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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).

Introduction: Dual HER2 targeting improved pCR rates (ypT0ypN0) compared with Herceptin plus chemotherapy in the TRYPHAENA and NeoSphere registration trials. Pertuzumab-containing regimens (FEC-THP and TCHP) were adopted at the Kent Oncology Centre (KOC) following national funding approval in December 2016. Methods: A retrospective study of 176 (stage 1-3) HER2+ breast cancer patients receiving HER2-directed NACT at KOC between November 2014- December 2018 was conducted. Single targeting treatment (S) used FEC-TH. Dual targeting (D) regimens were FEC-THP or TCHP. Data was collected on age, stage, grade, HER2 and ER status, treatment regimen, treatment completion, pCR (ypT0ypN0) status, and echocardiogram results. Results: 51 patients received single HER2 targeted FEC-TH prior to funding approval for Pertuzumab. 125 patients received dual HER2 targeted agents (60 FEC-THP, 65 TCHP). A slight excess of ER negative and node positive cancers was seen in the S group. Dual targeting increased pCR rates: 50.4% (D) vs 37.2% (S). Overall, pCR rates did not differ between the two D regimens (50% vs 50.7% for FEC-THP and TCHP respectively). Amongst D treated patients, pCR rates were greater in ER negative tumours with the highest pCR rates seen in those receiving TCHP. For ER positive patients both D regimens modestly increased pCR with no clear benefit to TCHP (table 1). FEC-THFEC-THPTCHPn516065pCR ERpos (%)414745pCR ERneg (%)335471 Early chemotherapy discontinuation rates were similar in both groups but interruptions in trastuzumab (H) treatment were more common in D, particularly the TCHP group (table 2). FEC-THFECTHPTCHPChemo stopped early19% (6)20% (12)20% (13)H stopped early0% (0)3% 2)0% (0)H± Pinterrupted2% (1)6.6% (4)12.3% (8) Conclusion: A substantial increase in pCR rates was observed with dual targeting, regardless of ER and nodal status, reproducing the registration trial data in real world clinical practice. pCR rates were greatest in D treated patients with ER negative cancers, regardless of treatment regimen. TCHP was the most effective D regimen in ER negative patients but did not deliver superior pCR rates to FEC-THP in ER positive breast cancers. Substantially more cardiac toxicity and H treatment interruptions were observed with D, particularly with TCHP therapy. Citation Format: Jessica Little, Samantha Forner, Van Sim, Russell Burcombe, Rema Jyothirmayi, Jennifer Louise Glendenning. The differential impact of non-anthracycline treatment regimens on pathological complete response (pCR) rates by ER status after neoadjuvant single or dual HER2 targeted therapy (NACT): A single centre experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-31.

e14050 Background: Historically, metastatic spinal cord compression (MSCC) referrals trend towards a Friday peak in incidence (Koiter E, Radioth Onc 2013). However, data from a single, tertiary centre in the UK showed a reversal in the Friday peak (Adeleke S, Annals of Oncology 2020). This was attributed to early case referrals and quicker treatment decisions. In this new study, we explored whether a similar pattern was apparent in multiple district general hospital (DGH) settings and attempt to identify underlying causes. DGHs manage a larger proportion of cancer patients in the UK. Methods: 1,069 patients between 1 Jan 2015 and 31 Dec 2020 were identified across 4 hospitals in Kent, UK with a population of 1.6 million people. 220, 181, 182, 159, 134 and 193 MSCC patients were identified annually (2015-2020). Commonest cancers were prostate (24.1%), lung (19.3%) and breast (12.3%). Thoracic and lumbar regions constituted 80% of MSCC sites. Kruskal Wallis was used to compare differences in referrals across weekdays. Data was then dichotomised to Fridays only vs. other days of the week combined, as previously reported (De Bono B, Acta Neurochir 2019). Chi squared was used to compare frequency of referrals between the two groups. Chi squared goodness of fit test was conducted to detect if Friday reflected the day with highest referrals across the week. Results: Across the region, 2015 saw the highest number of Friday referrals relative to other days, p= 0.002. Friday referrals continued to drop, year on year, until 2018 with a corresponding increase in mid-week referrals. After 2018, there was a return in trend to a further Friday peak across the region, though p= 0.836. On an individual hospital basis, the persistent Friday peak in the region was driven by two hospitals. Having a 7-day acute oncology service (AOS), 7-day radiology reporting and single referral point of contact in the department, were factors identified that kept the referrals across the week uniform. On another note, a substantial shift towards a single 8Gy fraction vs. 20Gy in 5 fractions was observed across the region. This change coincided with SCORAD III data (Hoskin P, ASCO 2017) and demonstrates adherence to evidence-based practice in the region. Conclusions: This large multi-centre retrospective study shows a differential referral pattern in the region, with hospitals with 7-day AOS/Radiology reporting and single point of referral (e.g, similar to MSCC coordinator role) having a quicker treatment turnaround and uniform referrals across the week. The MSCC coordinator has been shown to streamline service, ensure timely decision-making and improved survival outcomes (Richards L, Spine J 2017). The role is recommended by NICE UK. DGHs should consider appointing an MSCC coordinator when designing/auditing their service. The shift towards single 8Gy fraction can provide a ‘one-stop’ service where patients are scanned, planned and treated on the same day.

