Yufeng Lin

BACKGROUND: To stage axillary lymph nodes in women with early-stage breast cancer, sentinel lymph node biopsy (SLNB), rather than axillary lymph node dissection (ALND), has been employed. Moreover, different tracer methods have various advantages and disadvantages. In recent years, carbon nanoparticle suspensions (CNSs) have been used as lymph node tracers during surgeries for thyroid cancer, gastric cancer, and colorectal cancer. The study retrospectively analyzed the feasibility and accuracy of CNS for sentinel lymph node (SLN) mapping in patients with early breast cancer. METHODS: This single-center, retrospective study included breast cancer patients who underwent SLNB from January 1, 2016, to December 31, 2017, in the Department of Breast Cancer, Guangdong General Hospital. All patients received standard SLNB surgery using a CNS tracer. RESULTS: A total of 332 cases were included in this study. The SLN identification rate was 99.1% (329/332), and the mean number of SLNs was 2.6 (range, 1-6). SLN metastasis was found in 62 (18.8%) cases, of which 90.3% were found to be macrometastases. The sensitivity of SLNB was 95.9% (47/49), with a specificity of 100% (42/42), a positive predictive value of 100% (47/47), a negative predictive value of 95.5% (42/44), and a false-negative rate of 4.1% (2/49). CONCLUSION: The identification and predictive values of a CNS tracer for SLNB were satisfactory.

Chemoresistance is a main cause of colorectal cancer (CRC) treatment failure. We identified that Bacteroides fragilis is enriched in patients with CRC resistant to chemotherapy in two independent cohorts, and its abundance is associated with poor survival. Consistently, administration of B. fragilis to CRC xenografts and Apc Min/+ - and AOM/DSS-induced CRC mice all significantly attenuated the antitumor efficacy of 5-FU and OXA. Mechanistically, B. fragilis colonized colon tumors and mediated its effect via its surface protein SusD/RagB binding to the Notch1 receptor in CRC cells, leading to activation of the Notch1 signaling pathway and the induction of epithelial-to-mesenchymal transition (EMT)/stemness to suppress chemotherapy-induced apoptosis. Either deletion of SusD/RagB or blockade of Notch1 signaling abrogated B. fragilis -mediated chemoresistance. Finally, B. fragilis -targeting phage VA7 selectively suppressed B. fragilis and restored chemosensitivity in preclinical CRC mouse models. Our findings have offered insights into the potential of precise gut microbiota manipulation for the clinical management of CRC. • B. fragilis is enriched in non-responders of patients with CRC to chemotherapy • B. fragilis compromises 5-FU/OXA efficacy in CRC cells and in mouse models • B. fragilis surface SusD/RagB binds to host receptor Notch1, inducing chemoresistance • Phage VA7 eliminates B. fragilis and restores chemosensitivity of CRC in mice Ding et al. identify Bacteroides fragilis as a bacterial pathogen that promotes colorectal cancer (CRC) chemoresistance by activating host Notch1 signaling through its surface protein SusD/RagB. Targeting B. fragilis with a phage therapy restores chemotherapy sensitivity in CRC mouse models.

BACKGROUND: Tumor location in the breast varies, with the highest frequency in the upper outer quadrant and lowest frequency in the lower inner quadrant. Nevertheless, tumors in the central and nipple portion (TCNP) are poorly studied types of breast cancer; therefore, we aimed to clarify the clinicopathological characteristics and prognostic features of TCNP. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identifed 105,037 patients diagnosed with tumor in the breast peripheral quadrant (TBPQ) (n=97,046) or TCNP (n=7,991). The chi-squared test was used to compare categorical variables across TCNP and TBPQ. Cox proportional hazard models with hazard ratios were applied to estimate the factors associated with prognosis. RESULTS: The median follow-up was over 43 months. Compared with TBPQ, TCNP patients were signifcantly older (age ≥66 years: 40.4% vs 34.1%, P<0.001), with larger tumor sizes (>20 mm size: 46.9% vs 37.3%, P<0.001), higher proportions of TNM stage II-III (18.6% vs 9.9%, P<0.001), and more mastectomies (58.1% vs 37.8%, P<0.001). The breast cancer-specifc survival (BCSS)/overall survival (OS) rate was signifcantly worse for TCNP than for TBPQ. Multivariate Cox analysis showed a higher hazard ratios for TCNP over TBPQ (BCSS: hazard ratios =1.160, P=0.005, 95% CI: 1.046-1.287; OS: hazard ratios =1.301, P<0.001, 95% CI: 1.211-1.398). A subgroup analysis revealed inferior outcomes for TCNP in TNM stage II-III and breast subtype subgroup. Multivariate logistic regression indicated that TCNP was an independent contributing factor to LN metastasis. CONCLUSIONS: TCNP was associated with older age, larger tumor size, higher TNM stage, and lymph node metastasis. Compared with TBPQ, TCNP had adverse impacts on BCSS and OS.

Microbial alterations in different tumor locations of colorectal cancer (CRC) remain unclear. Here, 1,375 fecal metagenomes from six in-house and published datasets were analyzed, including 128 right-sided CRC (rCRC), 168 left-sided CRC (lCRC), 250 rectal cancer (RC), and 829 controls. Firmicutes progressively increase from rCRC, lCRC, to RC, in contrast to the gradual decrease of Bacteroidetes. Tumor location-associated fecal microbes are identified, including Veillonella parvula for rCRC, Streptococcus angionosus for lCRC, and Peptostreptococcus anaerobius for RC, while Fusobacterium nucleatum is enriched in all tumor locations. Tumor location-associated bacteria correlate with patient survival. Clinically, we establish a microbial biomarker panel for each tumor location that accurately diagnoses rCRC (area under the receiver operating characteristic curve [AUC] = 91.59%), lCRC (AUC = 91.69%), or RC (AUC = 90.53%) from controls. Tumor location-specific biomarkers also have higher diagnostic accuracy (AUC = 91.38%) than location-non-specific biomarkers (AUC = 82.92%). Overall, we characterize fecal microbes associated with different CRC tumor locations, highlighting that tumor location should be considered in non-invasive diagnosis.

Purpose: Tau is a microtubule-associated protein that can be found in both normal and abnormal breast cells. Whether the expression of Tau protein can predict the response to neoadjuvant chemotherapy (NACT) is still unclear. In this study, we assessed the role of Tau protein expression in predicting a pathological complete response (pCR) to NACT for different subtypes of breast cancer. Methods: Four hundred and sixty-eight eligible patients were retrospectively recruited in our study. The relationship between clinicopathologic factors, including Tau protein expression, and pCR in different subtypes was evaluated using logistic regression analysis. Correlation between Tau and disease-free survival (DFS) and overall survival (OS) was performed using Kaplan-Meier analysis. Results: The expression of Tau protein was negatively correlated with pCR, especially in triple-negative breast cancer (TNBC). No significant difference was observed in the luminal human epidermal growth factor receptor-2 (HER2)-negative subtype and HER2-positive subtype. Patients with pCR were associated with better DFS and OS (p < 0.05). However, Tau protein expression had no association with either DFS or OS (p > 0.05). Conclusion: Tau protein expression can predict pCR before NACT in TNBC, but there was no correlation between Tau expression and DFS or OS.