Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial.

CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as front-line treatment in women with HER2-positive advanced BC (n = 41) including those with HR-negative disease. The primary endpoint is the objective response rate, and secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of assessable patients have a confirmed objective response, meeting the primary endpoint. The median PFS is 11.0 months (95% CI = 7.3-19.3), and OS data are not mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. These findings suggest that this combination may have promising activity and manageable toxicity. Further investigation is needed.

Temporal patterns of algae in different urban lakes and their correlations with environmental variables in Xi'an, China.

Urban lakes were critical in aquatic ecology environments, but how environmental factors affected the distribution and change characteristics of algal communities in urban lakes of Xi'an city was not clearly. Here, we investigated the algal community structure of six urban lakes in Xi'an and evaluated the effects of water quality parameters on algae. The results indicated that the significant differences on physicochemical parameters existed in different urban lakes. The maximum concentration of total phosphorus in urban lakes was (0.18 ± 0.01) mg/L and there was a phenomenon of phosphorus limitation. In addition, 51 genera of algae were identified and Chlorella sp. was the dominant algal species, which was affiliated with Chlorophyta. Network analysis elucidated that each lake had a unique algal community network and the positive correlation was dominant in the interaction between algae species, illustrating that mature microbial communities existed or occupied similar niches. Redundancy analysis illustrated that environmental factors explained 47.35% variance of algal species-water quality correlation collectively, indicating that water quality conditions had a significant influence on the temporal variations of algae. Structural equation model further verified that algal community structure was directly or indirectly regulated by different water quality conditions. Our study shows that temporal patterns of algal communities can reveal the dynamics and interactions of different urban ecosystem types, providing a theoretical basis for assessing eutrophication levels and for water quality management.

Promoted aerobic denitrification through denitrifying fungal communities: Co-occurrence patterns and treatment of low C/N micro-polluted water.

Despite the growing interest in using mixed-culture aerobic denitrifying fungal flora (mixed-CADFF) for water remediation, there is limited research on their nitrogen removal performance in low C/N polluted water bodies. To address this knowledge gap, we isolated three mixed-CADFFs from overlying water in urban lakes to evaluate their removal performance. The total nitrogen (TN) removal efficiencies were 93.60 %, 94.64 %, and 95.18 %, while the dissolved organic carbon removal efficiencies were 96.64 %, 95.12 %, and 96.70 % for mixed-CADFF LN3, LN7, and LN15, respectively in the denitrification medium under aerobic conditions at 48 h cultivation. The three mixed-CADFFs could utilize diverse types of low molecular weight carbon sources to drive the aerobic denitrification processes efficiently. The optimal C/N ratio for the mixed-CADFFs were C/N = 10, and then C/N = 15, 7, 5, and 2. The high-throughput sequencing analysis of three mixed-CADFFs indicated that Eurotiomycetes, Cystobasidiomycetes, and Sordariomycetes were the dominant class in the communities at class level. The network analysis showed that the rare fungal species, such as Scedosporium dehoogii Saitozyma, and Candida intermedia presented positively co-occurred with the TN removal and organic matter reduction capacity. Immobilization mixed-CADFFs treatment raw water experiments indicated that three mixed-CADFFs could reduce nearly 62.73 % of TN in the low C/N micro-polluted raw water treatment. Moreover, the cell density and cell metabolism indexes were also increased during the raw water treatment. This study will provides new insight into resource utilization of the mixed-culture aerobic denitrifying fungal community in field of environment restoration.

Effects of copper sulfate algaecide on the cell growth, physiological characteristics, the metabolic activity of Microcystis aeruginosa and raw water application.

