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Safe and noninvasive methods for breast cancer screening with improved accuracy are urgently needed. Volatile organic compounds (VOCs) in biological samples such as breath and blood have been investigated as noninvasive novel markers of cancer. We investigated volatile organic compounds in urine to assess their potential for the detection of breast cancer. One hundred and ten women with biopsy-proven breast cancer and 177 healthy volunteers were enrolled. The subjects were divided into two groups: a training set and an external validation set. Urine samples were collected and analyzed by gas chromatography and mass spectrometry. A predictive model was constructed by multivariate analysis, and the sensitivity and specificity of the model were confirmed using both a training set and an external set with reproducibility tests. The training set included 60 breast cancer patients (age 34–88 years, mean 60.3) and 60 healthy controls (age 34–81 years, mean 58.7). The external validation set included 50 breast cancer patients (age 35–85 years, mean 58.8) and 117 healthy controls (age 18–84 years, mean 51.2). One hundred and ninety-one compounds detected in at least 80% of the samples from the training set were used for further analysis. The predictive model that best-detected breast cancer at various clinical stages was constructed using a combination of two of the compounds, 2-propanol and 2-butanone. The sensitivity and specificity in the training set were 93.3% and 83.3%, respectively. Triplicated reproducibility tests were performed by randomly choosing ten samples from each group, and the results showed a matching rate of 100% for the breast cancer patient group and 90% for the healthy control group. Our prediction model using two VOCs is a useful complement to the current diagnostic tools. Further studies inclusive of benign tumors and non-breast malignancies are warranted.

Colitis is a major immune-related adverse event associated with programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, but the risk of colitis with PD-1 versus PD-L1 inhibitors is not well characterized. We performed a meta-analysis for the incidence of all grade and grade 3–4 colitis with PD-1 inhibitor (nivolumab, pembrolizumab, and cemiplimab) or PD-L1 inhibitor (atezolizumab, avelumab, and durvalumab) monotherapy using a fixed effects model. We also conducted subgroup meta-analyses of non–small cell lung cancer (NSCLC) or urothelial carcinoma (UC) trials, and a network meta-analysis of randomized trials comparing PD-1 or PD-L1 inhibitors with docetaxel for NSCLC. We also analyzed the Food and Drug Administration Adverse Event Reporting System database to estimate the reporting odds ratio of each medication. PD-1 inhibitors were associated with a higher incidence of all grade and grade 3–4 colitis compared with PD-L1 inhibitors in the analysis of all cancer types [1.49% vs. 0.83%, relative risk; 1.80, 95% confidence interval (CI); 1.22–2.67 for all grade colitis, and 0.85% vs. 0.34%, relative risk; 2.52, 95% CI; 1.46–4.37 for grade 3–4 colitis]. The meta-analyses of NSCLC and UC trials, and the network meta-analysis of NSCLC trials were also suggestive of a higher risk of colitis with PD-1 versus PD-L1 inhibitors. The reporting odds ratio of colitis with PD-1 versus PD-L1 inhibitors was 1.80 (95% CI; 1.53–2.14). In this meta-analysis of clinical trials exploring PD-1 and PD-L1 inhibitors in solid tumors, PD-1 inhibitors were associated with a higher risk of colitis.

Background: The best regimen of neo-adjuvant therapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin or pembrolizumab improves the rate of pathologic complete response (pCR) in TNBC. Therefore, we performed a network meta-analysis to define the overall, most effective, neo-adjuvant systemic therapy for TNBC. Methods: We searched for studies comparing different neo-adjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens using the random-effects model. We focused on anthracycline, bevacizumab, pembrolizumab, and platinum salts (Pl). All study regimens contained a taxane. We analyzed the rate of pCR (ypT0/is, N0), and the incidence of febrile neutropenia, grade 3-grade 4 thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared ten different classes of regimens. We found that regimens containing Pl were significantly superior to non-PI-containing regimens for the rate of pCR. Similarly, pembrolizumab-containing regimens were associated with significantly higher pCR rates. Regimens containing bevacizumab significantly increased the rate of pCR as well. However, it was equivocal as to whether the addition of Pl to pembrolizumab-containing regimen increases pCR rates. Adding anthracycline into the regimen did not show an improved rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of febrile neutropenia and grade 3-grade 4 thrombocytopenia. The regimen containing anthracycline plus bevacizumab plus Pl was associated with a higher risk of gastrointestinal adverse events. Conclusions: For TNBC, regimens containing bevacizumab, pembrolizumab, or Pl are most effective in terms of pCR rates, though it is unclear whether combining all these medications has the greatest efficacy. Additionally, the benefit of using anthracycline in the neo-adjuvant therapy regimen for TNBC is not apparent, which may warrant a further head-to-head comparison.