<p>Supplementary Figures S1-S5. Supplementary Tables S1-S5. Figure S1. Comparison of SNV mutation signatures across histological and molecular subtypes. Figure S2. Treatment timelines and radiographic outcomes. Figure S3. Mutation signature stability metrics and comparisons to known signatures. Figure S4. Structural variant mutation sigantures. Figure S5. Comparison of mutation burden between aging-driven and non-aging-driven breast tumours. Table S1. Kruskal-Wallis tests. Table S2. HRDetect prediction test metrics. Table S3. Area under the curve of HRD signatures in platinum response prediction. Table S4. Logistic regression model odds ratios of clinical improvement on platinum. Table S5. Accession IDs of genome datasets submitted to the European Genome-Phenome Archive.</p>
<p>Table S5: Data from this study have been submitted to the European Genome-Phenome Archive (EGA) (www.ebi.ac.uk/ega/home) under the study accession number EGAS00001001159. This table provides the accession numbers for each dataset included in this study.</p>
Abstract Background Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof‐of‐concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. Methods Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self‐reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24‐week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self‐report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy–Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. Results Compared to CON, EX had a reduced time to complete a processing speed test (trail making test‐A) (‐14.2 seconds, P < .01; effect size 0.35). Compared to CON, there was no improvement in self‐reported cognitive function and effect sizes were small. Interestingly, lack of between‐group differences in Stroop behavioral performance was accompanied by functional changes in several brain regions of interest in EX compared to CON at 24 weeks. Conclusion These findings provide preliminary proof‐of‐concept results for the potential of aerobic exercise to improve cancer‐related cognitive impairment and will serve to inform the development of future trials.
<p>Kaplan-Meier estimation of overall survival of mCRC patients with BRAFV600E mutations detected by NGS (BRAFNGS) and two IHC (BRAFIHC) subsets: patients that received any NGS testing and patients that were never NGS tested.</p>
e20563 Background: The Personalized OncoGenomics (POG) program at the BC Cancer Agency integrates whole genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examine patients with metastatic NSCLC and report the prevalence of actionable targets, treatments, and outcomes. Methods: Between 2012-2016, 217 patients had a tumor biopsy and blood sample with comprehensive DNA (80X; 40X normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer “drivers” and/or actionable/treatable targets. In NSCLC cases, we compared the progression-free survival (PFS) of “POG-informed therapies” with the PFS of the last regimen prior to POG (PFS ratio). Results: In 29 NSCLC cases, median age was 60.2 years (range 39.4-72.6), 11 were male (38%), and histologies were: adenocarcinoma (93%); squamous cell carcinoma (7%). Potential molecular targets (i.e. cancer “drivers”) were identified in 26 (90%), and 21 (72%) had actionable targets. 13 received POG-informed therapies, of which 3 had no therapy before POG. Of 10 patients with POG-informed therapy, median PFS ratio was 0.94 (IQR 0.2-3.4). 3 (30%) had a PFS ratio ≥1.3, and 3 (30%) had a PFS ratio ≥0.8 and <1.3. Conclusions: In this NSCLC cohort, 30% demonstrated longer PFS with POG-informed therapies. Larger studies will help clarify the role of whole genome analysis in clinical practice. [Table: see text]
227 Background: The decisional conflict scale (DCS) measures personal perception of uncertainty when facing a decision. In patients with cancer, decision conflict is likely when considering uncertainty in oncologic systemic treatment outcomes. Cancer genomic information can introduce more uncertainty and complexity in care. This study aims to evaluate patients’ DCS score pre or post discussing next generation sequencing (NGS) results with a medical oncologist, and assess factors that correlate with high decision conflict. Methods: Patients diagnosed with incurable/metastatic cancer who underwent molecular characterization with tissue+/- liquid NGS testing were enrolled. Survey instruments included the validated DCS (five subscales: informed, values clarity, support, uncertainty, effective decision), and EQ-5D-5L. DCS was administered pre or post medical oncology consultation that included review of tissue +/- liquid NGS results and treatment options. Higher DCS score correlates with higher perception of uncertainty. Descriptive statistics were used to assess clinical and demographic risk factors. Multivariable logistic regression analysis estimated the correlation between high DCS and clinical factors. Results: 335 DCS surveys were completed by 227 patients: 188 before and 147 after discussing tissue+/- liquid NGS results with a medical oncologist. Baseline characteristics: 56% female, median age 65, ECOG 0-1 58%, median EQ5D VAS score 68, GI/lung/gyne/breast/other 42/32/10/5/11%, white/Asian/other/unknown 66/12/5/17%. Tier 1 variants were identified in 35% of patients. Patients reported decreased decision conflict after consultation. Multivariable logistic regression analysis including sex, age, race and tumor group did not predict for high DCS pre-consultation. MVA post NGS results that also included Tier 1 variants (present / absent) did not predict for high DSC post consultation. Conclusions: Communication regarding genomic-based tumor assessment can positively support patients in decision conflict, and improve their confidence in their treatment choice, regardless of the findings of the report. Low DCS after consultation supports the goal of shared decision making for cancer treatment. Clinical trial information: NCT05057234 . DCS subscale Pre-consultation Post-consultation p value Informed 49.3 37.5 <0.001 Values clarity 45.3 35.5 <0.001 Support 34.4 28.2 0.005 Uncertainty 46.8 36.1 <0.001 Effective decision 40.0 31.4 <0.001 TOTAL 42.9 33.6 <0.001
