Breast Cancer最新文献

The immune background of breast cancer is highly heterogeneous and the immune system of the human body plays a dual role by both promoting and suppressing its progression. Innate immune cells are the first line of defense in the immune system and impart protection by identifying and interacting with foreign pathogens and cancer cells. Different innate immune cells like natural killer cells, macrophages, dendritic cells, and myeloid suppressor cells take part in hosting the cancer cells. Autophagy is another key component inside the tumor microenvironment and is linked to the disintegration and recycling of cellular components. Within the tumor microenvironment autophagy is involved with Pattern Recognition Receptors and inflammation. Various clinical studies have shown prominent results where innate immune cells and autophagy in combination are used for pathogen as well as cancer cell clearance. However, it is necessary to comprehend the complex tumor microenvironment so that different therapeutic approaches can be developed to enhance the suppressive actions of the cells toward breast cancer cells. In this review article, the complex interaction between immune cells and breast cancer cells and their role in developing effective immunotherapies to improve patient outcomes are discussed in detail.

Liquid biopsy using circulating tumor DNA (ctDNA) has been reported to be less invasive and effective for comprehensive genetic analysis of heterogeneous solid tumors, including decision-making for therapeutic strategies, predicting recurrence, and detecting genetic factors related to treatment resistance in various types of cancers. Breast cancer, colorectal cancer, and lung cancer are among the most prevalent malignancies worldwide, and clinical studies of liquid biopsy for these cancers are ongoing. Liquid biopsy has been used as a companion diagnostic tool in clinical settings, and research findings have accumulated, especially in cases of colorectal cancer after curative resection and non-small cell lung cancer (NSCLC) after curative chemoradiotherapy, in which ctDNA detection helps predict eligibility for adjuvant chemotherapy. Liquid biopsy using ctDNA shows promise across a wide range of cancer types, including breast cancer, and its clinical applications are expected to expand further through ongoing research. In this article, studies on liquid biopsy in breast cancer, colorectal cancer, and NSCLC are compared focusing on ctDNA.

Background: Assessment of breast volume has a relevance for aesthetic surgery and for the prevention and prediction of breast diseases. This study investigated breast volume measurements using a three-dimensional (3D) body surface scanner integrated in a smartphone device in comparison with magnetic resonance imaging (MRI) scans.

Methods: Breast volume was assessed for 22 women who underwent routine MRI imaging. 3D surface images were acquired using a smartphone's digital texture camera (iPhone 11 Pro Max, Apple, California, USA, 2019). Breast volumes were manually outlined and calculated by two independent investigators using a 3D software tool (Meshmixer 3.5, Autodesk, Inc., 2018). Volume assessments from MRI images were performed by a radiologist using Syngo.via (Siemens Healthcare, Erlangen, Germany, VB50). The agreement between both methods and the inter-observer agreement was calculated with the concordance correlation coefficients and analysed with Bland-Altman plots.

Results: The mean breast volume as determined by MRI volumetry was 771.0 ml on the left side and 763.9 ml on the right side. Utilizing the 3D body surface volume assessment method, the mean breast volume was measured as 660.3 ml (observer A) and 616.8 ml (observer B) on the left side, and 701.9 ml (observer A) and 638.6 ml (observer B) on the right side. Although a high correlation was observed, differences in volume measurements appeared more pronounced in cases of larger breast volume.

Conclusions: Smartphone-based 3D assessment of breast volume sufficiently agreed with MRI-based breast volume. This new technique could be used for cosmetic breast assessments in a surgical context and possibly in breast cancer risk studies assessing breast volume as outcome parameters.

Among the analytes circulating in body fluids, microRNAs, a type of non-coding RNA and known to exist 2655 in primates, have attracted attention as a novel biomarker for cancer screening. MicroRNAs are signaling molecules with important gene expression regulatory functions that can simultaneously control many gene functions and multiple different pathways in living organisms. These microRNAs are transported in extracellular vesicles (EVs), which are lipid bilayers with 50-150 nm in diameter, and are used as communication tools between cells. Furthermore, the EVs that carry these microRNAs circulate in the bloodstream and have other important implications for understanding the pathogenesis and diagnosis of breast cancer. The greatest benefit from cancer screening is the reduction in breast cancer mortality rate through early detection. Other benefits include reduced incidence of breast cancer, improved quality of life, prognosis prediction, contribution to personalized medicine, and relative healthcare cost containment. This paper outlines the latest developments in liquid biopsy for breast cancer, especially focusing on microRNA and EV diagnostics.

