Explore the vast range of titles available.

Obesity can cause chronic metabolic disorders such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver diseases. The aim of this study was to investigate the antiobesity and antidiabetic effects of the dairy bacterium P. freudenreichii MJ2 isolated from raw milk using 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. Lipid accumulation and the expression levels of genes related to lipid metabolism, such as preadipocytic gene ( Pref-1 ), adipogenic genes ( PPARγ and C/EBPα ), and lipogenic genes ( FAS , SCD-1 , and ACC ), significantly decreased in heat-killed P. freudenreichii MJ2 (hkMJ2)-treated adipocytes. Live P. freudenreichii MJ2 (MJ2), hkMJ2, and Lactobacillus plantarum (LP) decreased body weight gain in HFD-induced obese mice compared with the model group. The liver and epididymal white adipose tissue weights in the MJ2-, hkMJ2- and LP-treated groups were significantly lower than those in the model group. The expression levels of genes and proteins related to adipogenesis and lipogenesis significantly decreased and lipolysis (HSL and ATGL) increased in the MJ2-, hkMJ2-, and LP-treated groups. The expression levels of genes related to fatty acid β-oxidation ( CPT-1α and ACOX1 ) increased in the MJ2-, hkMJ2-, and LP-treated groups. In addition, blood glucose and fasting insulin levels in the MJ2- and hkMJ2-treated groups decreased compared with those in the model group. P. freudenreichii MJ2 ameliorate insulin resistance by obesity. In conclusion, both MJ2 and hkMJ2 alleviate obesity and metabolic syndrome.

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student’s t test, p  < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC ( p  < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC ( P  = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC ( P  = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC. Breast cancer: Genomic characteristics of rare subtype examined A comparative study reveals the distinctive genomic and clinical characteristics of a rare form of breast cancer, with implications for treatment. Apocrine carcinoma accounts for 1–4 percent of breast cancer cases. The molecular characteristics of a subtype known as triple negative apocrine carcinoma (TNAC) remain unclear. Ji-Yeon Kim at Sungkyunkwan University School of Medicine, Seoul, South Korea, and co-workers conducted genomic analysis on tumor samples taken from 73 TNAC patients. They compared the results to samples from 32 triple negative breast cancer (TNBC) in which the low expression of Ki-67, a marker protein for cancer proliferation, was similar to the TNAC patients. TNAC patients had different genetic mutations and a better survival outcome than TNBC patients with low Ki-67. Therefore, early-stage TNAC may not require chemotherapy after surgery. Further research into TNAC genomic characteristics is warranted.

The OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician’s choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29–0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients.

Background Participation in exercise, and dietary and nutritional intakes have an impact on the risk and prevalence of metabolic syndrome (MetS), but these effects may differ according to whether a person lives alone or in a multi-person household. We analyzed differences in physical activity (PA) levels and energy intake according to household-type and MetS presence among young adults, to investigate the relationships among these factors. Methods Data of 3974 young adults (aged > 19 years and < 40 years) were obtained from the Korean National Health and Nutrition Examination Survey (2016–2018). We analyzed PA levels (occupational and recreational PA, and transport) and energy intake (total, carbohydrate, protein, and fat). Results Logistic regression data showed that low PA levels and higher energy intake were associated with MetS incidence and its components in young adults, after adjusting for body mass index, smoking, household-type, and sex. Overall, there was no significant difference in PA level between the MetS and non-MetS group. The total energy intake was higher in the MetS than in the non-MetS group ( p  <  0.05). These results were similar to those found in multi-person households. In single-person households, the MetS group had significantly lower PA levels ( p  <  0.01) and total energy intake ( p  <  0.05) than the non-MetS group. Conclusions We found significant association among low PA levels, high energy intake, and MetS components in young Korean adults, but with patterns differing according to household type. Energy intake was higher in young adults with than those without MetS, who lived in multi-person households, while young adults with MetS who lived alone had lower PA levels and lower energy intake than those without MetS. These findings highlight the need for different approaches of implementing PA and nutrition strategies according to the type of household in order to prevent MetS.

The addition of pembrolizumab to platinum-based neoadjuvant chemotherapy significantly increased the percentage of patients with a pathological complete response among patients with locally advanced triple-negative breast cancer. Side effects of the immunotherapy were added to the usual toxic effects of chemotherapy, but most patients completed planned treatment.

