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Introduction The risk of breast cancer increases with age and our global population is ageing. By 2040 the number of breast cancer cases diagnosed per year worldwide will double and over 40% of these will be in patients aged 70 or over. Despite this, there are few treatment guidelines specific to breast cancer in older women and none which consider the unique biological differences of this cohort. Method Surgical and core needle biopsy (CNB) specimens were obtained from an existing series of 1,785 women over the age of 70 with primary breast cancer, treated in a single institution with long-term (37+ years) follow-up. Of this cohort, 813 had primary surgical treatment. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and 693 CNB specimens. Immunohistochemical staining for 32 biomarkers has been performed in all of the available TMAs. Association between histological score for each biomarker and tumour size, grade, recurrence rate, breast cancer specific and overall survival is currently being investigated in the whole cohort. Results Results to date have revealed a unique biological cluster in older women with primary breast cancer that is not seen in a comparative younger cohort. In the future, bioinformatics analysis will determine which biomarkers and in what combination, can predict chance of recurrence/overall survival in this cohort. Conclusions This information will be used to create a prognostic tool specific to assist older women with decision making regarding primary treatment of breast cancer.

This abstract was withdrawn by the authors. Citation Format: Athanasiou I, Reed MW, Shrestha A, Cheung K-L, Audisio R, Collins K, Wyld L. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-06.

Background: Capivasertib (AZD5363), an AKT1,2,3 inhibitor, significantly improved progression-free and overall survival when added to paclitaxel in triple negative breast cancer (BC) patients (Schmid et al. ASCO 2018). We have previously reported in STAKT, robust target inhibition at 480mg BD versus placebo, including significant decreases in the primary biomarkers (PBs) - Ki67, pPRAS40 & pGSK3β - in primary BCs (Robertson et al. SABCS 2017). We now report the dose- and exposure-response relationship of capivasertib and the correlation between primary and secondary (pAKT, pS6, nuclear FOXO3a) tumor biomarkers. Design: STAKT was a two-stage, double blind, randomized, placebo controlled 'window-of-opportunity' trial in newly diagnosed ER+ BC patients. Stage 1 assessed capivasertib at a dose of 480mg BD p.o. versus placebo. Stage 2 assessed capivasertib at two lower doses 360mg and 240mg BD. Tumor biopsies were taken prior to 1st dose and after 4.5 days of dosing. Evaluable patients (who required pre-defined minimum baseline PD values for PBs) included placebo (n=11), capivasertib at 480mg (n=17), 360mg (n=5) and 240mg (n=6). Blood samples for pharmacokinetic (PK) studies were scheduled at pre-dose; 2, 4, optional 6 & 8 hrs post first dose on Day 1; ˜2-4 h post last dose on Day 5 (before biopsy). The % change from baseline for PBs were evaluated against the following exposure variables (placebo=0): i) Dose, ii) Observed Cmax Day 1 (˜2h post-dose), iii) Observed plasma concentration on Day 5, iv) Model-predicted plasma concentration Day 5 at time of biopsy, and v) Model-predicted AUC on Day 5. Spearman correlation coefficient measured the strength and direction of association between biomarkers. Results: · Significant mean reductions in % change from baseline were observed for the PBs pGSK3β (-39%; p · Dose-response relationships for individual % change from baseline could be described by an Emax model for all PBs. Overall, the correlation to PK exposure (observed or predicted) was similar to the correlation to dose. · Correlation coefficient analyses between biomarkers at capivasertib 480mg BD identified- i) Positive correlations for pGSK3β with Ki67 (ρ = 0.52, p-value < 0.05) & with pS6 (ρ = 0.54, p-value Conclusions · Capivasertib caused dose- and concentration- dependent effects on biomarkers after only 4.5 days. · Significant changes in the PBs were demonstrated at 480 mg BD. Biomarker changes was observed at 360mg and 240mg BD, but statistical analysis was limited by the small sample size at lower doses. · Correlation between a number of tumor biomarkers (relative changes) were identified for capivasertib 480mg BD. Citation Format: Gee J, Coleman RE, Cheung KL, Evans A, Holcombe C, Skene A, Rea D, Ahmed S, Jahan A, Horgan K, Rauchhaus P, Littleford R, Finlay P, Cheung A, Cullberg M, de Bruin E, Foxley A, Koulai L, Pass M, Schiavon G, Rugman P, Deb R, Robertson JFR. Dose- and exposure-response relationship and biomarker correlation analysis in breast tumors from patients treated with capivasertib, an AKT inhibitor, in the STAKT randomized, placebo controlled pre-surgical study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-12-01.

