Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC).

To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients.

Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer.

We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in TP53 (47.3%), PMS2 (26.3%), MRE11 (26.3%), RB1 (10.5%), BRCA1 (10.5%), PTEN (10.5%) and AR (10.5%); other affected genes included PMS1, KMT2C, BRCA2, PALB2, MUTYH, MEN1, MSH2, CHEK2, NCOR1, PIK3CA, ESR1 and MAP2K4. In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AFtissue ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.

Moral Distress, Organizational Climate, and the Risk of Burnout Among Physician Assistants in Oncology.

PURPOSE: Moral distress (MD) is the result of barriers or constraints that prevent providers from carrying out what they believe to be ethically appropriate care. This study was initiated to explore associations between MD, burnout, and the organizational climate (OC) for oncology physician assistants (PAs). METHODS: A national survey of oncology PAs was conducted to explore the associations between MD, OC, and burnout. The Nurse Practitioner-Primary Care OC Questionnaire was revised for oncology PAs to assess OC for PA practice. MD and burnout were assessed using the Measure of MD-Healthcare Professionals (MMD-HP) and the Maslach Burnout Inventory. RESULTS: One hundred forty-six oncology PAs are included in the analysis. PAs were mostly female (90%), White/Caucasian (84%), married/partnered (78%), and in medical oncology (73%), with mean age 41.0 years. The mean MMD-HP score for oncology PAs was 71.5 and there was no difference in MD scores on the basis of oncology subspecialty, practice setting, practice type, or hours worked per week. PAs currently considering leaving their position because of MD had significantly higher mean scores on the MMD-HP compared with those not considering leaving their position (108.2 v 64.8; P = .001). PAs with burnout also had significantly higher mean scores for MD compared with PAs without burnout (97.6 v 54.3; P < .001). A negative relationship between OC for PA practice and MD was only found for the PA-administration relations subscale, whereas all subscales were negatively associated with burnout. CONCLUSION: This study demonstrates that the risk of professional burnout increases significantly with increasing levels of MD. Additional research exploring the relationship between MD and burnout is needed.

Association of Organizational Context, Collaborative Practice Models, and Burnout Among Physician Assistants in Oncology.

PURPOSE: Despite an increase in the number of physician assistants (PAs) in the oncology workforce, their potential to meet anticipated demand for oncology services may be hindered by high rates of burnout. The aim of this study was to examine the association between organizational context (OC) and burnout among oncology PAs to better understand factors associated with burnout. METHODS: A national survey of oncology PAs was conducted to explore relationships between burnout and the OC in which the PA practiced. The Areas of Worklife Survey (AWS) assessed OC by examining six key workplace qualities (workload, control, reward, community, fairness, and values). Burnout was assessed using the Maslach Burnout Inventory. RESULTS: PAs demonstrating burnout scored significantly lower across all domains of the AWS than those without burnout (P < .001 for each AWS subscale). The median score for each domain of the AWS and burnout (No v Yes) were as follows: workload (3.33 v 2.67), control (3.67 v 3.00), reward (4.00 v 3.67), community (4.00 v 3.67), fairness (3.33 v 2.67), and values (4.00 v 3.33). Multivariable analysis found that mismatches between the PA and their work environment in workload (odds ratio [OR] = 1.99; 95% CI, 1.32 to 3.02; P = .001), reward (OR = 1.89, 95% CI, 1.18 to 3.02; P = .008), and values (OR = 2.25; 95% CI, 1.31 to 3.88; P = .003) were more likely to report burnout. Differences in burnout in the context of workload were not explained by patient volume, practice structure, or professional autonomy. CONCLUSION: Workload, reward, and values were associated with greater odds of burnout, with workload being the most common mismatch in job fit. Sustainable workloads and consistency in rewards (financial, institutional, and social) for oncology PAs should be an employer's focus to help mitigate their risk of burnout.

Changes in Burnout Among Oncology Physician Assistants Between 2015 and 2019.

PURPOSE: Burnout has significant implications for the individual provider, the oncology workforce, and the quality of care for patients with cancer. The primary aim of this study was to explore temporal changes in burnout among physician assistants (PAs) in oncology in 2019 compared with 2015. METHODS: Oncology PAs were surveyed to assess for burnout using the Maslach Burnout Inventory according to the same cross-sectional design of the study performed in 2015. Comparison between oncology PAs in 2015 and 2019 in the prevalence of burnout and personal and professional characteristics was performed. RESULTS: Two hundred thirty-four participants completed the full-length survey. The participants in 2015 and 2019 were similar in age (41.8 v 40.3 years), sex (88.8% v 86.3% female), number of years as a PA in oncology (9.6 v 10), and percentage involved in academic practice (55.2% v 59.2%). There was a significant increase in burnout in 2019 compared with 2015 with 48.7% of PAs reporting at least one symptom of burnout compared with 34.8% (odds ratio for burnout, 2019 v 2015 = 1.92 [95% CI, 1.40 to 2.65], P < 0.001). The odds of burnout remained higher in 2019 compared with 2015 when adjusted for age, sex, relationship status, practice setting, subspecialty, practice type, and hours worked. Factors associated with burnout in both 2015 and 2019 include the percentage of time spent on patient care, collaborative physician relationship, number of hours worked, and satisfaction with compensation. No new factors associated with burnout emerged in 2019 that were not identified in 2015. CONCLUSION: The rate of burnout of oncology PAs has significantly increased. Burnout in oncology PAs is multifactorial, and the increase cannot be easily explained. Additional research is needed to better define the drivers of PA burnout.