Harmful cyanobacteria blooms (HCBs) occurred frequently and become a serious scientific challenge. Copper sulfate (CuSO4) is a broad-spectrum chemical algaecide to control algae blooms. Herein, the Microcystis aeruginosa was exposed to different CuSO4 (0.0, 0.2 and 0.5 mg/L) to assess the variations in algal physiological process and metabolic profiles. The results indicated that exposure to CuSO4 of 0.5 mg/L at 72 h could significantly inhibit the cell growth and photosynthetic capacity of M. aeruginosa, including chl-a content and chlorophyll fluorescence parameters. Plasma membrane damage causing cell lysis of M. aeruginosa increased the K+ release. The increase of SOD and CAT suggested that CuSO4 treatment caused oxidative stress in algal cells. Different doses of CuSO4 modified the carbon metabolic potential, algal cells had their unique metabolic mode thereby. Moreover, the research further verified that CuSO4 would also inhibit algal growth and change algal community structure in site-collected water application. Overall, laboratory results of M. aeruginosa to CuSO4 and site-collected water application of algal responses to CuSO4 might be conducive to uncovering the controlling mechanism of algae and the potential effect of carbon cycling in an ecological environment.

Clinicopathological features and prognosis of breast cancer combined with symptomatic bone marrow metastases: A 10-year, single-center, real-world study of 67 cases.

PURPOSE: Bone marrow metastasis (BMM) is uncommon in breast cancer (BC), and early diagnosis is challenging. BMM lacks definitive treatment options and poses a great threat to the survival of patients. Herein, we investigated the clinical features, prognosis, and factors affecting the prognosis of BC patients with symptomatic BMM to help improve the understanding of this disease and provide effective diagnostic and treatment strategies. METHODS: Clinical data of 67 patients with BC and BMM were retrospectively analyzed for clinical characteristics, treatment, and prognosis of BMM. Univariate and multivariate analyses were performed to determine factors affecting overall survival following BMM (BMMOS). RESULTS: Among patients with BMM, 86.6% were diagnosed after bone metastasis (BM), while 13.4% were diagnosed simultaneously with BM. A total of 73.1%, 13.4%, and 13.4% of the patients had hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) tumors, HER2+ tumors, and triple-negative tumors, respectively. The most common symptoms of BMM were the coexistence of anemia and thrombocytopenia (26.9%), anemia (19.4%), and pancytopenia (17.9%). The median BMMOS was 7.6 months (95% CI, 3.9-11.3). Univariate and multivariate analyses showed that BMMOS was associated with platelet count <75 × 109 /L at the time of BMM diagnosis. The BMMOS of patients who underwent endocrine therapy, combined chemotherapy, and mono-chemotherapy after BMM was 15.7, 9.7, and 8.6 months, respectively, whereas that of untreated patients was 2.9 months, and the difference among the results was statistically significant (χ2  = 20.102, p < 0.0001). Changes in patient hemogram and/or body temperature during treatment were consistent with the overall effect of the disease (p < 0.0001). CONCLUSION: BMM should be considered in BC patients with BM, an unexplained reduction in hemogram parameters, especially anemia and thrombocytopenia, and/or fever without chills. Active, effective, individualized treatment strategies can prolong BMMOS.

Aerobic Denitrification Enhanced by Immobilized Slow-Released Iron/Activated Carbon Aquagel Treatment of Low C/N Micropolluted Water: Denitrification Performance, Denitrifying Bacterial Community Co-occurrence, and Implications.

The key limiting factors in the treatment of low C/N micropolluted water bodies are deficient essential electron donors for nitrogen removal processes. An iron/activated carbon aquagel (IACA) was synthesized as a slowly released inorganic electron donor to enhance aerobic denitrification performance in low C/N micropolluted water treatment. The denitrification efficiency in IACA reactors was enhanced by more than 56.72% and the highest of 94.12% was accomplished compared with those of the control reactors. Moreover, the CODMn removal efficiency improved by more than 34.32% in IACA reactors. The Illumina MiSeq sequencing consequence explained that the denitrifying bacteria with facultative denitrification, iron oxidation, and iron reduction function were located in the dominant species niches in the IACA reactors (e.g., Pseudomonas, Leptothrix, and Comamonas). The diversity and richness of the denitrifying bacterial communities were enhanced in the IACA reactors. Network analysis indicated that aerobic denitrifying bacterial consortia in IACA reactors presented a more complicated co-occurrence structure. The IACA reactors presented the potential for long-term denitrification operation. This study affords a pathway to utilize IACA, promoting aerobic denitrification during low C/N micropolluted water body treatment.