Objective: The incidence of venous thromboembolism (VTE) is significantly elevated in breast cancer patients, with a three-to-fourfold increase, and further escalates to sixfold in those undergoing chemotherapy. This study aims to identify the risk factors for VTE and develop a Nomogram risk prediction model distinct from the traditional Khorana score.

Methods: Univariate Cox regression analysis assessed the impact of each variable on the occurrence of VTE, while stepwise multivariate Cox regression analysis identified independent predictors. Based on these results, we constructed a Nomogram model. The model's performance was validated using the C-index, receiver-operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Comparisons were made with the Khorana score to evaluate the practical application value.

Results: Out of the 903 patients, 108 (11.96%) developed VTE. Cox regression analysis identified that Stage, undergoing surgery, age, white blood cells (WBC), D-dimer, and carcinoembryonic antigen (CEA) were significant risk factors for VTE (P < 0.05). The Nomogram model's C-index was 0.77 (95% CI 0.72-0.83) in the training set and 0.76 (95% CI 0.69-0.84) in the validation set. The model demonstrated excellent predictive accuracy and generalizability on the receiver-operating characteristic (ROC) curves and calibration curves. Compared to the traditional Khorana score, the Nomogram model showed superior predictive accuracy and greater clinical benefit.

Conclusions: This study established a VTE risk prediction model for breast cancer patients undergoing chemotherapy. The model is characterized by its intuitive and straightforward application, making it highly suitable for rapid VTE risk assessment in clinical practice.

Background: In CAPItello-291, capivasertib-fulvestrant significantly improved progression-free survival (PFS) versus placebo-fulvestrant in the overall and PIK3CA/AKT1/PTEN-altered population with hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. Capivasertib-fulvestrant is approved in Japan for the treatment of patients with one or more tumor biomarker alterations (PIK3CA, AKT1 or PTEN). Here, we report outcomes in the CAPItello-291 subgroup of patients from Japan.

Methods: Adults with HR-positive/HER2-negative advanced breast cancer whose disease had relapsed or progressed during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy, were randomly assigned (1:1 ratio) to receive capivasertib or placebo, plus fulvestrant. The dual primary endpoint was investigator-assessed PFS in the overall and PIK3CA/AKT1/PTEN-altered population. Safety was a secondary endpoint.

Results: Of 708 patients randomized in CAPItello-291, 78 were from Japan (37 randomized to capivasertib-fulvestrant and 41 to placebo-fulvestrant). In the Japan subgroup, PFS numerically favored the capivasertib-fulvestrant arm (hazard ratio 0.73; 95% CI 0.40-1.28), consistent with the analysis of PFS in the global population. Similarly, in the Japan subgroup of patients with PIK3CA/AKT1/PTEN-altered tumors, PFS favored the capivasertib-fulvestrant arm (hazard ratio 0.65; 95% CI 0.29-1.39), consistent with the global population. The adverse event profile of capivasertib-fulvestrant in the Japan subgroup was broadly similar to that in the global population; no new safety concerns were identified.

Conclusion: Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen.

Background: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer.

Methods: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models.

Results: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases.

Conclusion: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

Background: Identifying whether there is residual carcinoma in remaining suspicious calcifications after neoadjuvant chemotherapy (NAC) in breast cancer patients can provide crucial information for surgeons in determining the most appropriate surgical approach. Therefore, we investigated factors predicting calcifications without residual carcinoma (ypCalc_0) or with residual carcinoma (ypCalc_ca) and aimed to develop a prediction model for patients exhibiting residual suspicious calcifications on mammography but complete response on MRI after NAC.

Methods: This retrospective study included breast cancer patients undergoing NAC, showing residual suspicious mammographic calcifications but complete response on MRI between January 2019 and December 2020 (development set) and between January 2021 and December 2022 (validation set). Multivariable logistic regression analysis identified significant factors associated with ypCalc_0. The prediction model, developed using a decision tree and factors from logistic regression analysis, was validated in the validation set.

