lum A luminal A, lum B luminal B, HER2– human epidermal growth factor receptor 2 negative, HER2+ human epidermal growth factor receptor 2 positive, MA molecular apocrine, TN triple negative

Fig. 3

HER2, AR and ESR1 gene expression of individual tumours labelled by LAB class. a HER2 and ESR1; b AR and ESR1. The points are coloured according to the LAB classification. The gene expression units are arbitrary Affymetrix signal intensities after normalisation with the rma algorithm. HER2 human epidermal growth factor receptor 2, AR androgen receptor, ESR1 oestrogen receptor 1, L luminal, B basal, MA molecular apocrine