Photovoltaic (PV) is one of the promising solar energy applications. Measured data can give the realistic performance of PV systems under actual operating environments for product selection and system design. This paper studies a grid-connected PV system installed in an institutional building. Technical data including available solar radiation and output energy generated were systematically recorded and analyzed. The performance of the PV system is elaborated in terms of energy, environmental and financial aspects. Feed-in-tariff (FIT) schemes with high electricity selling price can encourage the deployment of PV system. The monetary payback period (MPBP) for the PV system was computed to be 72.4 years when the electricity buying price is equal to the electricity selling price. If carbon trading was considered, the payback was shortened to 61.4 years. The embodied energy payback period (EEPBP) was estimated to be 8.9 years. The findings would be useful for planning grid-connected PV installations and applicable to other spaces with similar architectural layouts.

Background: AKT is an important intracellular control point through which Type 1 growth factors and IGFR signal. Mutations in PIK3CA, AKT and PTEN are prevalent in estrogen receptor positive (ER+) breast cancer (BC) and have been implicated in resistance to endocrine therapies. AZD5363 is an inhibitor of AKT 1, 2 and 3 currently in Phase 2 trials for BC and other solid cancers. Design: The study examined whether AZD5363 impacts on key biomarkers within the AKT pathway and their subsequent effects on Ki67, a marker of tumor proliferation. STAKT is a multi-center, two-stage, double blind, randomized, placebo controlled, biomarker 'window-of-opportunity' trial in women with newly diagnosed, previously untreated ER+ BC who were deemed would require chemotherapy as part of their primary treatment regimen. Stage 1 assessed AZD5363 at a dose of 480mg bd p.o. versus matching placebo. Up to 30 patients per arm were permitted, to allow 12 subjects per arm with evaluable paired biopsies - obtained at baseline, and after 4.5 days of AZD5363 / placebo. Primary endpoint markers were pPRAS40, pGSK3β and Ki67 assessed by immunohistochemistry. pPRAS40 and pGSK3β were assessed by H-scores and measured separately for cytoplasmic (cyto), nuclear (nuc) and total (cyto+nuc) staining. Ki67 was assessed as % positive staining of 500 tumor nuclei. Laboratory staff were blinded to treatment arm and whether the biopsies were taken before or after AZD5363/placebo. Changes in marker expression (both absolute and %) between biopsies were calculated, and compared between the two groups. An ANOVA test was applied for normally distributed data and Wilcoxon Mann-Whitney used if not normally distributed. Results: 28/36 patients were evaluable with patient & tumor characteristics as follows: 17 received AZD5363 and 11 placebo; the median ages were 48 & 49 years respectively. 27 patients were Caucasian and 1 African-American. Tumors were all ER+. For HER2 status 8 were positive & 9 negative in the AZD5363 treated group compared to 2 & 9 respectively in the placebo group. For pPRAS40 and pGSK3β cyto was the predominant staining while for Ki67 staining was nuclear. Changes in each marker with associated p-values are shown in the table. MarkerType of change vs baselineDegree of change in AZD5363 arm (n=17)p-value versus placebo arm (n=11)pPRAS40 (H-score)TotalAbsolute-83.8 Conclusions• AZD5363 for 4.5 days caused highly significant falls in pGSK3β and pPRAS40, key markers of AKT pathway activation • AZD53643 also caused a significant decline in Ki67 even after only 4.5 days of drug. This is one of the shortest 'window'-studies to report such an early effect on proliferation. • Placebo controlled 'window' studies of this short duration can provide important evidence of the therapeutic potential early in a drug's development. Citation Format: Robertson JFR, Coleman RE, Cheung KL, Evans A, Holcombe C, Skene A, Rea D, Ahmed S, Jahan A, Kelly S, Horgan K, Rauchhaus P, Littleford R, Foxley A, Lindemann JPO, Pass M, Rugman P, Deb R, Finlay P, Gee JMW. AZD5363, an AKT inhibitor, significantly inhibits key biomarkers of the AKT pathway and Ki67, in a randomized, placebo, controlled study (STAKT) in human breast cancers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-06.