Results: The development set included 134 women (mean age, 50.6 years; 91 with ypCalc_0 and 43 with ypCalc_ca) and validation set included 146 women (mean age, 51.0 years; 108 with ypCalc_0 and 38 with ypCalc_ca). Molecular subtype (P = .0002) and high Ki-67 (P = .02) emerged as significant independent factors associated with ypCalc_0 in the development set. The prediction model, incorporating hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ with high Ki-67 as ypCalc_0 predictors, and HR+/HER2- cancers or HR+/HER2+ or triple-negative (TN) cancers with low Ki-67, as ypCalc_ca predictors, achieved an area under receiver operating characteristic curve of 0.844 (95% CI 0.774-0.914) in the validation set.

Conclusion: Minimized surgery may be considered for managing residual calcifications in HR-/HER2+ with high Ki-67 cancers, while complete excision is recommended for HR+/HER2- breast cancers or for HR+/HER2+or TN breast cancers with low Ki-67.

Circulating tumor cells (CTCs) are tumor cells that shed from the primary tumor or metastatic loci, intravasate, and circulate in the bloodstream. CTCs have been suggested to play a major role in the metastatic spread of cancer, constantly shedding from tumors during proliferation or as a result of mechanical insults. Breast cancer (BC) is one of the most representative tumors in CTC research, with several studies conducted on its clinical validity and utility in both early and advanced BC (EBC and ABC, respectively). The assessment of the number and molecular profiles of CTCs is expected to provide a more tailored therapy for patients with BC. The detection of CTCs is usually dependent on molecular markers, and epithelial cell adhesion molecules are widely used. Although the CellSearch^® technology has been widely utilized for CTC detection, recent advances have led to the development of novel detection methods, facilitating further molecular analysis. In this review, we discuss the clinical applications of CTCs, current status of research, and efforts to incorporate CTC analysis into clinical practice. Additionally, we discuss potential challenges and future directions for integrating CTC analysis into clinical practice.

Background: Breast cancer treatment prioritizes molecular subtypes over histologic types. However, considering the unique biological behavior of invasive lobular carcinoma (ILC), its diagnosis is crucial for patient management. Therefore, this study aimed to review breast cancer cases, focusing on the E-cadherin patterns and lobular morphology of cases misclassified in the original reports.

Methods: A comprehensive review was conducted on 481 breast cancer biopsy cases diagnosed as invasive breast carcinoma of no special type (IBC-NST) or ILC with E-cadherin staining. These cases were categorized into six groups based on tumor morphology (ductal/lobular) and E-cadherin expression pattern (membranous/loss/aberrant): (1) ductal/membranous, (2) lobular/loss, (3) lobular/aberrant, (4) mixed, (5) ductal/loss or aberrant, and (6) lobular/membranous.

Results: In 211 cases (43.8%), an E-cadherin pattern indicating ILC (loss and aberrant) was observed alongside lobular morphology, representing 5.52% of all breast cancer biopsies during the relevant period. Moreover, 181 cases (37.6%) showed a membranous pattern with ductal morphology, 4 (0.8%) were mixed IBC-NST and ILC, and 85 (17.7%) exhibited discordance between morphology and E-cadherin expression. Notably, only 25.9% (15/58) of cases in group 3, characterized by aberrant E-cadherin patterns, were initially diagnosed as ILC, highlighting a significant diagnostic discrepancy. In group 6, where membranous E-cadherin pattern was present with lobular morphology, only 3.4% (2/58) were diagnosed as ILC in the original reports, indicating diagnostic challenges in morphology and immunohistochemistry discordance. Similarly, in group 5, which had ductal morphology with loss or aberrant E-cadherin expression, the initial diagnosis rate of IBC-NST was 33.3% (9/27), reflecting the complexities in interpreting discordant cases.

Conclusions: In real-world practice, diagnosing ILC often heavily depends on E-cadherin results. This study emphasizes the need for diagnostic clarification in cases with discordance between morphology and E-cadherin patterns.