Ethnic Differences in Germline Genetic Testing For Breast Cancer

Introduction: Ethnic variations in uptake of genetic testing and differences in findings of germline mutations within ethnic groups, are not well understood. The goal of this research is to assess for any such differences or similarities within a genetic counseling and testing program at an urban Cancer Center. Methods: This is a non-comparative, descriptive epidemiology study assessing individuals with a diagnosis of breast cancer undergoing genetic counseling at the TJUH Sidney Kimmel Cancer Center in Philadelphia between 2014 and 2019. Data were compiled onto Research Electronic Data Capture (REDCAP) and analyzed statistically. Results: Patients with Breast Cancer (n=1075) were included in the analysis, 807 of whom had genetic testing conducted. In total, 81 Caucasians had pathogenic/likely pathogenic mutations (13%) and 16% had VUS. African Americans had the highest prevalence of VUS (32%) and 16 pathogenic/likely pathogenic mutations (13%). Asians (n=44) had no pathogenic but 2 likely pathogenic mutations (6%), and 3 VUS (9%). Comparatively, no statistically significant differences were observed. Asians presented for genetic counseling younger (mean age 49) than African Americans (mean age 54) and Caucasians (mean age 58) (p\u3c0.001). Caucasians were more likely to undergo genetic testing (89%) than African Americans (78%) and Asians (79%) (p\u3c0.002). Discussion: These results point toward ethnic differences in utilization and followthrough with genetic testing, as well as variations in genetic mutations. The high prevalence of VUS mutations in African Americans and few mutations in Asians suggests that the mutational spectrum in these populations is not well understood and warrants further study

Success of Preoperative Radiotherapy in Inflammatory Breast Cancer with Inadequate Response to Taxane-Based Chemotherapies

Inflammatory breast cancer is a locally-aggressive and highly malignant cancer which often carries a poor prognosis for afflicted patients. Multi-modality treatment is often required, and taxane-based chemotherapy has shown improved outcomes and allowed for the pursuit of mastectomies, which are critical to disease control. Inadequate response to taxane-based chemotherapy indicates aggressive disease, and the role of preoperative radiotherapy for treatment in this patient group and its effects on patient outcomes and toxicity has not been studied. This study evaluates the effectiveness of preoperative radiotherapy on this patient group. Inflammatory breast cancer patients between 2012-2018 who were not deemed appropriate for resection following taxane-based chemotherapy leading to their referral for preoperative radiotherapy were identified. Patient, disease, and pre-surgical treatment characteristics were collected. A statistical analysis of surgical outcomes with regards to conversion to resectability, surgical margins, treatment response, complication rates, and locoregional recurrence was performed. 9 patients received neoadjuvant radiation following their inadequate response to taxane-based chemotherapy. 8 of 9 patients converted to resectable disease, 100% of which achieved R0 mastectomy. Median residual primary disease was 1cm, with a grade 1 toxicity being noted in 1 patient which resolved with conservative management. A single low cervical recurrence was observed 4 years after mastectomy. Based on the results of this study, preoperative radiation should be considered in inflammatory breast cancer patients who do not demonstrate adequate response to taxane-based chemotherapy. Use of preoperative radiotherapy in this patient group may lead to the improvement of patient outcomes and a decrease in treatment toxicity

Genomic Aberrations in Circulating Tumor DNAs from Palbociclib-Treated Metastatic Breast Cancer Patients Reveal a Novel Resistance Mechanism.

Previously undescribed molecular mechanisms of resistance will emerge with the increased use of cyclin-dependent kinase 4/6 inhibitors in clinical settings. To identify genomic aberrations in circulating tumor DNA associated with treatment resistance in palbociclib-treated metastatic breast cancer (MBC) patients, we collected 35 pre- and post-treatment blood samples from 16 patients with estrogen receptor-positive (E