Background: Patients with triple negative breast cancer (TNBC) who have a poor response to neoadjuvant chemotherapy (NAC) have worse survival and new treatment strategies need to be developed. TNBC is considered a subtype in which the cyclic GMP-AMP synthase (cGAS) is linked to the stimulator of interferon genes (STING) pathway, an innate immune response that recognizes cytosolic nucleic acid components, is activated when DNA damage occurs, and is attracting attention as a new therapeutic target.
Methods: Patients with TNBC who underwent surgery following NAC and for whom pre- and post-treatment tissue specimens were available were enrolled in this study.
Breast Cancer Res Treat
February 2025
Metastasis is a complex process that remains poorly understood at the molecular levels. We profiled single-cell transcriptomic, genomic, and epigenomic changes associated with cancer cell progression, chemotherapy resistance, and metastasis from a Stage IV breast cancer patient. Pretreatment- and posttreatment-specimens from the primary tumor and distant metastases were collected for single-cell RNA sequencing and subsequent cell clustering, copy number variation (CNV) estimation, transcriptomic factor estimation, and pseudotime analyses.
View Article and Find Full Text PDFCellular senescence and senescence-associated secretory phenotype (SASP) in stromal cells within the tumor microenvironment promote cancer progression. Although cellular senescence has been shown to induce changes in the higher-order chromatin structure and abnormal transcription of repetitive elements in the genome, the functional significance of these changes is unclear. In this study, we examined the human satellite II (hSATII) loci in the pericentromere to understand these changes and their functional significance.
View Article and Find Full Text PDFBackground: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.
Methods: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021.
Background: The intratumor heterogeneity (ITH) of cancer cells plays an important role in breast cancer resistance and recurrence. To develop better therapeutic strategies, it is necessary to understand the molecular mechanisms underlying ITH and their functional significance. Patient-derived organoids (PDOs) have recently been utilized in cancer research.
View Article and Find Full Text PDFBackground: Oestrogen receptor (ER) signalling-dependent cancer cell growth is one of the major features of ER-positive breast cancer (BC). Inhibition of ER function is a standard and effective treatment for ER-positive tumours; however, ~20% of patients with ER-positive BC experience early or late recurrence. In this study, we examined intertumour heterogeneity from an epigenetic perspective based on the hypothesis that the intrinsic difference in epigenetic states around ER signalling pathway underlies endocrine therapy resistance.
View Article and Find Full Text PDFBreast Cancer Res Treat
November 2022
Purpose: This study investigated the clinical impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) on survival in patients with oligometastatic breast cancer.
Patients And Methods: We collected data from 397 patients who underwent primary breast surgery from 2004 to 2015 and developed recurrence during the follow-up. We reviewed the images and clinical information and defined OMD according to the European Society for Medical Oncology advanced breast cancer guidelines.
In breast cancer patients, tumor heterogeneity is associated with prognosis and therapeutic response; however, the epigenetic diversity that exists in primary tumors remains unknown. Using a single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq), we obtained the chromatin accessibility profiles of 12,452 cells from 16 breast cancer patients including 11 luminal, 1 luminal-HER2, 1 HER2, and 3 triple-negative subtypes. Via this profiling process, tumors were classified into cancer cells and the tumor microenvironment, highlighting the heterogeneity of disease-related pathways including estrogen receptor (ER) signaling.
View Article and Find Full Text PDFThe recurrence risk of estrogen receptor (ER)-positive breast cancer remains high for a long period of time, unlike other types of cancer. Late recurrence reflects the ability of cancer cells to remain dormant through various events, including cancer stemness acquisition, but the detailed mechanism is unknown. ESR1 locus enhancing and activating noncoding RNAs (ELEANORS) are a cluster of nuclear noncoding RNAs originally identified in a recurrent breast cancer cell model.
View Article and Find Full Text PDFAnaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis.
View Article and Find Full Text PDFExpert Rev Anticancer Ther
September 2021
The use of sentinel node biopsy (SNB) following neoadjuvant chemotherapy (NAC) for patients with cN1 breast cancer is controversial. Improvements of negative predictive value (NPV) by axillary ultrasound (AUS), which corresponds to the accurate prediction rate of node-negative status after NAC, would lead to decreased FNR of SNB following NAC. In this study, we retrospectively investigated the accurate prediction rate of NPV by AUS after NAC in patients with cytologically node-positive breast cancer treated between January 2012 and December 2016.
View Article and Find Full Text PDFMyofibroblastoma is a rare benign mesenchymal tumor typically arising in the breast. We report a diagnostically challenging case of myofibroblastoma of the breast showing a rare palisaded morphology and an uncommon desmin- and CD34-negative immunophenotype. A 73-year-old man underwent an excision for an 8 mm-sized breast mass.
View Article and Find Full Text PDFBackground: Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of an in situ carcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked an in situ component of primary carcinoma.
View Article and Find Full Text PDFGenes involved in the homologous recombination repair pathway-as exemplified by BRCA1, BRCA2, PALB2, ATM, and CHEK2-are frequently associated with hereditary breast and ovarian cancer syndrome. Germline mutations in the loci of these genes with loss of heterozygosity or additional somatic truncation at the WT allele lead to the development of breast cancers with characteristic clinicopathological features and prominent genomic features of homologous recombination deficiency, otherwise referred to as "BRCAness." Although clinical genetic testing for these and other genes has increased the chances of identifying pathogenic variants, there has also been an increase in the prevalence of variants of uncertain significance, which poses a challenge to patient care because of the difficulties associated with making further clinical decisions.
View Article and Find Full Text PDFThe magnitude and scope of intrinsic age-correlated and host endocrine age-correlated gene expression in breast cancer is not well understood. From age-correlated gene expression in 3,071 breast cancer transcriptomes and epithelial protein expression of 42 markers in 5,001 breast cancers and 537 normal breast tissues, we identified a majority of age-correlated genes as putatively regulated by age-dependent estrogen signaling. Surprisingly, these included genes encoding the chromatin modifier EZH2 (which had a negative age correlation) and associated H3K27me3 (which had an inverse, positive age correlation).
View Article and Find Full Text PDFMany patients with positive margins following breast-conserving surgery (BCS) undergo re-excisions that aim to remove residual disease from the breast, which brings a tremendous emotional burden in addition to financial consequences. We sought to determine whether re-excisions could be safely avoided without compromising local control and survival by using whole-breast radiation therapy (WBRT) with a tumor bed boost in patients with early-stage breast cancer with focally positive, tumor-exposed margins after BCS. All patients with ductal carcinoma in situ (DCIS) and/or invasive breast cancer (IBC) who had pathologically tumor-exposed margins following BCS, without re-excision and treated with WBRT with tumor bed boost between March 2005 and December 2011, were included.
View Article and Find Full Text PDFGiant cell tumors of soft tissue (GCT-ST) arising in the breast are extremely rare. We report a unique case of breast GCT-ST coincident with ductal carcinoma in situ (DCIS), diagnosed with histological, immunohistochemical, and H3F3A (Histone H3.3) mutation analyses.
View Article and Find Full Text PDFBackground: The double-tracer method has been established for sentinel node (SN) mapping in gastric cancer surgery. However, there remain several unresolved issues that prevent its widespread use in clinical practice. In this study, we aimed to demonstrate the feasibility of single-tracer SN mapping in laparoscopic surgery for gastric cancer, using indocyanine green (ICG) fluorescence imaging with a one-step nucleic acid amplification (OSNA) assay intraoperatively.
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