Breast Cancer最新文献

Background: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals face significant health disparities worldwide, particularly in preventive medicine. In Japan, where breast cancer has the highest incidence rate among women, understanding screening behaviors among LGBTQ individuals is crucial for improving public health outcomes.

Objective: This study aimed to elucidate the relationship between LGBTQ status and breast cancer screening behaviors in Japan, identifying factors influencing screening uptake and highlighting challenges in health management for the LGBTQ community.

Methods: Using data from the Japan COVID-19 and Society Internet Survey (JACSIS), we analyzed breast cancer screening status among 11,056 biological females. Multinomial logistic regression and stratified regression analyzes were employed to examine factors associated with screening behavior, comparing LGBTQ and non-LGBTQ groups.

Results: LGBTQ individuals demonstrated significantly lower odds of undergoing breast cancer screening (OR 0.82, 95% CI 0.73-0.91, p < 0.001) compared to non-LGBTQ individuals. Key factors influencing lower screening rates among individuals in the survey were primarily linked to LGBTQ identity, followed by higher rates of being uninsured, unmarried status, lower income levels, alcohol consumption. Stratified analysis revealed that uninsured LGBTQ individuals had significantly lower odds of screening (OR 0.23, 95% CI 0.08-0.70, p = 0.01) compared to those with national health insurance.

Conclusion: This study identifies noteworthy differences in breast cancer screening behaviors between LGBTQ and non-LGBTQ individuals in Japan, as indicated by lower odds of screening participation among LGBTQ individuals, even after adjusting for socioeconomic factors. Findings underscore the need for targeted interventions, including improved healthcare access, LGBTQ-friendly medical environments, and awareness campaigns to address these disparities and promote health equity within the LGBTQ community.

Background: This study evaluates the reproducibility of the IRSN-23 model, which classifies patients into highly chemotherapy-sensitive (Gp-R) or less-sensitive (Gp-NR) groups based on immune-related gene expression using DNA microarray analysis, and its impact on breast cancer subtype classification.

Methods: Tumor tissues from 146 breast cancer patients receiving neoadjuvant chemotherapy (paclitaxel-FEC) ± trastuzumab at Osaka University Hospital (OUH) were used to classify patients into Gp-R or Gp-NR using IRSN-23. The ability to predict a pathological complete response (pCR) was assessed and the results were validated with independent public datasets (N = 1282).

Results: In the OUH dataset, the pCR rate was significantly higher in the Gp-R group than in the Gp-NR group without trastuzumab (29 versus 1%, P = 1.70E-5). In all validation sets without anti-HER2 therapy, the pCR rate in the Gp-R group was significantly higher than that in the Gp-NR group. The pooled analysis of the validation set showed higher pCR rates in the Gp-R group than in the Gp-NR group, both without (N = 1103, 40 versus 12%, P = 2.02E-26) and with (N = 304, 49 versus 35%, P = 0.017) anti-HER2 therapy. Collaboration analyses of IRSN-23 and Oncotype Dx or PAM50 could identify highly chemotherapy-sensitive groups and refine breast cancer subtype classification based on the tumor microenvironment (offensive factor-PAM50 and defensive factor-IRSN-23), and the immune subtype was correlated with a better prognosis after NAC.

Conclusions: This study offers new validation analyses of IRSN-23 in predicting chemotherapy efficacy, showing high reproducibility. The findings indicate the clinical value of using IRSN-23 for refining breast cancer subtype classification, with implications for personalized treatment strategies and improved patient outcomes.

Background: Poor prognosis of triple-negative breast cancer (TNBC) is owing to its intrinsic heterogeneity and lack of targeted therapies. Emerging evidence has characterized that targeting c-Myc might be a promising way to treat TNBC.

Methods: c-Myc knocked down TNBC cells were generated and the tamoxifen sensitivity was determined. Methylation-specific PCR analysis was used to detect the methylation status of ERα promoter, and c-Myc-mediated miRNA transcription was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. The in vivo tamoxifen sensitivity was determined by mouse xenograft model.

