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The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n= 353; experimental arm) versus placebo and nab-P (n= 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470–0.906, P= 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414–0.914, P= 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579.

In this study, we aimed to explore the safety and vaccination coverage data of Chinese patients with breast cancer receiving coronavirus disease 2019 (COVID-19) vaccination. The patients were recruited from 41 hospitals across 20 Chinese provinces. The vaccination coverage was approximately 22.4%, and the frequency of total adverse events was 13.3% after the first dose and 9.9% after the second dose. The most frequent adverse reaction within 14 days of the first dose was local pain (5.7%). Unvaccinated patients were very likely to reject the vaccine rather than be hesitant in patients with old age (odds ratio [OR], 1.238; 95% confidence interval [CI], 1.101–1.391), chronic disease history (OR, 1.189; 95% CI, 1.057–1.337), and cancer relapse (OR, 1.398; 95% CI, 1.233–1.585). Of the unvaccinated patients with breast cancer, 54.1% opted to receive COVID-19 vaccines if more data were available. Considering the safety but low vaccination coverage for breast cancer, increased positive attitudes and acceptance toward COVID-19 vaccines are important.

ABSTRACTThyroid cancer (TC) often manifests in the form of a painless cervical mass or nodule and continues to increase in incidence. Currently, much less is known about its pathogenesis in TC cells. This study sought to figure out what role the circular RNA (circRNA) ZNF609/miR-514a-5p might play in TC development and metastasis. In this study, the detection of circ-ZNF609 and miR-514a-5p expressions was carried out by qRT-PCR in TC cell lines. Cell proliferation assessment is employed by cell counting kit-8 (CCK-8) assay, colony formation, Western blot and immunofluorescence. Cell invasion and migration measurement were conducted applying wound healing and transwell. The relationship between circ-ZNF609 and miR-514a-5p was subjected to prediction with bioinformatics analysis and validated with the aid of luciferase reporter assay. Furthermore, xenograft animal experiment was adopted to confirm the role of circ-ZNF609/miR-514a-5p in TC in vivo. The data indicated that circ-ZNF609 was highly expressed, while miR-514a-5p was downregulated in TC cells. Circ-ZNF609 knockdown prevented the malignant biological behaviors of TPC-1 and IHH-4 cells. Besides, circ-ZNF609 sponged miR-514a-5p and miR-514a-5p knockdown reversed the suppressed impacts of circ-ZNF609 knockdown on TC cell malignant biological behaviors. In addition, the silence of circ-ZNF6091 significantly repressed, whereas miR-514a-5p silencing promoted TC tumorigenesis in vivo. The findings highlighted the importance of circ-ZNF609 function in facilitating TC cell development and metastasis in vitroand in vivovia binding to miR-514a-5p.

Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient’s endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.

Objective To investigate the role of promoter and pre-rRNA antisense (PAPAS) long noncoding (Lnc) RNA in cancer biology.Methods Tumour and tumour-adjacent healthy tissue biopsies from patients with triple-negative breast cancer (TNBC), and plasma samples from these patients plus healthy controls, were assessed for PAPAS and microRNA (miR)-34a. Effects of PAPAS and miR-34a overexpression were also investigated in vitro.Results PAPAS was upregulated in tumour tissues of patients with TNBC versus tumour-adjacent healthy tissues. Plasma PAPAS levels were also upregulated in patients with TNBC versus healthy controls. Levels of PAPAS in tumour tissue was significantly positively correlated with PAPAS levels in plasma from patients with TNBC. MiR-34a was downregulated in tumour tissues versus adjacent healthy tissues, and was significantly correlated with PAPAS in tumour tissues. PAPAS overexpression in vitrowas associated with miR-34a inhibition, while miR-34a failed to significantly affect PAPAS levels. PAPAS overexpression promoted in vitromigration and invasion of TNBC cells, while miR-34a overexpression was inhibitory. MiR-34a overexpression decreased the enhanced cell migration and invasion associated with PAPAS overexpression. PAPAS overexpression showed no significant effects on cancer-cell proliferation.Conclusion LncRNA PAPAS may promote TNBC by downregulating miR-34a.

ObjectiveTo assess the efficacy and safety of pyrotinib (an irreversible pan-HER (human epidermal growth factor receptor) inhibitor), trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel for untreated HER2 positive metastatic breast cancer.DesignRandomised, double blind, placebo controlled, multicentre, phase 3 trial.Setting40 centres in China between 6 May 2019 and 17 January 2022.Participants590 female patients (median age 52 (interquartile range 46-58) years) with untreated HER2 positive metastatic breast cancer.InterventionsEligible patients were randomised 1:1 to receive either oral pyrotinib (400 mg once daily) or placebo, both combined with intravenous trastuzumab (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21 day cycle. Randomisation was stratified by treatment history of trastuzumab in the (neo)adjuvant setting and hormone receptor status. Patients, investigators, and the sponsor’s study team were masked to treatment assignment.Main outcome measuresThe primary endpoint was progression-free survival as assessed by the investigator.ResultsOf the 590 randomised patients, 297 received pyrotinib, trastuzumab, and docetaxel treatment (pyrotinib group), and 293 received placebo, trastuzumab, and docetaxel treatment (placebo group). At data cut-off on 25 May 2022, the median follow-up was 15.5 months. The median progression-free survival according to the investigator was significantly longer in the pyrotinib group than in the placebo group (24.3 (95% confidence interval 19.1 to 33.0) months versus 10.4 (9.3 to 12.3) months; hazard ratio 0.41 (95% confidence interval 0.32 to 0.53); one sided P<0.001). Treatment related adverse events of grade 3 or higher were reported in 267 (90%) of the 297 patients in the pyrotinib group and 224 (76%) of the 293 patients in the placebo group. No treatment related deaths occurred in the pyrotinib group, and one (<1%; diabetic hyperosmolar coma) treatment related death occurred in the placebo group. Survival and toxicities are still under assessment with longer follow-up.ConclusionsPyrotinib, trastuzumab, and docetaxel showed superiority by significantly improving progression-free survival compared with placebo, trastuzumab, and docetaxel in patients with untreated HER2 positive metastatic breast cancer. The toxicity was manageable. The findings support this dual anti-HER2 regimen as an alternative first line treatment option in this patient population.Trial registrationClinicalTrials.gov NCT03863223.

Abstract: Objective: To explore the distribution of estrogen receptors (ER) and progesterone receptors (PR) in patients with breast cancer and to compare the results with clinical parameters. Methods: Breast cancer specimens of 1393 cases were stained for the ER and PR by a SP Two -Step method, and analyzed with respect to age, menstrual status, histopathology and metastasis of axillary lymph nodes. Results: The correlation coefficients between ER and PR were positive-(P< 0.0001). The negative expression of ER in patients 39 years or less was the highest with a statistical significance (P<0.0001 ). There was no relationship between the patient’s age and positive expression of ER, PR and negative expression of PR (P>0.05). There were significantly higher positive rates of ER and lower positive rates of PR in post-menopausaf patients than in pre -menopausal cases(P<0.0001). There was no relationship between the status of ER, PR and the corresponding histopathology (P>0.05). The patients with no metastasis in the axillary lymph nodes had higher simultaneous positive rates of ER and PR (P<0.0001), and those with axillary lymph node metastasis had significantly higher rates of negative expression of ER and PR(P<0.0001). Conclusion: The positive and negative distributions of ER and PR have some regular patterns which may be used as a reference to choose combined therapy and to predict the prognosis for breast cancer patients.