Historically, HER2-positive breast cancer had a poor prognosis. The development of molecul ar ther apies that target the HER2 receptor has TR ansformed outcomes. Here, the evidence on Anti-HER2 therapies is summarised

Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID), over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here, we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c. trastuzumab was delivered via hand-held syringe.Patients were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c. trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa. The primary endpoint was overall preference proportions for s.c. or i.v., assessed by patient interviews in the evaluable ITT population.A total of 245 patients were randomized to receive s.c. followed by i.v. and 243 received i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients, respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI) 85.7-91.6; P0.0001; two-sided test against null hypothesis of 65% s.c. preference]; 45/467 preferred i.v. (9.6%; 95% CI 7-13); 7/467 indicated no preference (1.5%; 95% CI 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled s.c. and i.v. periods, respectively (P0.05; 2 × 2 χ(2)); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5.PrefHer revealed compelling and consistent patient preferences for s.c. over i.v. trastuzumab, regardless of SID or hand-held syringe delivery. s.c. was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared with the known i.v. profile in EBC. PrefHer and HannaH confirm that s.c. trastuzumab is a validated and preferred option over i.v. for improving patients' care in HER2-positive breast cancer.NCT01401166.

Aim: Firstly, to quantify active healthcare professional (HCP) time and costs associated with subcutaneous (SC) administration of trastuzumab (Herceptin?) compared with the standard intravenous infusion (IV) in the treatment of patients with HER2-positive early breast cancer within the adjuvant PrefHer trial setting; secondly, to measure patient time in the care unit and patient infusion chair time for both routes of administration. Methods: A UK multi-centre prospective, observational Time and Motion study was conducted alongside the PrefHer trial (ClinicalTrials.gov id: NCT01401166). Trained observers measured the duration of each SC and IV related task that HCPs undertook and recorded patient time in the chemotherapy unit and infusion chair. The type and quantity of medical consumables used with each route of administration were also collected. Twenty-four patient episodes were recorded (12 SC, 12 IV). Mean total administration time was calculated as the mean sum of task times, both for IV and SC formulations. The mean cost of each route of administration was calculated as the mean cost of HCP time plus the mean cost of consumables used. HCP time was costed using Personal Social Services Research Unit. Consumables were costed using hospital pharmacy data and online sources. Results: Mean active HCP time for IV administration was 92.6 minutes compared with 24.6 minutes for SC administration. The mean cost for IV preparation and administration was ￡144.96 (￡132.05 of HCP time and ￡12.92 of consumables) versus ￡33.15 (￡31.99 of HCP time and ￡1.17 of consumables) for SC administration. Mean time spent in the care unit and in the infusion chair was 94.5 minutes and 75 minutes respectively for IV, and 30.3 minutes and 19.8 minutes for SC. SC administration of trastuzumab could translate to a time saving of 68 minutes (versus IV) with a total cost saving of ￡111.81 per patient episode. This equates to a potential saving of ￡2012.58 over a full course of adjuvant treatment (18 cycles). Conclusion: Substituting IV infusion with SC administration of trastuzumab may lead to a substantial reduction in active HCP time, patient chair and unit time, consumable use and overall costs. The reduced patient chair and unit time could provide increased capacity within existing resources.

Delivering multifaceted, quality care to women living with metastatic breast cancer (MBC) demands professional competence and an advanced level of practice. The breast cancer nursing community is evolving to meet this need as more nurses are appointed specifically for the advanced disease setting, while nurses who previously worked only in early stage disease are now delivering care across the disease trajectory, fulfilling a ‘diagnosis to death’ nursing model.The MBC nursing community, linked by UK charity Breast Cancer Care and the Roche Nursing Matters programme, offers forums for learning, and provides ongoing support to this group of nurses. This supplement has been commissioned by Roche Products Ltd to continue supporting nurses who treat patients with MBC by sharing learning and best practice, with a view to encouraging innovation in service delivery.

Current guidance, nationally and internationally, would suggest within oncology and hospice outpatient settings holistic assessment be completed. However how this should occur and what assessment tool be used, there is no agreed consensus. Aim To explore the use of a validated patient reported symptom assessment tool within a lung oncology and hospice outpatient setting. Methodology An exploratory study looking at patient reported ESAS-r assessment form completion prior to attending their clinic review with an oncology and hospice setting and the data collected, analysed for comparison. Results Total number of Hospice patents: 22 (male13: female 9), age: 42–80 versus total number of Oncology out patients: 26 (male14: female 12), age: 54–91. The median total symptom score for hospice outpatients was 34.5/100 versus median total score for Oncology outpatients was 23.5/100. Tiredness (6.5/10) and drowsiness (5/10) were the high scoring symptoms within hospice outpatients while tiredness (5/10) and wellbeing (5/10) were in the lung cancer outpatient setting. The median score for pain and shortness of breath was 3/10 & 0/10 in Hospice patients versus 1/10 & 1.75/10 in Oncology clinic patients. Conclusion The symptom scores were comparable and not surprisingly the median scores were higher in the hospice outpatient setting. The physical and psychological symptoms scored significantly higher in the hospice outpatient population. The authors acknowledge the small sample size and this was an exploratory piece of work. However, clinicians found the ESAS-r tool to be clinically useful and helped focus discussions about what was important from a patient9s agenda but helped in the disclosure of commonly ignored symptoms such as fatigue. This then prompted further assessment for eligibility for clinical trials specifically directed at fatigue management. Therefore the use of a patient, self-reported holistic assessment tool is a useful addition to oncology and hospice outpatient clinics.

Sarah Jane Mitchell’s devotion to paediatrics started as a student at Queen Elizabeth Hospital for Sick Children. Training in north London, she developed a special interest in neonatology. Her other passion—travel …