Breast Cancer最新文献

Background: To analyze in a prospective study the long-term safety and efficacy of 3-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) for Japanese women with early breast cancer.

Methods: Breast cancer patients with pathological tumor size ≤ 3 cm, age ≥ 20 years, lumpectomy with at least a 5 mm margin, and ≤ 3 positive axillary nodes were eligible. APBI was delivered by 3D-CRT at a dose of 38.5 Gy in 10 fractions over 10 days. The primary endpoints were the frequency and severity of acute and late radiation toxicities, and secondary endpoints were local control, survival, and cosmesis. The sample size was determined based on the incidence of ≥ grade 3 acute and late radiation toxicities, which required 71 enrollments.

Results: Between 2008 and 2010, 73 patients enrolled in this trial. Twelve patients (16%) had 1-3 lymph node metastases. At a median follow-up of 12.6 years (range: 2.7-13.9 years), there were no cases of grade ≥ 3 acute or late toxicity. There were 4 ipsilateral breast tumor recurrence (IBTR) events: 12-year IBTR incidence was 4.4%. The difference in the incidence of IBTR between node-negative and node-positive patients was marginal (1.9% vs. 16.7%, p = 0.055). The majority of patients (94.4% at 2 years, 89.3% at 10 years after enrollment) had excellent/good cosmesis.

Conclusions: APBI delivered with 3D-CRT is a feasible treatment option for Asian females, but it was indicated that node-positive status might increase IBTR risk.

Background: Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients.

Methods: Between July 2016 and January 2022, a total of 268 patients were eligible for analysis. The endpoints included in-field and out-field cervical failures, local-regional recurrence-free survival (LRRFS), SCV recurrence-free survival (SRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS).

Results: During a median follow-up of 37 months (range 3-89 months), 17 patients (6.3%) developed local-regional recurrence as the first recurrence event, with 13 having concomitant distant-metastasis (DM); 56 patients (20.9%) had DM alone. The 3-year rates of LRRFS, SRF, DMFS, RFS, and OS were 92.3%, 94.5%, 74.5%, 73.0%, and 90.0%, respectively. 89.2% of patients received RT with the cranial border at the top of hyoid bone, and 95.1% of patients received a boost not exceeding the level of cricoid cartilage. A total of 11 patients (4.1%) developed ipsilateral SCV failure, and 3 patients (1.1%) experienced cervical failure, including 2 in-field failures and 1 out-field failure. Neoadjuvant systemic therapy (NST) was administered to 234 patients (87.3%). In the multivariate analysis, non-ypN0, triple-negative subtype and cT4 at diagnosis were predictors of worse SRFS and RFS in NST subgroup.

Conclusion: Our findings suggest that radical RT with cranial border of irradiation field at the hyoid bone level lead to excellent local-regional control, and out-field cervical failure was rare. The irradiation field might not extend to mastoid process.

Background: Cryoablation is currently being investigated as a minimally invasive alternative to breast-conserving surgery. This meta-analysis investigates the local recurrence and residual tumor rates after cryoablation for small early-stage breast cancers.

Methods: A systematic search was conducted on Embase, PubMed, Google Scholar, and the International Clinical Trials Registry Platform from inception to 16 June 2024. Studies of patients with breast cancers ≤ 20 mm treated with cryoablation only or cryoablation followed by surgery were included. Pooled local recurrence rates (cryoablation only) and pooled residual tumors rates (cryoablation followed by surgery) were estimated with mixed-effects models. Between-study heterogeneity was assessed using I² statistics. Where I² exceeded 50%, outlier and influence analysis, followed by sensitivity analysis excluding outliers, were conducted.

Results: Twelve studies met inclusion criteria, of which 7 studies (530 female patients, 531 breast tumors) reported on patients treated with cryoablation only and 5 studies (220 female patients, 222 breast tumors) reported on patients treated with cryoablation followed by surgery. For studies on cryoablation only, pooled local recurrence rate was 1.1% (95% CI 0.42-3.03%) with low between-study heterogeneity (I² value = 0%; 95% CI 0.0-70.8%; p = 0.95). For studies on cryoablation followed by surgery, pooled residual tumor rate was 12.0% (95% CI 3.85-31.64%); however, substantial between-study heterogeneity (I² value = 76.1%; 95% CI 41.7-90.2%; p < 0.01) was present. Influence analysis revealed 1 outlier study. When this study was excluded, pooled residual tumor rate was 8.2% (95% CI 3.84-16.68%) with improvement in heterogeneity (I² value = 0%; 95% CI 0.0-84.7%; p = 0.64).

Conclusion: Pooled local recurrence and residual tumor rates after cryoablation are comparable to local recurrence rates after breast-conserving therapy and re-excision rates following breast-conserving surgery, respectively. These results are encouraging but should be interpreted with caution due to lack of comparative studies.

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.

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.

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.

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.

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: 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.

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.