Electric lighting is one of the major energy consuming items in many non-domestic buildings. Using appropriate energy-efficient light fittings with dimming controls and proper daylighting schemes can help reduce the electrical demand and contribute to visual comfort and green building development. This paper presents a study on the energy and lighting performances for energy-efficient fluorescent lamps associated with electronic ballasts and high frequency photoelectric dimming controls installed in a school building. Electricity expenditures and indoor illuminance levels for a workshop and a classroom employing high frequency dimming controls were analyzed. Simple prediction methods were used to illustrate the lighting savings. The findings provide the operational and performance information, which would be applicable to other spaces with similar building layouts and lighting schemes.

Sustainability is the trend of the modern building designs, in which solar energy conversion systems and daylighting schemes are widely considered as the important building energy strategies to reduce the peak cooling and electrical demands, generate clean energy and save the building electricity expenditures. A semi-transparent photovoltaic (PV) is a renewable energy product producing electricity via solar cells and allowing natural light entering into the interior spaces for daylighting designs. The PV modules are effective in reducing the cooling demand, especially for the skylight atrium that often receives large solar heat gains. This paper studies the thermal and visual properties, energy performance, environmental and financial issues of such semi-transparent PV skylights. Field measurements including solar irradiance, daylight illuminance and electricity generated were carried out. Case studies based on a circulating atrium were conducted to evaluate the energy use, cooling requirements and monetary implications when the PV skylights together with the daylight-linked lighting controls were applied. The results indicated that such an integrated system could save the overall electricity expenditures and benefit to the environmental and financial aspects.

Principal component analysis of dry-bulb temperature, wet-bulb temperature, global solar radiation, clearness index and wind speed was conducted, and a two-component solution obtained which could explain 80% of the variance in the original weather data. Clustering analysis of these two principal components resulted in a total of 18 typical day types being identified. A year long monitoring of the daily chiller plant electricity consumption in a fully air-conditioned office building was conducted. It was found that the typical day types exhibited daily and seasonal variations similar to the daily and monthly electricity consumption recorded. Three regression models were developed to correlate the daily chiller plant electricity consumption and the corresponding day types. The coefficient of determination (R2) was 0.86–0.99 showing strong correlation. It is proposed that the day type approach can be used as a tool for weather normalisation and inter-year comparisons in the analysis of energy savings due to building retrofits. It was also found that the typical day types identified appeared to show a slight increasing trend during the 28-year period (1979–2006) indicating a subtle, but gradual change of climatic conditions that might affect chiller plant electricity consumption in future years.

Two-parameter regression models were used to predict global solar radiation (GSR) for the nine major thermal zones and sub-zones – severe cold (I, II and III), cold (I, II and III), hot summer and cold winter, mild, and hot summer and warm winter – across China. The impact of using modelled GSR on building energy simulation was investigated. A total of nine cities were selected, one for each thermal zone. Generic office buildings were developed for each of the nine cities according the local design/energy codes. Two sets of energy simulation were conducted for each city, one with the measured GSR and the other the modelled data. The computed results were analysed in four aspects – solar heat through the windows, building heating loads, building cooling loads and the corresponding building energy consumption. It was found that simulated annual heating/cooling loads could differ by 0.1–6.2% and total building energy consumption 0.1–1.2%. These differences were also compared with the mean bias error and root-mean-squared error of the modelled GSR.

