Cell-free DNA concentration as a biomarker of response and recurrence in HER2-negative breast cancer receiving neoadjuvant chemotherapy.

PURPOSE: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients. EXPERIMENTAL DESIGN: 145 hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) patients with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined. RESULTS: In TNBC, we observed a modest negative correlation between cfDNA concentration 3 weeks after treatment initiation and RCB, but none of the other timepoints showed significant correlation. In contrast, ctDNA was significantly positively correlated with RCB at all timepoints (all R>0.3 and p<0.05). In the HR-positive/HER2-negative group, cfDNA concentration did not associate with response to NAC, but survival analysis showed that high cfDNA-shedders at pretreatment had a significantly worse DRFS than low shedders (hazard ratio 2.12, p=0.037). In TNBC, the difference in survival between high vs. low cfDNA-shedders at all timepoints was not statistically significant. In contrast, as previously reported, ctDNA at all timepoints was significantly correlated with DRFS in both subtypes. CONCLUSIONS: In TNBC, cfDNA concentrations during therapy were not strongly correlated with response or prognosis. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA.

Optimization of soaking conditions (temperature and time) on physicochemical properties of selected parboiled rice varieties grown in Eastern Ethiopia.

This study aimed to optimize soaking temperature and time for better physicochemical properties of parboiled rice varieties grown in Eastern Ethiopia. Two brown rice varieties (NERICA-4 and NERICA-6) were collected from the Somali Regional Agricultural and Pastoral Research Center in Gode. The experiment was designed to aid the design expert software using box-behnken experimental design of response surface methodology to optimize the effects of soaking temperature (60-70°C) and soaking time (4-6 h). Relevant physical and chemical composition properties of the parboiled rice varieties were investigated using standard methods. Numerical optimization of the responses was performed using design expert software. The results showed that soaking time and temperature significantly (p < .05) influenced the physicochemical quality of studied brown rice varieties. The optimal soaking temperature and time were 65°C and 6 h, respectively, for NERICA-4. Under these conditions, the optimum response variables obtained were 375.37 N, 52 min, 12.3%, 1.24%, 13.86%, 2.17%, 3.2942%, 67.1171%, 343.5 kcal/100 g, 274.72 mg/100 g, 318.35 mg/100 g, and 268.31 mg/100 g for hardness, cooking time, moisture, ash, protein, fat, fiber, carbohydrate, energy, magnesium, and potassium and phosphorous content, respectively. However, 65°C and 5 h were optimum soaking temperatures and time for NERICA-6, giving hardness, cooking time, moisture, ash, protein, fat, fiber, carbohydrate, energy content, magnesium, potassium, and phosphorous of 375.18 N, 52 min, 12.2%, 1.4%, 11.54%, 2.29%, 2.89%, 69.6%, 345.42 kcal/100 g, 156 mg/100 g, 105.9 mg/100 g and 136.9 mg/100 g, respectively. The findings showed that rice varieties, in particular NARICA 4, were processed under optimal parboiling conditions in the study setting for better physical properties, proximate composition, and mineral content.

Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy.

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival in both subtypes. Conversely, ctDNA negativity after NAC correlates with improved outcomes, even in patients with extensive residual cancer. Pretreatment tumor mRNA profiling reveals associations between ctDNA shedding and cell cycle and immune-associated signaling. On the basis of these findings, the I-SPY2 trial will prospectively test ctDNA for utility in redirecting therapy to improve response and prognosis.