Background: With greater awareness and increased screening, cancers are increasingly being diagnosed at stage I. Women with these small node-negative tumours have excellent survival prospects after surgery, but many women, especially those with triple-negative and human epidermal growth factor receptor (HER)-2-positive tumours, still receive adjuvant systemic treatments to reduce the recurrence risk.
Aims: We review the outcomes of women diagnosed with stage I (T1N0M0) tumours in our unit and examine the effect of systemic chemotherapy with/without targeted therapy on recurrence patterns and survival outcomes.
Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.
View Article and Find Full Text PDFPost-operative radiotherapy for post-menopausal women with early breast cancer and N1 disease is controversial. Although locoregional control is improved, overall survival (OS) benefit is unclear. The clinical benefit of post-operative irradiation in this group of patients over 10 years was reviewed.
View Article and Find Full Text PDFPurpose: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer.
Methods: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS).
Breast cancer is a prevalent form of cancer worldwide, and the current standard screening method, mammography, often requires invasive biopsy procedures for further assessment. Recent research has explored microRNAs (miRNAs) in circulating blood as potential biomarkers for early breast cancer diagnosis. In this study, we employed a multi-modal spectroscopy approach, combining attenuated total reflection Fourier transform infrared (ATR-FTIR) and surface-enhanced Raman scattering (SERS) to comprehensively characterize the full-spectrum fingerprints of RNA biomarkers in the blood serum of breast cancer patients.
View Article and Find Full Text PDFBreast Cancer Res
November 2023
Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients.
Methods: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion.
The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN.
View Article and Find Full Text PDFBreast cancer is the most prevalent cancer globally. Early detection is crucial and can be achieved by detecting cancer biomarkers in blood, such as circulating miRNAs (microRNAs). In this study, we present a label-free detection method based on broadband multi-resonant infrared metasurface for surface-enhanced infrared absorption (SEIRA) spectroscopy to detect miRNAs.
View Article and Find Full Text PDFCancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG.
View Article and Find Full Text PDFThe robustness of a breast cancer gene signature, the super-proliferation set (SPS), is initially tested and investigated on breast cancer cell lines from the Cancer Cell Line Encyclopaedia (CCLE). Previously, SPS was derived via a meta-analysis of 47 independent breast cancer gene signatures, benchmarked on survival information from clinical data in the NKI dataset. Here, relying on the stability of cell line data and associative prior knowledge, we first demonstrate through Principal Component Analysis (PCA) that SPS prioritizes survival information over secondary subtype information, surpassing both PAM50 and Boruta, an artificial intelligence-based feature-selection algorithm, in this regard.
View Article and Find Full Text PDFXinhui chenpi (XHCP), the sun-dried peel of the mandarin orange, "Chachi," is the most famous crude drug, as well as a traditional seasoning in Chinese cooking. The main cultivation methods of XHCP are cutting and grafting, but it is generally considered that the quality of XHCP after cutting is superior to that obtained from plants propagated by graftings, which had a negative impact on the marketing of the finished product. In our study, a total of 25 samples of XHCP obtained from plants cultivated by either traditional methods (i.
View Article and Find Full Text PDFIdiopathic granulomatous mastitis (IGM) is a rare and benign inflammatory breast disease with ambiguous aetiology. Contrastingly, lactational mastitis (LM) is commonly diagnosed in breastfeeding women. To investigate IGM aetiology, we profiled the microbial flora of pus and skin in patients with IGM and LM.
View Article and Find Full Text PDFBMC Med
August 2022
Background: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilization in a multi-ethnic Asian population.
Methods: This study included 3739 BC patients from the Singapore Breast Cancer Cohort (2010-2018).
Trastuzumab (herceptin) is an effective drug for human epidermal growth factor receptor type 2 (HER2)-positive cancer. However, cardiotoxicity remains a serious complication. In our previous genome-wide association study (GWAS), we identified potential associations for five single nucleotide polymorphisms (SNPs) with trastuzumab-induced cardiotoxicity in a Japanese population.
View Article and Find Full Text PDFRelapse to anti-HER2 monoclonal antibody (mAb) therapies, such as trastuzumab in HER2 breast cancer (BC), is associated with residual disease progression due to resistance to therapy. Here, we identify interferon-γ inducible protein 16 (IFI16)-dependent STING signaling as a significant determinant of trastuzumab responses in HER2 BC. We show that down-regulation of immune-regulated genes (IRG) is specifically associated with poor survival of HER2, but not other BC subtypes.
View Article and Find Full Text PDFThe hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an in vitro culture system modeling human T cell dysfunction and exhaustion in triple-negative breast cancer (TNBC), we find that hypoxia suppresses immune effector gene expression, including in T and NK cells, resulting in immune effector cell dysfunction and resistance to immunotherapy. We demonstrate that hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction.
View Article and Find Full Text PDFObjectives: To evaluate the potential of contrast-enhanced spectral mammography (CESM) in reducing benign breast biopsy rate, thereby improving resource utilization. To explore its potential as a value-adding modality in the management of BI-RADS 4/5 lesions.
Materials And Methods: This was a prospective study conducted between July 2016 and September 2018.
Cancers (Basel)
May 2022
Background: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients.
Methods: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia.
BMC Med
April 2022
Physical activity (PA) is known to reduce breast cancer (BC) risk and improve patient prognosis. However, the association between pre-diagnostic PA and the aggressiveness of BC is unclear. We investigated the associations between PA, BC tumour characteristics, and survival.
View Article and Find Full Text PDFObjectives: Advances in adjuvant therapy have led to increased survival rates after cancer prognosis. Herceptin, a targeted therapy, had first been introduced to Singapore in 2006. We aimed to assess whether subsidies for Herceptin from 2012 will lead to changes in uptake among HER2-positive patients by socioeconomic groups.
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