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Background: oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. Methods: all available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki67 2wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. Findings: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki67 2wk (p2wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. Interpretation: our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse. Funding: Cancer Research UK (CRUK/07/015).

Hospital-based breast cancer follow-up provides reassurance to patients despite limited evidence for clinical efficacy. Although alternative models of hospital/community-based follow-up have yielded encouraging results, traditional hospital follow-up continues to be offered to all patients. Survival rates continue to rise; consequently, more patients are likely to require support, as many have a limited understanding of the long-term physical and emotional consequences of cancer and its treatment. We examine levels of psychological distress in breast cancer patients in follow-up 2 years or more from diagnosis.This prospective study measured psychological distress levels using standardized measures [Hospital Anxiety and Depression Scale (HADS), Clinical Outcomes for Routine Evaluation (CORE) and Measure Yourself Medical Outcomes Profile (MYMOP)]. Between January and September 2008, 323 consecutive patients were approached in outpatient clinics. Ninety-six patients declined to participate.Two hundred twenty-seven patients took home patient information sheets; 172 (75%) returned completed questionnaires to assess levels of distress (HADS, CORE). MYMOP provided self-reported data on patient symptoms. Patients reported low levels of distress in hospital-based follow-up, which were comparable or better than general population norms, although there was a significant minority of patients reporting high scores (n = 27, 15.7%) on HADS or CORE. There was good agreement between these two measures. All sub-scales of CORE (except risk) correlated well with HADS for anxiety/depression. No significant changes were detected in the standardized measures. MYMOP results showed that 23.8% of respondents reported both physical and emotional symptoms.Breast cancer survivors reported good psychological outcomes 2 years on from diagnosis. Screening for psychological/emotional distress is a vital part of follow-up care, which should be incorporated into UK policy.