Identification of metabolic pathways contributing to ER+ breast cancer disparities using a machine-learning pipeline.

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities.

Breast Imaging Second Opinion Consultation: A Single Institution's Process of Improvement and Reform.

OBJECTIVE: To review a single institution's second opinion breast imaging process, data tracking, and metrics before and after implementing quality improvement changes and the effect on report turnaround time. METHODS: This Institutional Review Board approved retrospective quality improvement project was performed at a tertiary-care academic medical center and included patients 18 years or older who submitted their outside facility imaging for reinterpretation (any combination of mammography, breast ultrasonography, and/or magnetic resonance imaging performed within the last six months) with finalized second opinion reports between June 1, 2016, and July 17, 2017. Significant intradepartmental changes were implemented March 2017 with the goal to improve second opinion report turnaround time. Key metrics from 399 studies were analyzed before and after implemented changes. Two-sided Fisher's exact test was used to assess the significance of results. RESULTS: After department interventions, the percentage of outside reports available at the time of surgical consultation improved from 82% (213/259) to 91% (127/140), an 11% improvement (P < 0.05). The average number of days from initial second opinion consultation to the availability of final report improved from 10.2 days to 9 days, a 12% improvement. Prior to the changes, the number of days it took a radiologist to complete a report varied from 1 to 4 days, but afterwards was consistently 1 day or less. CONCLUSION: Implementation of second opinion intradepartmental changes demonstrated a significant improvement in report turnaround time and the number of finalized reports available at the time of surgical consultation. An efficient second opinion process is crucial to a breast imaging center, as it ultimately expedites patient surgical and oncological care.

Targeted Melanoma Screening: Risk Self-Assessment and Skin Self-Examination Education Delivered During Mammography of Women.

BACKGROUND: Melanoma, which is the sixth most common cancer in women, is visible on the surface of the skin; therefore, self-screening (skin self-examination [SSE]) may be beneficial. METHODS: A convenience sample of women undergoing mammography was sequentially assigned by week into this two-arm targeted melanoma screening intervention. Both groups saw an informational poster and received a brochure promoting risk self-identification and SSE education. One group received an additional 1-week SSE reminder. Participants completed baseline and 1- and 3-month follow-up surveys assessing SSE performance, identifying a concerning mole, scheduling a dermatology appointment, and anxiety due to the program. Performance of SSE between groups was compared using χ2 analysis. The electronic medical record was reviewed for diagnosis of concerning moles. RESULTS: At 1 month, 384 of 420 (91.4% retention) women completed the survey. Of those, 311 (80.9%) performed SSE. Of those who performed SSE, 54 (14%) found a concerning mole at either 1 or 3 months. At 3 months, 346 (82.4% retention) women completed the survey. The number of women who performed SSE did not differ between groups at 1 month (χ2 = 1.64, P = .17) or 3 months (χ2 = 1.58, P = .12). Seven melanomas were found among 34 women who identified a concerning mole; examination of 4.8 women yielded one melanoma. Anxiety was low with a median score of 9.5 (range = 0-42.9). CONCLUSIONS: Introducing melanoma risks and SSE education during mammography was feasible and did not demonstrate harms; thus, there is an opportunity to reach a large, at-risk population with limited burden for the participant and clinics.