Sensitivity analysis is performed to observe the response of the system when a given design parameter is changed. It is important to know the relationships between the input parameters and output results such that appropriate design variables can be selected to achieve the optimum building energy performance. This paper studies the sensitivity of energy performance and establishes regression models for office buildings with daylighting designs in Hong Kong. The building energy simulation computer program, namely EnergyPlus, was used to generate data for the analysis. The important input design parameters affecting the daylighting schemes were identified and analysed in terms of annual building electricity expenditures and peak electrical demands. Four building envelope design parameters, namely, window-to-wall ratio, light transmittance of windows, projection ratio of overhang, and projection ratio of side-fins were found to correlate well with the predicted incremental electricity use (IEU) and incremental peak electricity use (IPEU). Both linear and non-linear multiple regression techniques were used to develop regression models and energy equations for the predictions of IEU and IPEU. Statistical results show that such models and equations can be used to evaluate the energy performance of various building envelope design schemes for building with daylighting controls during the early design stage.

There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of human epidermal growth factor receptor-2 (HER2) overexpressing tumours in older women. Currently, research involving trastuzumab at large focuses on the younger population. This study aimed to analyse their biological characteristics and to compare them with their younger counterparts from a single centre with a long-term clinical follow-up.Over 37 years (1973-2010), 1758 older (≥70 years) women with early operable (5 cm) primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these, 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray analysis using indirect immunohistochemistry. Comparison was made with data from a well-characterised younger (70 years) series (N = 1711) treated between 1986 and 1998 (before adjuvant trastuzumab became standard) in our institution. Forty five (7.6%) and 140 (8.2%) patients from the older and younger series, respectively, had HER2-positive tumours.HER2 overexpression was seen in 45 (7.6%) older women and 140 (8.2%) in younger patients (P = 0.56). HER2 overexpressing tumours in older women when compared with that in their younger counterparts were associated with low Ki67 and high bcl2 expression (P0.05). Only 26% of the younger patients and none of the older patients received adjuvant chemotherapy, and no patients at the time received trastuzumab. However, there was no significant difference in the outcome of the two age groups (5-year breast cancer-specific survival rate:70 years = 65% versus70 years = 70%, P = 0.51).HER2 overexpressing tumours in older women showed relatively a less aggressive phenotype and did not show any inferior long-term clinical outcome despite not having received chemotherapy when compared with the younger patients. The precise role of different adjuvant systemic therapies in this population needs to be delineated.

We describe an exposure of varicella zoster virus in our neonatal intensive-care unit and the emergency procedures instituted to prevent an outbreak. Fifty-seven infants and 129 staff members were exposed but none developed chickenpox. The measures included rapid identification of varicella antibody status in all neonates and those staff members with uncertain history of varicella infection; cohorting of exposed infants according to immune status; and prompt administration of varicella zoster immunoglobulin to susceptible patients. The recommendation of the American Academy of Pediatrics did not accurately predict the immune status of preterm infants, as only one of the eight susceptible infants would have qualified for immunoglobulin prophylaxis if their guidelines had been followed. Mass screening of all exposed infants using the varicella zoster enzyme linked immunosorbent assay (ELISA) test was the only reliable means of determining the immune status. Of the four risk factors evaluated for the prediction of antibody status: gestational age, postnatal age, birthweight and episodes of blood transfusion, only postnatal age was found to independently predict the immune status of our patients. Because varicella zoster susceptible staff members are difficult to identify on the basis of history, we suggest that prospective screening of staff in high-risk units be undertaken and vaccination with live varicella vaccine be offered to susceptibles.