Aerobic denitrifying using actinobacterial consortium: Novel denitrifying microbe and its application.

The aerobic denitrifying capacity of actinomycete strain has been investigated recently, while little is known about nitrogen and carbon substrate removal by mix-cultured aerobic denitrifying actinobacteria (Mix-CADA) community. Hence, three Mix-CADA consortiums, named Y23, X21, and Y27, were isolated from urban lakes to investigate their aerobic denitrification capacity, and their removal efficiency for nitrate and dissolved organic carbon were >97 % and 90 %, respectively. Illumina Miseq sequencing revealed that Streptomyces was the most dominant genus in the Mix-CADA consortium. Network analysis indicated that Streptomyces exfoliates, as the core species in the Mix-CADA consortium, majorly contributed to dissolved organic carbon and total nitrogen reduction. Moreover, the three Mix-CADA consortiums could remove 78 % of the total nitrogen and 61 % of the permanganate index from the micro-polluted l water. Meanwhile, humic-like was significantly utilized by three Mix-CADA consortiums, whereas Mix-CADA Y27 could also utilize aromatic protein and soluble microbial by-product-like in the micro-polluted raw water purification. In summary, this study will offer a novel perspective for the purification of micro-polluted raw water using the Mix-CADA consortium.

Novel insights into aerobic denitrifying bacterial communities augmented denitrification capacity and mechanisms in lake waters.

Scanty attention has been paid to augmenting the denitrification performance of polluted lake water by adding mix-cultured aerobic denitrifying bacterial communities (Mix-CADBCs). In this study, to solve the serious problem of nitrogen pollution in lake water bodies, aerobic denitrifying bacteria were added to lake water to enhance the nitrogen and carbon removal ability. Three Mix-CADBCs were isolated from lake water and they could remove >94 % of total nitrogen and dissolved organic carbon, respectively. The balance of nitrogen analysis shown that >70 % of the initial nitrogen was converted to gaseous nitrogen, and <11 % of the initial nitrogen was converted into microbial biomass. The batch experiments indicated that three Mix-CADBCs could perform denitrification under various conditions. According to the results of nirS-type sequencing, the Hydrogenophaga sp., Prosthecomicrobium sp., and Pseudomonas sp. were dominated genera of three Mix-CADBCs. The analysis of network indicated Pseudomonas I.Bh25.14 and Vogsella LIG4 were correlated with the removal of total nitrogen (TN) and dissolved organic carbon in the Mix-CADBCs. Compared with lake raw water, the addition of three Mix-CADBCs could promote the denitrification capacity (the removal efficiencies of TN > 78.72 %), microbial growth (optical density increased by 0.015-0.138 and the total cell count increased by 2 times), and organic degradation ability (the removal efficiency chemical oxygen demand >38 %) of lake water. In general, the findings of this study demonstrated that Mix-CADBCs could provide a new perspective for biological treatment lake water body.

Nitrogen reduction by aerobic denitrifying fungi isolated from reservoirs using biodegradation materials for electron donor: Capability and adaptability in the lower C/N raw water treatment.

