tumor volume was calculated using the equation: volume = (length × width 2) × π/6. Additive and synergistic effects were calculated using the FTV method as previously described (59, 60). Study approval. The protocols used in this study were approved by the IACUC of the University of Michigan. Statistics. Statistical analyses were performed using GraphPad Prism 7.0 (GraphPad Software). A log-rank (Mantel-Cox) test was used for survival curve analyses. One-way ANOVA was performed for BC subtype analysis. A 2-sided Student's t test and 1-way ANOVA with Dunnett's multiple comparisons test were used for in vitro statistical analyses. A 1-way ANOVA with Dunnett's multiple comparisons test and a log-rank (Mantel-Cox) test were used for in vivo analyses. A P value of 0.05 or less was considered statistically significant.

Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), with local control rates of 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there is a clear need for intensification of local therapy, including radiation. Inhibition of the DNA repair protein PARP1 has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with BRCA mutations; however, PARP1 inhibition (PARPi) may lead to the radiosensitization of aggressive tumor types. Thus, this study investigates inhibition of PARP1 as a novel and promising radiosensitization strategy in IBC. In multiple existing IBC models (SUM-149, SUM-190, MDA-IBC-3), PARPi (AZD2281-olaparib and ABT-888-veliparib) had limited single-agent efficacy (IC 50 > 10 mmol/L) in proliferation assays. Despite limited single-agent efficacy, submicromolar concentrations of AZD2281 in combination with RT led to significant radiosensitization (rER 1.12-1.76). This effect was partially dependent on BRCA1 mutational status. Radiosensitization was due, at least in part, to delayed resolution of double strand DNA breaks as measured by multiple assays. Using a SUM-190 xenograft model in vivo, the combination of PARPi and RT significantly delays tumor doubling and tripling times compared with PARPi or RT alone with limited toxicity. This study demonstrates that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT AE PARPi in women with IBC (SWOG 1706, NCT03598257).

Michmerhuizen et al. Seviteronel Radiosensitizes AR+ TNBC RT, suggesting that seviteronel may have a different mechanism of radiosensitization compared to other AR inhibitors. Enzalutamide and seviteronel treatment also had different effects on AR and AR target genes as measured by immunoblot and qPCR. These results implicate AR as a mediator of radioresistance in AR+ TNBC models and support the use of seviteronel as a radiosensitizing agent in AR+ TNBC.

BACKGROUND:The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area-level socioeconomic status (SES) among women diagnosed with stage IIIB-IV BC in Georgia. METHODS: Using the Georgia Cancer Registry, 3084 patients with stage IIIB-IV primary BC (2013-2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non-Hispanic Black (NHB) versus non-Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low-versus high-SES neighborhoods by tumor, treatment, and patient characteristics. The mediating effects of specific characteristics on the association between race and BC mortality were estimated. RESULTS: Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. The authors observed mortality disparities by race (

◥Non-Hodgkin lymphoma comprises a heterogeneous group of hematologic malignancies, with about 60 subtypes that arise via various pathogenetic mechanisms. Although establishing etiology for specific NHL subtypes has been historically difficult given their relative rarity, environmental exposures have been repeatedly implicated as risk factors across many subtypes. Large-scale epidemiologic investigations have pinpointed chemical exposures in particular, but causality has not been established, and the exact biologic mechanisms underpinning these associations are unclear. Here we review chemical exposures that have been associated with development of NHL subtypes and discuss their biologic plausibility based on current research.