Results: c-Myc knockdown in TNBC cells leads to the reactivation of ERα and consequent acquisition its sensitivity to tamoxifen. c-Myc depletion decreased the methylation in the promoter of ERα and DNMT1 was identified as the main executor. c-Myc knockdown-induced tamoxifen sensitivity was reversed by DNMT1 overexpression. The expression of miR-152-3p and miR-148a-3p was largely induced in c-Myc knockdown TNBC cells, and both miR-152-3p and miR-148a-3p could target DNMT1 to regulate its expression. c-Myc binds to the promoter regions of miR-152-3p and miR-148a-3p to exert transcriptional suppression. By suppressing miR-152-3p or miR-148a-3p expression using inhibitors, enhanced sensitivity to tamoxifen induced by c-Myc knockdown was partially reversed. In vivo xenograft tumor model demonstrated that c-Myc knockdown mildly inhibits the growth of tumor, and a dramatic decline was observed when administrated with tamoxifen combined with c-Myc knockdown.

Conclusion: Our study first illustrated that c-Myc knockdown in TNBC cells reactivate ERα expression in a miR-152/miR-148a-DNMT1-dependent manner, and brought new sights into treating TNBC using hormonal therapies.

Background: The single-nucleotide polymorphism rs6507583 at the promoter of SET-binding protein 1 (SETBP1) was implicated in estrogen receptor (ER)-positive breast carcinogenesis. Here, we evaluated the clinical and biological relevance of SETBP1 expression in ER-positive breast cancer (BC).

Methods: The associations between SETBP1 expression and clinical outcomes in BC patients were analyzed in independent cohorts. The localizations of SETBP1 expression in BC tissues were observed by immunohistochemical staining. Pathway analyses were conducted using TCGA dataset. In vitro proliferation assay, protein phosphatase 2A (PP2A) activity assay, and gene expression analysis were performed in SETBP1-knockdown ER-positive BC cells. We investigated the factors influencing SETBP1 mRNA expression using TCGA dataset. rs6507583 presence and SETBP1 mRNA expression in 11 mammary cell lines and 56 BC tissue samples were examined by target sequencing and RT-qPCR, respectively.

Results: SETBP1 was downregulated in BC cells compared with normal ductal epithelial cells. Low SETBP1 mRNA expression was an independent prognostic factor for poor recurrence-free survival. Pathway analyses revealed an inverse relationship between decreased SETBP1 expression and the expression of E2F, MYC, and G2M checkpoint target genes in BC tissues. SETBP1 knockdown promoted proliferation, inhibition of PP2A activity, and phosphorylation of MAPK in ER-positive BC. Low SETBP1 expression was influenced by high SETBP1 promoter methylation and DNA copy number SETBP1 deletion. SETBP1 expression with rs6507583 was lower than without rs6507583 in BC.

Conclusions: We demonstrated that low SETBP1 expression could be a poor prognostic biomarker that promotes ER-positive BC proliferation, possibly via phosphorylation of MAPK.

Background: Immune and inflammatory blood parameters have been reported as biomarkers for treatment efficacy. This study aimed to establish a predictive model that includes blood parameters for patients with metastatic breast cancer treated with eribulin.

Methods: A total of 297 patients were enrolled, and their baseline neutrophil-to-lymphocyte ratio, absolute lymphocyte count (ALC), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH), C-reactive protein (CRP), and clinical data were retrospectively collected.

Results: We constructed nomograms to predict overall survival (OS) and progression-free survival (PFS) using blood parameters, including clinical factors. For OS, menopausal status, hormone receptor status, HER2 status, de novo or recurrent, metastatic site, treatment line, ALC, PLR, PNI, LMR, LDH, and CRP were selected to predict the model. We used menopausal status, hormone receptor status, HER2 status, treatment line, PLR, LMR, LDH, and CRP to predict PFS. Both the OS and PFS of patients according to the risk scores were significantly different (p < 0.001). The optimism-corrected C-indices of the nomograms for OS and PFS were 0.680 and 0.622, respectively. The mean time-dependent area under the receiver operating curve values for OS at 1, 2, and 3 years were 0.752, 0.761, and 0.784, respectively, and for PFS at 3, 6, and 12 months were 0.660, 0.661, and 0.650, respectively.

Conclusion: Nomograms incorporating peripheral blood parameters may improve the accuracy of predicting OS and PFS in patients treated with eribulin. Our prediction model may help decision-making for breast cancer patients who are considering eribulin treatment.

Background: The safety of combination therapy with abemaciclib and hormone therapy in patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) who were previously treated with chemotherapy for MBC remains unclear. Caution is required as the Pharmaceuticals and Medical Devices Agency (PMDA) and the U.S. Food and Drug Administration (FDA) have issued warnings about abemaciclib-induced interstitial lung disease (ILD).