Biological denitrification was considered an efficient and environmentally friendly way to remove the nitrogen in the water body. However, biological denitrification showed poor nitrogen removal performance due to the lack of electron donors in the low C/N water. In this study, three novel aerobic denitrifying fungi (Trichoderma sp., Penicillium sp., and Fusarium sp.) were isolated and enhanced the performance of aerobic denitrification of fungi in low C/N water bodies combined with polylactic acid/polybutylene adipate-co-terephthalate (PLA/PBAT). In this work, the aerobic denitrifying fungi seed were added to denitrifying liquid medium and mixed with PLA/PBAT. The result showed that Trichoderma sp., Penicillium sp., and Fusarium sp. could reduce 89.93 %, 89.20 %, and 87.76 % nitrate. Meanwhile, the nitrate removal efficiency adding PLA/PBAT exceeded 1.40, 1.68, and 1.46 times that of none. The results of material characterization suggested that aerobic denitrifying fungi have different abilities to secrete proteases or lipases to catalyze ester bonds in PLA/PBAT and utilize it as nutrients in denitrification, especially in Penicillium brasiliensis D6. Besides, the electron transport system activity and the intracellular ATP concentration were increased significantly after adding PLA/PBAT, especially in Penicillium brasiliensis D6. Finally, the highest removal efficiency of total nitrogen in landscape water by fungi combined with PLA/PBAT was >80 %. The findings of this work provide new insight into the possibility of nitrogen removal by fungi in low C/N and the recycling of degradable resources.

Characterization of non-taste & odor produced aerobic denitrification actinomycetes strains Streptomyces spp. isolated from reservoir ecosystem: Denitrification performance and carbon source metabolism.

The aerobic denitrification performance of actinomycetes was investigated. Two strains of actinomycetes were isolated and identified as Streptomyces sp. LJH-12-1 and Streptomyces diastatochromogenes LJH-12-2. Strain LJH-12-1 could remove 94% of organic carbon and 91% of total nitrogen. Meanwhile, strain LJH-12-2 could reduce 96% of organic carbon and 93% of total nitrogen. Two strains of actinomycetes revealed excellent carbon source metabolism activity. Moreover, the total nitrogen removal efficiencies were 69%, and 54%, respectively for strains LJH-12-1, and LJH-12-2 during the micro-polluted landscape raw water treatment. Futhermore, strains LJH-12-1 and LJH-12-2 could utilize aromatic proteins, soluble microbial products, and humic acid to drive aerobic denitrification processes in the landscape water bodies. These results will provide a new insight into applying aerobic denitrification actinomycetes to treat micro-polluted water bodies.

Diagnostic diversity and heterogeneity of tumors: a real-world study of metastasis re-biopsy in advanced breast cancer.

BACKGROUND: Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions. METHODS: We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients' demographic profiles and disease characteristics. RESULTS: In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies. CONCLUSIONS: The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.

Mix-cultured aerobic denitrifying bacteria augmented carbon and nitrogen removal for micro-polluted water: Metabolic activity, coexistence and interactions, and immobilized bacteria for reservoir raw water treatment.

Less attention has been paid on the oligotrophic water body nitrogen treatment with mix-cultured aerobic denitrifying bacteria (Mix-CADB). In this study, three Mix-CADB communities were screened from the sediments of reservoirs. The nitrate and dissolved organic carbon (DOC) removal efficiencies of Mix-CADB communities were higher than 92 % and 91 %, respectively. Biolog results suggested that Mix-CADB communities displayed excellent carbon source metabolic activity. The nirS gene sequencing indicated that Pseudomonas sp. and Pseudomonas stutzeri accounted for more proportions in the core species of three Mix-CADB communities. The network model revealed that Pseudomonas sp. and Pseudomonas stutzeri mainly drove the total nitrogen and DOC removal of Mix-CADB communities. More importantly, the immobilized Mix-CADB communities could reduce >91 % nitrate in the adjusted reservoir raw water. Overall, this study showed that the three Mix-CADB communities could be regarded as potential candidates for the nitrogen treatment in oligotrophic water body ecosystems.

Cooperation triggers nitrogen removal and algal inhibition by actinomycetes during landscape water treatment: Performance and metabolic activity.

