METHODS: The proliferative effect of the identified protein on MCF-7 cells that interacted non-adhesively with BMSCs pre-treated with pioglitazone and/or rosiglitazone was evaluated using cell culture inserts and conditioned media. The mRNA expression of proliferation and lipid accumulation markers was also evaluated in the interacted MCF-7 cells by reverse transcription-quantitative PCR. Finally, the correlation between the identified protein and fibroblast growth factor 4 (FGF-4) protein in the conditioned media of the pre-treated BMSCs was evaluated by ELISA.
RESULTS: The present study identified vimentin as the specific protein among the complex intracellular proteins that likely plays a role in MCF-7 cell proliferation when the breast cancer cells interacted non-adhesively with BMSCs pre-treated with a combination of pioglitazone and rosiglitazone. The inhibition of this protein promoted the proliferation of MCF-7 cells when the breast cancer cells interacted with pre-treated BMSCs. Gene expression analysis indicated that pre-treatment of BMSCs with a combination of pioglitazone and rosiglitazone decreased the mRNA expression of Ki67 and proliferating cell nuclear antigen in MCF-7 cells. The pre-treatment did not induce mRNA expression of PPARγ, which is a sign of lipid accumulation. The level of vimentin protein was also associated with the FGF-4 protein expression level in the conditioned media of the pre-treated BMSCs. Bioinformatics analysis revealed that vimentin regulated the expression of FGF-4 through its interaction with SRY-box 2 and POU class 5 homeobox 1.
CONCLUSIONS: The present study identified a novel intracellular protein that may represent the promising target in pre-treated BMSCs to decrease the proliferation of breast cancer MCF-7 cells for human health and wellness.
METHODS: Studying breast cancer, we established genome-scale DNA methylation profiles of prospectively collected buffy coat samples (n = 702) from a case-control study nested within the EPIC-Heidelberg cohort using reduced representation bisulphite sequencing (RRBS).
RESULTS: We observed cancer-specific DNA methylation events in buffy coat samples. Increased DNA methylation in genomic regions associated with SURF6 and REXO1/CTB31O20.3 was linked to the length of time to diagnosis in the prospectively collected buffy coat DNA from individuals who subsequently developed breast cancer. Using machine learning methods, we piloted a DNA methylation-based classifier that predicted case-control status in a held-out validation set with 76.5% accuracy, in some cases up to 15 years before clinical diagnosis of the disease.
CONCLUSIONS: Taken together, our findings suggest a model of gradual accumulation of cancer-associated DNA methylation patterns in peripheral blood, which may be detected long before clinical manifestation of cancer. Such changes may provide useful markers for risk stratification and, ultimately, personalized cancer prevention.
OBJECTIVE: To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up.
DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment.
INTERVENTIONS: In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years.
MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS).
RESULTS: A total of 538 female patients were included (median age, 51 years [range, 22-65 years]). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient [0.4%]; TRZ, 2 [0.7%]). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients [SB3, n = 267; TRZ, n = 271]). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio [HR], 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group.
CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02771795.
METHODS: Time to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks.
RESULTS: The average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p breast health or breast cancer symptoms (36.3%), regardless of help-seeking behaviour (p = 0.931). Unexpectedly, women with no delay (9 days average) and great delay (259 days average) were more similar to each other than to women with mild delays (58 days average), but, women who experienced great delay reported poor motivation due to fear and embarrassment (p = 0.066) and a lack of social support (p = 0.374) to seek help.
CONCLUSIONS: Down-staging of breast cancer in Malaysia will require a multi-pronged approach aimed at modifying culturally specific social and emotional barriers, eliminating misinformation, and instilling motivation to seek help for breast health for the women most vulnerable to help-seeking delays.
MATERIALS AND METHODS: This cross-sectional study was conducted on 124 breast cancer outpatients within the first year of diagnosis and yet to commence oncological treatment. Body composition parameters [body weight, body mass index (BMI), body fat percentage, fat mass over fat-free mass ratio (FM/FFM), muscle mass, and visceral fat] were obtained using a bioelectrical impedance analyzer. Body fat percentage was categorized into two groups which were normal (<35%) and high (≥35%). The E-DII was calculated from the validated 165-items Food Frequency Questionnaire (FFQ) and categorized into three groups or tertiles. Multiple logistic regression analysis was used to determine the association between the E-DII and body fat percentage.
RESULTS: Mean body weight, body fat percentage, FM/FFM, and visceral fat increased as E-DII increased from the lowest tertile (T1) to the most pro-inflammatory tertile (T3) (p for trend <0.05). E-DII was positively associated with body fat percentage (OR 2.952; 95% CI 1.154-7.556; p = 0.024) and remained significant after adjustment for cancer stage, age, physical activity, ethnicity, smoking history, and presence of comorbidities. Compared to T1, participants in T3 had a significantly lower consumption of fiber, vitamin A, beta-carotene, vitamin C, iron, thiamine, riboflavin, niacin, vitamin B6, folic acid, zinc, magnesium, and selenium, but a higher intake of total fat, saturated fat, and monounsaturated fatty acids.
CONCLUSIONS: A higher E-DII was associated with increased body fat percentage, suggesting the potential of advocating anti-inflammatory diet to combat obesity among newly diagnosed breast cancer patients.
METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).
RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).
CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.
TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).