In the single-arm, phase 2 DESTINY-Breast01 trial, trastuzumab deruxtecan showed robust activity in patients with HER2-positive metastatic breast cancer who were refractory or resistant to trastuzumab emtansine; a population with scarce effective treatments. In DESTINY-Breast02, we aimed to compare the efficacy and safety of trastuzumab deruxtecan with treatment of physician's choice in this patient population. This randomised, open-label, multicentre, phase 3 trial was conducted at 227 sites (hospitals, university hospitals, clinics, community centres, and private oncology centres) in North America, Europe, Asia, Australia, Brazil, Israel, and Türkiye. Eligible patients were aged 18 years or older, had unresectable or HER2-positive metastatic breast cancer, previously received trastuzumab emtansine, disease progression, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate renal and hepatic function. Patients were randomly assigned (2:1) to receive trastuzumab deruxtecan (intravenously at 5·4 mg/kg once every 3 weeks) or treatment of physician's choice using block randomisation. Treatment of physician's choice was either capecitabine (1250 mg/m2; orally twice per day on days 1–14) plus trastuzumab (8 mg/kg intravenously on day 1 then 6 mg/kg once per day) or capecitabine (1000 mg/m2) plus lapatinib (1250 mg orally once per day on days 1–21), with a 21-day schedule. The primary endpoint was progression-free survival based on blinded independent central review in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03523585. Between Sept 6, 2018, and Dec 31, 2020, 608 patients were randomly assigned to receive trastuzumab deruxtecan (n=406; two did not receive treatment) or treatment of physician's choice (n=202; seven did not receive treatment). 608 (100%) patients were included in the full analysis set. The median age was 54·2 years (IQR 45·5–63·4) in the trastuzumab deruxtecan group and 54·7 years (48·0–63·0) in the treatment of physician's choice group. 384 (63%) patients were White, 603 (99%) were female, and five (<1%) were male. The median follow-up was 21·5 months (IQR 15·2–28·4) in the trastuzumab deruxtecan group and 18·6 months (8·8–26·0) in the treatment of physician's choice group. Median progression-free survival by blinded independent central review was 17·8 months (95% CI 14·3–20·8) in the trastuzumab deruxtecan group versus 6·9 months (5·5–8·4) in the treatment of physician's choice group (HR 0·36 [0·28–0·45]; p<0·0001). The most common treatment-emergent adverse events were nausea (293 [73%] of 404 with trastuzumab deruxtecan vs 73 [37%] of 195 with treatment of physician's choice), vomiting (152 [38%] vs 25 [13%]), alopecia (150 [37%] vs eight [4%]), fatigue (147 [36%] vs 52 [27%]), diarrhoea (109 [27%] vs 105 [54%]), and palmar–plantar erythrodysaesthesia (seven [2%] vs 100 [51%]). Grade 3 or higher treatment-emergent adverse events occurred in 213 (53%) patients receiving trastuzumab deruxtecan versus 86 (44%) receiving treatment of physician's choice; whereas drug-related interstitial lung disease occurred in 42 (10%; including two grade 5 death events) versus one (<1%). DESTINY-Breast02 shows the favourable benefit–risk profile of trastuzumab deruxtecan in patients with HER2 positive metastatic breast cancer, as previously reported in DESTINY-Breast01, and is the first randomised study to show that one antibody-drug conjugate can overcome resistance to a previous one. Daiichi Sankyo and AstraZeneca.

Among persons with breast cancer previously treated with hormonal therapy, the AKT pathway inhibitor capivasertib when added to fulvestrant significantly prolonged progression-free survival as compared with fulvestrant alone.

Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov, NCT03056755. Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5-15·9). 61 (50·4%; 95% CI 41·2-59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. Novartis Pharmaceuticals.

In patients with metastatic HER2-positive breast cancer that had progressed after primary therapy, treatment with the antibody–drug conjugate trastuzumab deruxtecan resulted in a higher response rate and longer progression-free survival than trastuzumab emtansine. Since trastuzumab deruxtecan was associated with interstitial pulmonary fibrosis, close monitoring of pulmonary function is warranted.