Citations

1514 Background: The prevalence of germline mutations in non-white patients with breast cancer and the germline genetic drivers of breast cancer risk in non-white populations are largely unknown. Methods: The study population included 77,900 women with breast cancer (Non-Hispanic white: 57,003; Black: 6,722; Asian: 4,183; Hispanic: 5,194; Ashkenazi-Jewish: 4,798) who underwent germline multigene panel testing of cancer predisposition genes from March 2012 to December 2016. The prevalence of predisposition gene mutations in racial and ethnic populations relative to non-Hispanic Whites was assessed while accounting for age at diagnosis of breast cancer, family history of breast and ovarian cancer, and estrogen receptor status of breast tumors. Associations between mutations in each gene and breast cancer risk were evaluated using reference controls. Results: The overall frequency of pathogenic mutations in known breast cancer predisposition genes was 9.1% for non-Hispanic Whites, 9.8% for African Americans, 10.2% for Hispanics, 7.6% for Ashkenazi-Jewish, and 7.5% for Asians. BRCA1 mutations were enriched (p < 0.05) and CHEK2 mutations were under-represented in all racial and ethnic populations relative to non-Hispanic Whites. BRCA2 and BARD1 mutations were enriched in African Americans and Hispanics relative to non-Hispanic Whites, whereas PALB2 and RAD51C mutations were enriched in Hispanics. Among genes with mutation counts large enough for assessment, mutations in BARD1, BRCA1, BRCA2, PALB2 and TP53 were significantly associated with clinically relevant increased risks (odds ratio (OR) > 2) of breast cancer across all ethnicities and races. Rates of variants of uncertain significance were highest among Asians (29%), followed by blacks (27%), Hispanics (21%), non-Hispanic whites (16%) and Ashkenazi-Jews (14%). Conclusions: While there is some similarity across ethnic groups, substantial heterogeneity exists in the prevalence of mutations in breast cancer predisposition genes across major racial and ethnic groups in the US population. These findings contribute to our understanding of breast cancer risk and have significant implications for genetic testing, screening, and management of patients with an inherited predisposition to breast cancer, with a need for continued analysis with increased cohort size in ethnic minority groups.

Objective: The purpose of this study is to evaluate diffusion weighted magnetic rsonance imaging (MRI) acquisitions in delineating posterior extent of breast tumors and in predicting chest wall invasion prior to treatment. To our knowledge, there has not been any literature specifically evaluating the utility of diffusion-weighted acquisitions in chest wall invasion of breast tumors. Materials and Methods: A retrospective review of our breast imaging database for keywords “chest wall invasion” and “breast MRI” was performed over the last 14 years. Diffusion sequences, T1 sequences (pre and post contrast), and T2 sequences were evaluated. Apparent diffusion coefficient (ADC) values in tumor and chest wall were assessed. Imaging findings were correlated with surgical pathology. Results: 23 patients met inclusion criteria. All 23 had loss of fat plane on T2 sequences. 22/23 had loss of fat plane on postcontrast T1 sequences. Pectoralis muscle enhancement was present in 19/23 (83%) tumors and chest wall enhancement was present 9/23 (39%) tumors. Qualitative restricted diffusion within the pectoralis muscle was present in 18/23 (71%) tumors and in the chest wall was present in 8/23 (35%) tumors. Mean ADC values were 1.15 s/mm2 in the tumor and 1.29 s/mm2 in the chest wall. Sensitivity, specificity, positive predictive value and negative predictive value were 100%, 36%, 63%, and 100% for chest wall enhancement respectively and 69%, 36%, 61%, and 80% for chest wall diffusion-weighted imaging restriction respectively. Conclusion: Diffusion weighted sequences can be helpful in characterizing chest wall invasion of breast tumors.

Background The first year of military service in the United States Air Force (USAF) is a high-risk time for tobacco use. Previous studies have demonstrated the effectiveness of a tobacco ban during Basic Military Training (BMT). However, no studies have examined the effect of increasing the protracted ban for an additional 4 weeks. Understanding the patterns of initiation and reinitiation following the protracted ban will inform future intervention and policy efforts. Methods The current study examines patterns of cigarette smoking among a sample of 2188 USAF personnel at baseline and after their first year of service. Results One year after BMT, we observed that 65.0% of USAF enlistees remained never smokers, 9.6% remained abstinence from cigarettes, 9.3% initiated cigarette smoking, and 16.1% reinitiated cigarette smoking. Despite the extended tobacco ban in BMT and Technical Training, 12.6% of individual who never smoked initiated cigarette smoking and 62.6% of individuals who formerly smoked reinitiated. Over half (54.2%) of Airmen who reported smoking cigarettes at follow-up reported initiating or reinitiating during Technical Training. Conclusions Our findings indicate that although the increased ban prevents additional individuals who smoked cigarettes prior to joining the Air Force from reinitiating, it has no effect on initiation among individuals who report never using prior to military service. Additional research is needed to understand what may be leading to these high rates of initiation and reinitiation in Technical Training following the ban.

TPS475 Background: The prognosis of pancreas adenocarcinoma (PCA) remains poor. A chemotherapy backbone is the current standard of care in PCA. The choice of a chemotherapeutic backbone may impact the efficacy of anti-angiogenic therapy in PCA. Ramucirumab has increased activity with fluoropyrimidines (5FU) because 5FU increases VEGF expression. Methods: This is a double-blind, placebo controlled Phase II study. Subjects will receive either Ramucirumab or a placebo followed by mFOLFIRINOX every two weeks of a 28 day cycle until progression or discontinuation for other reasons. The primary endpoint of this clinical trial is nine month PFS defined as the time from enrollment to the time of progression or death. Among the key inclusion criteria, subjects must have recurrent or metastatic pancreas adenocarcinoma (PCA) with no prior first-line systemic treatment, ECOG PS 0-1, adequate organ function, no DVT, PE or other thromboembolism within three months of randomization. Total number of patient enrolled as of September 19, 2018 is 48 of 85 at eight sites; 27 male (56%), 42 Caucasians (87.5%), three African American (6.2%), one Asian (2%). Median age is 63 (40 - 76). Majority of patients (41) had de novo metastatic disease and six with recurrent disease after surgery. Regimen has been tolerated well with no unanticipated events. Clinical trial information: NCT02581215.