The actinomycetes strain Streptomyces sp. XD-11-9-3 and Streptomyces sp. 5 were isolated and presented poor denitrification performance. Co-culture of actinomycetes triggers nitrogen removal capacity under aerobic conditions (reduced 96% of total nitrogen). Nitrogen balance analysis presented that 71% of initial nitrogen converted as gaseous nitrogen. Moreover, co-culture increased the concentrations of adenosine triphosphate (>2.1 folds) and electron-transmission system activity (>1.5 folds) significantly. The co-culture presented excellent carbon source metabolism activity (especially amines and carboxylic acids) compared with monoculture. The removal efficiency of total nitrogen in the micro-polluted landscape water water reached 61% in the co-culture system, and the algal survival could be inhibited significantly. However, the dominant niche of the co-culture system restrained the diversity of the indigenous nirS-type denitrifying bacterial community. This study provided a novel pathway to the research of co-culture inefficiency aerobic denitrifier and further application in the restoration of polluted water.

Nitrogen removal from low carbon/nitrogen polluted water is enhanced by a novel synthetic micro-ecosystem under aerobic conditions: Novel insight into abundance of denitrification genes and community interactions.

The main limiting factor in treatment of wastewater with a low carbon/nitrogen ratio is insufficient electron donors for aerobic denitrification. A novel synthetic micro-ecosystem (SM) with functional materials as the core structure was prepared to enhance nitrate removal during wastewater treatment. Nitrate removal in the reactors with SM increased by more than 40 % and reached 97.43 % under aerobic conditions. The abundance of denitrification functional genes in activated sludge increased by 2.7 folds after adding SM. Network analysis showed that the denitrifying bacterial community in the reactors with SM displayed a more abundant symbiotic structure. In the reactors with SM, bacteria with both denitrification and inorganic electron transfer capabilities (such as Paracoccus sp., Thaurea sp., and Achromobacter sp.) occupied dominant niche. A species abundance distribution model indicated more intense competition for the dominant niche for the denitrification community in the reactor with SM. Thus, SM promotes denitrification in polluted water bodies under aerobic conditions.

Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial.

BACKGROUND: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. METHODS: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. FINDINGS: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. FUNDING: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Distress Thermometer in breast cancer: systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to reach a summarised estimate of distress prevalence screened by Distress Thermometer (DT) among patients with breast cancer and compare different pooled prevalence estimated between different subgroups. METHODS: Two independent interviewers conducted a systematic search from PubMed, EMBASE, Ovid and Cochrane Library and checked related reviews and meta-analyses for eligible studies. The studies that identified distress of patients with breast cancer with DT were included. After extracting demographic characteristics and distress prevalence, the pooled analysis and the forest plot were completed by using STATA V.12.0 software. We conducted a subgroup analysis based on demographic and methodological characteristics of the studies. The publication bias was estimated by funnel plot. RESULTS: Seventeen studies describing 3870 patients with breast cancer were included in this meta-analysis. The distress prevalence of patients with breast cancer varied from 25.3% to 71.7% among these studies. The pooled distress prevalence was 50% (95% CI 49% to 52%) for the overall sample. The pooled distress prevalence rates in DT ≥7, DT ≥5 and DT ≥4 subgroups were 37% (95% CI 35% to 40%), 45% (95% CI 40% to 49%) and 62% (95% CI 60% to 65%), respectively. The distress prevalence had statistically significant differences between subgroups, which were differentiated by the initial time of distress identified, papers' publication time, patients' average age and country. There was no publication bias among the included studies. CONCLUSION: The distress prevalence was high among patients with breast cancer. Routine and timely screening of distress for patients with breast cancer is of great significance in oncology management.

Serum exosomal miR-377-3p and miR-381-3p as diagnostic biomarkers in colorectal cancer.

Aim: This study aimed to identify specific and sensitive exosomal miRNAs in diagnosing patients with colorectal cancer (CRC). Methods: Serum exosomes were isolated from 175 CRC patients and 172 healthy donors by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was detected by quantitative PCR and the results analyzed by receiver operating characteristic analysis to illuminate the diagnostic accuracy. Results: Both exosomal miR-377-3p and miR-381-3p were downregulated in CRC patients as well as in early-stage patients compared with healthy donors; they could serve as circulating biomarkers of diagnosis, including early diagnosis, for CRC, possessing favorable diagnostic efficiency. Conclusion: Exosomal miR-377-3p and miR-381-3p levels were downregulated in CRC patients and may be useful as novel and specific biomarkers for the diagnosis of CRC, especially early-stage CRC.

