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Background: The Advanced Breast Cancer Alliance conducted a nationwide investigation to understand the current situation of the diagnosis and treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) patients. Methods: In 2019, electronic questionnaires including basic information about respondents, characteristics of patients, and the present status of diagnosis and treatment were sent to 495 doctors from 203 medical centers covering 28 provinces. Results: The factors that influenced treatment plans included the disease process, the performance status, and the economic status of patients. Regimens and response to neoadjuvant/adjuvant chemotherapy were important factors in the decision of the first-line treatment. Overall, 54% of doctors retained trastuzumab and replaced chemotherapy drugs in second-line treatment regimens for patients with progression-free survival (PFS) ≥ 6 months in the first-line setting, while 52% of participants chose pyrotinib plus capecitabine for patients with PFS < 6 months. Economic factors played an important role in doctors' decision-making and the varying treatment options for respondents in first-tier, second-tier, and other cities. Conclusions: This large-scale survey regarding the diagnosis and treatment of HER2-positive MBC patients revealed that clinical decisions made by Chinese doctors followed the guidelines, but their choices were constrained by economic factors. [ABSTRACT FROM AUTHOR]

The optimal therapeutic options, adding locoregional therapy (LRT) to systemic therapy (ST) or not, for patients with oligometastatic breast cancer (OMBC) have not been fully elucidated. Hence, we designed a retrospective observational study which enrolled patients with measurable extracranial OMBC having less than 5 metastatic lesions not necessarily in the same organ. We retrospectively reviewed a total of 199 patients diagnosed with extracranial OMBC, including 28 receiving ST followed by LRT (ST to LRT group), 44 receiving LRT followed by ST (LRT to ST group), and 127 receiving ST alone (ST alone group). After a median follow-up of 28.7 months, patients receiving both ST and LRT had a significantly better prognosis than those receiving ST alone: the median progression-free survival (PFS) was 16.3, 14.0, and 9.3 months (P < 0.001) and the median overall survival (OS) was 39.8, 70.5, and 26.7 months (P < 0.001) in the ST to LRT, LRT to ST, and ST alone groups, respectively. Sequence of ST and LRT had no significant impact on survival among patients receiving both. Further exploratory analysis identified ST plus LRT as an independent predictor for longer PFS. In conclusion, we demonstrated that adding LRT to ST was associated with survival benefits for patients with OMBC, and further prospective studies were warranted. [ABSTRACT FROM AUTHOR]

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role in the underlying regulatory mechanism in TNBC are lacking. In this study, we investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the m6A methylated RNA was dramatically decreased in TNBC tissues and cell lines. Functionally, we demonstrated that METTL3 inhibits the proliferation, migration, and invasion ability of TNBC cells. Moreover, we found METTL3 is repressed by miR-34c-3p in TNBC cells. On the mechanism, we found that circMETTL3 could act as a sponge for miR-34c-3p and inhibits cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR-34c-3p target gene METTL3. In conclusion, our study demonstrates the functional importance and regulatory mechanism of METTL3 in suppressing the tumor growth of TNBC. [ABSTRACT FROM AUTHOR]

Lessons Learned: Moxifloxacin plus continuation of the previous treatment of physician's choice shows promising efficacy in patients with metastatic breast cancer.The addition of moxifloxacin shows well‐tolerated toxicities. Background: Recent studies have confirmed bacterial infection as an important contributor in cancer. Elimination of tumor‐associated microbes may lead to a reduction in tumors and improved survival. Moxifloxacin is an orally administrated fourth‐generation quinolone with broad‐spectrum coverage against tumor‐associated bacteria. Methods: In this study, we assessed the efficacy and safety of moxifloxacin in combination with treatment of physician's choice (TPC) in patients with metastatic breast cancer (MBC). In this single‐arm, phase II study, we recruited 30 patients with MBC who had a trend toward disease progression (stable disease [SD] with increased tumor size) during TPC before enrollment at Sun Yat‐sen University Cancer Center between January 1 and July 30, 2018. Eligible patients were given moxifloxacin once daily at a dose of 400 mg from days 1 to 7 of a 28‐day cycle, in addition to continuing to receive the therapy previously selected by their physicians. Tumor response was determined according to RECIST (version 1.1). Progression‐free survival (PFS) was calculated using the Kaplan‐Meier method. Results: The concomitant use of moxifloxacin and previous TPC yielded a median PFS of 6.6 months (95% confidence interval [CI]: 4.0–9.1) and a 1‐year PFS of 25.9% (95% CI: 10.0%–41.9%). Objective responses were achieved in seven (23.3%, 95% CI: 7.3%–39.4%) patients. The clinical benefit rate was 46.7% (95% CI: 27.7%–65.6%). No grade 4 adverse events (AEs) and four grade 3 AEs were observed, none of which were considered to have definite relation to moxifloxacin. Conclusion: The combination of moxifloxacin with previous TPC shows promising efficacy and well‐tolerated toxicities in patients with MBC. [ABSTRACT FROM AUTHOR]

Lessons Learned: Administration of lapatinib with food significantly increased its plasma concentration in Chinese patients with metastatic breast cancer.There were no serious adverse events during the study and no significant differences in lapatinib‐related adverse events between the fasted and fed states. Background: Lapatinib, a small molecular reversible dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth receptor 2 (HER2), was approved for use in combination with capecitabine to treat metastatic HER2‐positive breast cancer. Administration of lapatinib in the fasted state was recommended; however, our preliminary phase II trial data showed that administration of lapatinib with food increased its concentration. Methods: This study was a single‐center, open‐label, and prospective self‐controlled clinical study. Ten Chinese patients with metastatic breast cancer were enrolled from June 2017 to April 2018. They were required to receive lapatinib plus physician's choice of chemotherapy. Patients were required to take lapatinib orally on an empty stomach continually for 10 days, and then take lapatinib with food continually for the next 10 days. Plasma concentration was measured by liquid chromatography on the 9th and 10th day of each state. Results: Area under the concentration‐time curve (AUC) of the fasted state and the fed state was 21.23 ± 8.91 mg*h/L (coefficient of variation (CV)% 42%) and 60.60 ± 16.64 mg*h/L (CV% 27%), respectively. The mean plasma concentration in the fasted state was 0.88 ± 0.39 mg/L (CV% 45%), and that in the fed state was 2.53 ± 0.77 mg/L (CV% 30%). Compared with taking lapatinib on an empty stomach, receiving lapatinib with food significantly increased the plasma concentration of lapatinib (Wilcoxon match‐paired test, p =.005). In addition, there were no serious adverse events during the study or significant difference in lapatinib‐related adverse events between the two states. Conclusion: Our study shows that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug‐related toxicity. We suggest that a larger‐sample‐size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [ABSTRACT FROM AUTHOR]

Background: Approximately 8.3–15.9% of patients with clinical stage I non‐small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. Methods: This is a multicenter retrospective analysis of pathological T1 non‐small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large‐scale Data Analysis Center of Cancer Precision Medicine‐LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. Results: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9–86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). Conclusion: This real‐world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis. [ABSTRACT FROM AUTHOR]