Background: Epithelial–mesenchymal transition (EMT) is implicated in the metastatic process and presents a challenge to epithelial cell adhesion molecule‐based detection of circulating tumor cells (CTCs), which have been demonstrated to be a prognostic indicator in metastatic breast cancer. Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression, no standard recommendations have been established for clinical practice. This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients. Methods: We enrolled 108 human epidermal growth factor receptor 2‐negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) in peripheral blood samples. Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1‐year progression‐free survival (PFS) rate were conducted to determine the optimal cut‐off values, and Kaplan–Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut‐off values of both total CTC count and the proportion of mesenchymal CTCs in combination. Results: For predicting the 1‐year PFS rate, the optimal cut‐off value of total CTC count was 9.5 (Area under the curve [AUC] = 0.538, 95% confidence interval [CI] = 0.418–0.657), and that of the proportion of mesenchymal CTCs was 10.7% (AUC = 0.581, 95% CI = 0.463–0.699). We used the two cut‐off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%. Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria (6.2 vs. 9.9 months, P =0.010). A nomogram was constructed based on the criteria and significant clinicopathological characteristics with a C‐index of 0.613 ( P = 0.010). Conclusions: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer. Trial registration ClinicalTrials.gov . NCT01917279. Registered on 19 July 2013, https://clinicaltrials.gov/ct2/show/NCT01917279?term=NCT01917279&rank=1 .

Background: Human epidermal growth factor 2 (HER2)-low breast cancer, which is defined as HER2 1+ or 2+ in immunohistochemistry without gene amplification, accounts for a considerable part of all breast cancers. However, it remains controversial whether HER2-low breast cancer is a distinct entity. Our aim was to compare the clinicopathological features and survival outcomes between HER2-zero and HER2-low early breast cancer.Methods: The study was a retrospective analysis that enrolled 1,039 patients with available HER2 expression data in a single institute from 2013 to 2014, of whom 262 HER2-positive patients were excluded from the subsequent analysis. The remaining patients were divided into HER2-zero and HER2-low groups. Each group was further categorized into a hormone receptor (HR)-positive and an HR-negative subgroup. Clinicopathological characteristics were collected and compared between HER2-zero and HER2-low groups. The primary endpoint was disease-free survival (DFS) and overall survival (OS), which were analyzed using the Kaplan–Meier method with log-rank test, landmark analysis, and Cox proportional hazards model.Results: A total of 777 non-HER2-positive patients were included in this analysis, of whom 126, 552, 53, and 46 patients were HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, and HR-negative/HER2-low, respectively. No significant difference in DFS and OS was detected between the HER2-zero group and the HER2-low group when paired by HR status. Landmark analysis with a time point set at 5 years indicated that HR-positive/HER2-low patients had a better DFS compared with HR-positive/HER2-zero patients after 5 years (p = 0.0047). HER2-low status was an independent prognostic factor for DFS after 5 years [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13–0.75, p = 0.01].Conclusion: The clinicopathological characteristics and prognosis of HER2-zero and HER2-low breast cancer were similar regardless of HR status. Patients with HR-positive/HER2-low tumors tended to have a better DFS than their HR-positive/HER2-zero counterparts after 5 years.

To explore the clinicopathological features and prognosis of breast cancer with special histological types. The information of breast cancer patients was obtained from the Surveillance, Epidemiology, and End Results (SEER) database (2010–2016). Comparative analyses were performed to explore the difference in clinicopathological characteristics and propensity score matching (PSM) was used to weaken the effects from clinical profiles. Survival analysis was conducted to investigate the prognostic effects from histological types, and the prognostic factors of this group of patients were identified with the univariate COX proportional model. A total of 242863 breast cancer patients were eligible, of which 230213 individuals were ductal breast cancer (IDC) and 12650 individuals were special breast lesions, respectively. Comparatively, special breast cancer had a lower histological grade, a smaller tumor size, a lower proportion of nodal involvement and distant metastasis, in addition to a higher proportion of triple-negative subtype. The overall prognosis of special histological breast cancer was comparable to IDC, while the survival of HER2 enriched breast cancer was in favor of special breast cancer. With the PSM performance, the prognosis exhibited an inferior profile in the metaplastic breast cancer and was significantly favorable to apocrine, medullary, micropapillary, and papillary breast cancer. This study revealed that the special histological breast cancer presented distinct clinicopathological characteristics and great heterogeneity in the prognosis among diverse histological subtypes.

In our phase Ib trial (ClinialTrials.gov Identifier: NCT03855358), benmelstobart (TQB2450), a novel humanized IgG1 antibody against PD-L1, plus antiangiogenic multikinase inhibitor, anlotinib, demonstrated promising antitumor activities in pretreated triple negative breast cancer (TNBC) patients. We conducted explorative analyses of genomic biomarkers to explore the associations with treatment response and survival outcomes. Targeted next generation sequencing (NGS) was undertaken toward circulating tumor DNA (ctDNA) collected from peripheral blood samples prior to the start of treatment and after disease progression. A total of 31 patients received targeted NGS and functional driver mutations in 29 patients were analyzed. The most frequent mutations were TP53 (72%), MLL3 (28%), and PIK3CA (17%). At a blood-based tumor mutational burden (bTMB) cutoff of 6.7 mutations per megabase, patients with low bTMB showed better response to anlotinib plus TQB2450 (50% vs. 7%, P = 0.015) and gained greater PFS benefits (7.3 vs. 4.1 months, P = 0.012) than those with high bTMB. At a maximum somatic allele frequency (MSAF) cutoff of 10%, a low MSAF indicated a better objective response (43% vs. 20%) as well as a significantly longer median PFS (7.9 vs. 2.7 months, P < 0.001). Patients with both low MSAF and low bTMB showed a notably better objective response to anlotinib plus TQB2450 (70% vs. 11%, P < 0.001) and a significantly longer median PFS (11.0 vs. 2.9 months, P < 0.001) than patients with other scenarios. Our findings support future studes and validation of MSAF and the combined bTMB-MSAF classification as predictive biomarkers of immune checkpoint inhibitor-based regimens in advanced TNBC patients.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC).Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites.Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07).Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

To investigate the performance of methylated SEPT9 (mSEPT9) in assessing the surgical therapeutic effect and prognosis of colorectal cancer (CRC). Blood samples before surgery and 1 and 7 days after surgery were obtained from 120 CRC patients, and mSEPT9 and carcinoembryonic antigen (CEA) assays were performed. The mean plasma mSEPT9 level showed 57.6-times and 131.1-times decrease 1 day and 7 days after surgery, respectively. In contrast, mean CEA levels showed 2.51-and 2.70-times decrease 1 and 7 days after surgery. 86.7% of patients can be assessed by mSEPT9 while 44.2% can be assessed by CEA. Positive mSEPT9 detection before surgery correlated with higher risk of death after surgery. mSEPT9 is effective for CRC postsurgical assessment and prognosis prediction.