Aims/hypothesis We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome. Methods A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome. Results Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements; no side effects from the intervention were identified. HOMA-IR came down from 3.1±1.8 to 1.9±1.3 (p<0.001) in the L-AGE group, while it increased from 2.9±1.2 to 3.6±1.7 (p<0.002) in the Reg-AGE group. Conclusions/interpretation L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat ‘at-risk’ obesity. Trial registration ClinicalTrials.gov NCT01363141 Funding The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231)

High sAGEs, a modifiable risk factor for IR, may indicate risk for the MS, type 2 diabetes, and cardiovascular disease. High dietary AGE consumption and serum AGE levels may link healthy obesity to at-risk obesity.

1066 Background: The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), with an anti-estrogen, are the standard of care for HR+/HER2- MBC. Insights from patient biopsies and preclinical analysis suggest that AKT1 activation can provoke CDK4/6i resistance. We hypothesized that targeting AKT1 following CDK4/6i progression may provide clinical benefit. Methods: TAKTIC is an open-label phase Ib trial exploring the combination of the AKT1 inhibitor, ipatasertib (ipat), with an aromatase inhibitor (Arm A), fulvestrant (Arm B), or the triplet combination (Arm C) of fulvestrant + ipat + palbociclib (palbo). The primary objective is to evaluate the safety and tolerability of ipat in combination with endocrine therapy +/- CDK4/6i. Key inclusion criteria include unresectable HR+/HER2- MBC; at least 1 prior therapy for MBC including any CDK4/6i; up to 2 prior lines of chemotherapy for MBC (no limit on prior endocrine therapy). Here, we present an interim analysis from the triplet combination (Arm C). Results: As of 1/31/2020, 25 pts have enrolled, including 12 on Arm C, all of whom received prior CDK4/6i (median no of prior lines = 5.5, range 2-7). Along with fulvestrant, 3 pts received ipat at 200mg + 125mg palbo, 7 pts received 300mg + 125mg palbo, and 2 pts received 400mg + 100mg palbo. To date, 8/12 pts remain on treatment including 2 with partial response, 3 with stable disease, 3 with restaging studies pending and 4 with progressive disease. The triplet combination was well tolerated. Grade 3 toxicities included reduced WBC (8/12), reduced neutrophil count (11/12), reduced lymphocyte count (2/12) and single instances of transaminitis, rash, and reduced platelet count. The only grade 4 toxicity was reduced neutrophil count (4/12). There were no DLTs observed and no discontinuations due to toxicity. Mean steady state pharmacokinetic parameters for ipat were similar to historical data from single agent trials suggesting that combined treatment with palbo + fulvestrant did not affect the pharmacokinetics of ipat. Updated analysis will be presented at the meeting. Conclusions: The triplet combination of endocrine therapy with CDK 4/6i and AKTi appears to be well tolerated in heavily pre-treated pts, with a subset demonstrating signs of clinical benefit. The trial demonstrates how insights into the molecular mechanisms of CDK4/6i resistance could be leveraged into actionable therapeutic regimens for HR+/HER2- MBC. Clinical trial information: NCT03959891 .

Nine of 216 identified studies were selected. Studies exploring patient willingness to undergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.

Research Biopsies in Oncology – Patient Willingness, Perceptions, Understanding, and Experience: An Integrative Review. Background Tumors are classified into subsets based on molecular alterations to select personalized therapies, and research biopsies are essential to advance personalized medicine. However, research biopsies can be associated with complications, results might not directly benefit the patient particularly on-treatment biopsies obtained for evaluation of pharmacodynamics effect, and mandatory requirement can impact patient enrollment in clinical trials. Understanding patient perceptions and experiences surrounding research biopsies may highlight areas for improvement and could expand participation in clinical trials. Objectives The purpose of this integrative review explores and summarizes the current literature on oncology patient perceptions, willingness and experience of research biopsies evaluates data to determine potential implications for practice improvement, patient experience, and clinical trial participation. Methods Articles from January 2010-February 2016 were retrieved via a systematic search restricted to English of MEDLINE/Ovid. Search terms included breast cancer, cancer, research, biopsy, perceptions and attitudes. Inclusion criteria were studies that included patients with cancer and had information on patient willingness, perceptions, understanding, attitudes, and/or experience around research biopsies. Abstracts were independently reviewed for inclusion by two authors. For each selected manuscript, the following information was abstracted: primary author, sample and setting, results, conclusion, and assessment of strength of evidence level and quality using John Hopkins Nursing Evidence Based Practice (JHNEBP) Rating Scales. Results The search resulted in 175 unique studies. 17 abstracts were selected for full manuscript review. From these, 8 were excluded for not meeting inclusion criteria. The 9 selected studies ranged in sample size from 10-362 and all articles were rated IIIA-B evidence level. The majority of studies (66.7%) focused on breast cancer patients. Studies exploring patient willingness to undergo research biopsies (N=8) revealed variability in patient willingness to undergo research biopsies and identified research biopsies identified as a potential barrier to clinical trial participation. Studies exploring patient understanding of the risks and benefits of research biopsies (N=3) revealed overall poor understanding among patients. One study explored anxiety surrounding the research biopsy procedure, suggesting significant anticipatory anxiety is a significant concern. Issues surrounding informed consent were raised in several studies. Conclusions Research biopsies can be associated with significant anxiety, potentially impact enrollment in clinical trials, and consequently there is a need for development of strategies to improve patient experience and education. While a separate consent for research biopsies may be onerous, tailored educational materials, focus groups, as well as development of alternate strategies such as liquid biopsies, are essential to ensuring advancement in cancer care and outcomes. Key Words: cancer, research, biopsy, perceptions, attitudes. Citation Format: Abraham E, Spring L, D'Alleva J, Malvarosa G, Tripp E, Post K, Bardia A, Habin K. Research biopsies in oncology-patient willingness, perceptions, understanding, and experience: An integrative review [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-20-07.