Major depressive symptoms in breast cancer patients with ovarian function suppression: a cross-sectional study comparing ovarian ablation and gonadotropin-releasing hormone agonists.

BACKGROUND: Ovarian function suppression (OFS) is indicated in premenopausal women with early or metastasis breast cancer, which may be achieved with similar effect by gonadotropin-releasing hormone agonists (GnRHa) or ovarian ablation (OA). We examined whether there were differences in major depressive symptoms outcomes and its associated factors between gonadotropin-releasing hormone agonists (GnRHa) and ovarian ablation (OA) in premenopausal breast cancer patients. METHODS: Premenopausal breast cancer patients from seven hospitals who received OFS participated in the study between June 2019 and June 2020. The correlated variable was the type of ovarian suppression, categorized as either OA (n = 174) or GnRHa (n = 389). Major depressive symptoms was evaluated using the Patient Health Questionnaire (PHQ-9), and the Female Sexual Function Index questionnaire was used to assess sexual function. RESULTS: A total of 563 patients completed the surveys. The mean PHQ-9 sum score was slightly lower in the GnRHa cohort than in the OA cohort (11.4 ± 5.7 vs. 12.8 ± 5.8, P = 0.079). There were significantly fewer patients with major depressive symptoms (PHQ-9 ≥ 15) in the GnRHa cohort (31.1% vs. 40.2%, Exp (B)=1.805, P=0.004). Further, breast-conserving surgery and sexual dysfunction were negatively correlated with major depressive symptoms [mastectomy vs. breast-conserving: Exp (B) = 0.461, P <0.001;[sexual dysfunction vs. normal: Exp (B) = 0.512, P = 0.001]. CONCLUSIONS: This is the first study to demonstrate that GnRHa results in more favorable depressive symptoms outcomes than OA. Moreover, most patients preferred alternatives to their OFS treatment. These findings can contribute to improving and alleviating the adverse effects of OFS.

Efficacy and safety of bevacizumab-containing therapy for refractory advanced breast cancer: a retrospective study.

BACKGROUND: Advanced breast cancer (ABC) is difficult to treat due to the primary and acquired resistance, which is the main cause of rescue treatment failure. Thus, developing a new rescue treatment strategy for clinicians is a challenge. This study retrospectively collected the medical information of patients with refractory ABC who were treated with bevacizumab at our department to analyze the efficacy and safety of bevacizumab-containing therapy as a new treatment method for refractory ABC. METHODS: The complete medical information of patients receiving bevacizumab treatment from November 2017 to November 2020 was collected, and patients' general medical history and disease characteristics were analyzed. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to failure (TTF), overall survival (OS), and safety were also analyzed using SPSS 20.0 statistical software. RESULTS: The data of 68 women with refractory ABC who received bevacizumab-containing therapy were collected. The last follow-up examinations were performed on March 31, 2021. The ORR was 41.2% and the DCR was 88.2%. The median PFS, TTF, and OS were 6.0 months [95% confidence interval (CI): 3.4-8.6 months], 4.0 months (95% CI: 3.2-4.8 months), and 26.6 months (95% CI: 10.2-43.0 months), respectively. Treatment was discontinued in 2 patients due to chemo-related adverse reactions. The main adverse events related to bevacizumab were hypertension (7.4%) and bleeding (2 cases, 2.9%), both of which were grade 1. No specific adverse events causing the discontinuation of bevacizumab treatment were observed in the other patients. CONCLUSIONS: Among patients with refractory ABC, bevacizumab-containing therapy is feasible and safe, and can be used as a new treatment strategy. However, the question of who can benefit the most from bevacizumab-containing therapy requires further exploration.