Methods: This study was a secondary analysis of a prospective observational study involving patients who had previously undergone chemotherapy for HR + MBC. A certificated respiratory specialist reviewed the clinical information of patients who were suspected of having ILD to adjudicate abemaciclib-induced ILD and definitively diagnosed abemaciclib-induced ILD. In this study, the incidence, risk factors, and clinical course of interstitial lung disease (ILD) are reported.

Results: All cases of patients who received abemaciclib had no radiological evidence of ILD prior to abemaciclib treatment. The incidence of abemaciclib-induced ILD was 7.4% (n = 9/122). CTCAE grade 1/2 occurred in 77.8% (n = 7), with no grade 4/5 cases. The timing of ILD onset varied and our study did not identify any significant risk factors for abemaciclib-induced ILD. All cases of ILD ultimately were confirmed to be in remission or cured.

Conclusion: In this multicenter prospective cohort study with a follow-up period of 3.3 years and a definition of ILD by a certified pulmonologist, we accurately evaluated abemaciclib-associated ILD after chemotherapy. The favorable clinical course of ILD indicate that abemaciclib treatment is an acceptable option for these MBC patients. However, because abemaciclib-induced ILD is difficult to predict, careful monitoring is required during abemaciclib treatment.

Purpose: The radiotherapy categorical anxiety scale (RCAS) was designed to evaluate the specific types of radiation therapy (RT)-related anxiety in cancer patients. We translated RCAS into Chinese, evaluated its reliability and validity in breast cancer (BC) patients, and used it to evaluate changes in specific types and levels of RT-related anxiety throughout RT.

Methods: This was a prospective, longitudinal study enrolling 504 Chinese BC patients receiving RT. The patients completed questionnaires assessing the specific types of RT-related anxiety (our Chinese version of RCAS), depression [Patient Health Questionnaire-9 (PHQ-9)], and anxiety [Generalized Anxiety Disorder-7 (GAD-7)] before, during, and after RT. Emotional distress (ED) was defined as a PHQ-9 or GAD-7 score of > 4. Generalized estimating equation was performed to evaluate changes in total and subscale scores on RCAS. Multivariable general linear models were used to explore independent predictors of baseline RCAS scores.

Results: Our Chinese version of RCAS demonstrated high internal consistency (Cronbach's α = 0.89-0.92). Our data demonstrated a Kaiser-Meyer-Olkin measure of 0.946 and P < 0.001 on the Bartlett sphericity test, indicating their suitability for subsequent confirmatory factor analysis (CFA). CFA further demonstrated its adequate convergent and discriminant validity. The levels of anxiety related to RT environment decreased over time, whereas those of anxiety related to RT treatment efficacy remained stable throughout the treatment. Patients demonstrated higher scores on items regarding side effects and treatment efficacy of RT than on other items. ED before RT independently predicted for higher baseline RCAS score.

Conclusions: Our Chinese version of the RCAS can be used to quantitatively evaluate specific types of RT-related anxiety in Chinese BC patients. Clinicians should pay more attention to anxiety regarding the side effects and treatment efficacy of RT reported by their patients, particularly those with baseline ED.

Background: In the realm of surgical therapy for cN0 early breast cancer, sentinel lymph node biopsy (SNB) has been established as a technique that allows the omission of axillary lymph node dissection (Ax) while maintaining local control in the axillary region.

Methods: This retrospective study analyzed data from 52 patients who underwent reSNB for IBTR after initial breast-conserving surgery at Kanagawa Cancer Center between June 2012 and March 2019. reSNB was conducted using both the dye and radioactive isotope methods. The identification rate was defined as the number of cases in which sentinel lymph nodes were visualized on lymphoscintigraphy images divided by the total number of cases. The identification rate was compared according to the initial surgical procedure.

Results: Overall, the identification rate for reSNB was 94.2%. The identification rate for reSNB in the axilla was higher in patients who initially underwent SNB than in those who initially underwent axillary lymph node dissection (83.3% vs. 42.9%). ReSNB positivity was observed in three patients (6.7%) in the ipsilateral axilla, whereas no metastasis was detected in the contralateral axilla or internal mammary region. Although four cases of recurrence were observed after reoperation, there was no local recurrence in the ipsilateral axillary region.

Conclusions: reSNB demonstrated high identification rates, comparable to those of initial SNB, with a low rate of positive metastasis and no local recurrence in the ipsilateral axillary region. Despite the limited number of cases, these findings suggest the clinical significance of reSNB in IBTR cases.