HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

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 (Ki672wk). 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 Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. 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

SAFETY OF LIPOFILLING AS A SECONDARY PROCEDURE IN BREAST RECONSTRUCTION

Lipofilling is a useful surgical technique for breast reconstruction following cancer surgery. It has a unique place in the correction of both lumpectomy and post-mastectomy reconstruction defects. The procedure is mostly performed as lipofilling without ADRC. In this study, we included patients who had lipofilling with or without ADRC. We divided patients into two groups. Group I comprised of patients with lipofilling for lumpectomy defects and group II included patients with post mastectomy reconstruction defects. We compared the outcome of lipofilling with or without ADRC. The mean time from oncological surgery to the fat grafting procedure was 58 months (range 20 months to 17 years). An average of 232 ml of fat (80-420 ml) was injected. No immediate postoperative complications were seen. The average follow-up was 50 months following lipofilling procedure. Benign imaging changes were observed in 18/53 (33 percent) patients. A percutaneous biopsy was required in 6 patients (11.3%). No local recurrences were seen in either group of patients. Our results suggested no increase in the risk of local recurrence or new cancer development following lipofilling in breast cancer patients. Patients with stage III disease were found to be at a higher risk of distant metastasis