Track 1 Solid Tumours in the Elderly Breast cancer in eldery patients P001 Decision making in older women with primary operable breast cancer R.M. Parks*, P. Howard, L. Hall, S.-W. Tang, R. Lakshmanan, L. Winterbottom, D. Morgan, D. Porock, K. Cox, K.-L. Cheung. Division of Breast Surgery, Nottingham University Hospitals; School of Nursing, University of Nottingham; NottinghamBreast Institute, Nottingham University Hospitals, Nottingham, UK; Department of Oncology, Nottingham University Hospitals, Nottingham, UK; School of Nursing, University of Buffalo, New York, USA

A pair of preterm twins developed fatal necrotizing enterocolitis (NEC) in association with Staphylococcus epidermidis septicaemia after receiving contaminated expressed breast milk (EBM). S. epidermidis NEC can be associated with severe bowel inflammation, high morbidity and mortality. Breast milk is the most suitable nutrient for preterm infants but EBM should undergo regular screening for bacterial overgrowth. We urge caution before administering EBM found to be heavily contaminated with S. epidermidis to preterm infants.

patients aged ≥70 years. Methods: Between October 2011 and April 2012, 403 patients were included: 171 and 232 patients in the retrospective and the prospective study, respectively. Elderly patients (≥70 years) were analysed separately and their characteristics were compared to the youngest patients (b70 years old). Results: In the retrospective study, 55 elderly patients were analysed. Median age was 78 years [70–94]. Thirty-six (65%) and 8 (15%) patients had hormone-sensitive and HER2-positive tumours, respectively. Seven (7) and 24 patients had exclusive bone and visceral metastases, respectively. Twenty-four (24) patients received oral Navelbine as first line therapy, 27 as second line and 4 beyond second line. The median duration of treatment was 6 months regardless the line of treatment. Oral Navelbine was prescribed as single-agent therapy in 36 patients. In case of combination regimen, oral Navelbine was combined with chemotherapy in 13 patients (capecitabine in 12 patients (22%)) or with a targeted therapy in 6 (mainly trastuzumab). In the prospective study, 84 elderly patients were analysed. Median age was 75 years [70–89]. PS was 0 or 1 in 50 patients, and 65 had at least one comorbidity. Sixty-two (74%) and 79 (94%) patients had hormone-sensitive and HER2-positive tumours, respectively. Exclusive bone metastases were found in 25 patients. The median starting dose of oral Navelbine was 59 mg/m. Singleagent therapy was given in 70 patients (31 patients (37%) and 32 patients (38%) in first and second lines, respectively) whereas 14 patients received a combination regimen, of whom 11 patients (79%) received capecitabine. The monitoring showed that the time to the next scheduled visit was less than 30 days in only 63% of the patients. Conclusion: The results of both retrospective and prospective studies show similar profiles of elderly MBC patients treated by oral Navelbine. In this population, oral Navelbine is often prescribed as single-agent, for the first or the second line and for the same duration regardless of the line. In case of combination, oral Navelbine is most often combined with capecitabine or trastuzumab (in HER2positive patients). Interestingly, the prospective study shows that the follow-up of patients needs to be optimized, a particularly important issue in the setting of an oral chemotherapy schedule in the elderly.

O1 Biological characteristics of triple negative early operable primary breast cancer in older women in comparison with their younger counterparts B.M. Syed, A.R. Green, D.A.L. Morgan, I.O. Ellis, K.L. Cheung*. Division of Breast Surgery, University of Nottingham, Nottingham, UK, Divisions of Pathology, University of Nottingham, Nottingham, UK, Department of Oncology, NottinghamUniversity Hospitals, Nottingham, UK

The radiographic findings in a 57-year-old-man with left aortic arch and right descending aorta are described. Left aortic arch with right descending aorta, first described by Paul in 1948, is a very rare congenital anomaly. To our knowledge only 16 cases have been reported in the English literature. We describe here an additional case to emphasize its existence and supplement the data in the literature.