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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).

Coping strategies used by women with breast cancer are vital for adjustment to their disease. Whilst it is clear that factors such as age at diagnosis, social support and ethnicity can influence coping mechanisms, there is currently no information about whether breast reconstruction changes mechanisms of coping for such patients. The aims of this study, therefore, were to determine how women who have had immediate breast reconstruction and mastectomy cope, compared to those who have mastectomy alone, and whether there are differences in coping mechanisms due to breast reconstruction surgery. This was a retrospective cohort study, using a standardised questionnaire called the Brief Cope Scale. Inclusion criteria was the following: all women who had immediate breast reconstruction and mastectomy in Shropshire from 2003 to 2014 for ductal carcinoma in situ or node-negative invasive breast cancer. Each patient was matched for year of diagnosis, adjuvant therapy and age to one woman who had mastectomy alone. Two hundred thirty-four questionnaires were sent with a 58% response rate. Significantly more patients from the reconstruction cohort coped by active coping (T value 1.66, P value 0.04) compared to those in the mastectomy alone cohort. In contrast, significantly more patients in the mastectomy alone cohort coped by active venting compared to the reconstruction cohort (T value 1.71, P value 0.04). This study indicates for the first time that breast reconstruction may alter coping mechanisms in breast cancer survivors. Awareness of these coping mechanisms will enable clinicians to provide appropriate, individualised support.

The phenomenon of limb regeneration is briefly described, and factors empirically known to enhance regeneration are reviewed. Regeneration is compared to the initial development of the limb, with which it shares many similarities. Recent advances in understanding of the control mechanisms underlying regeneration are described; in particular, the role of retinoids, and their relationship with homeobox-containing genes are considered. The long-term prospects of inducing regeneration in human amputees are considered, and a cautious “thumbs up” is given to this notion, at least in a limited form.