Evaluation of Targeted Alpha Therapy Using [At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models.

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion.

Prognostic value of serum tartrate‑resistant acid phosphatase‑5b for bone metastasis in patients with resectable breast cancer.

Bone metastasis significantly affects the quality of life of patients with metastatic breast cancer, and can shorten overall survival. Identifying patients with early-stage breast cancer at high risk for bone metastasis and preventing bone metastasis may lead to a better quality of life and prolonged survival. The present study investigated whether serum tartrate-resistant acid phosphatase-5b (TRACP-5b), a bone turnover marker, can be a prognostic factor for bone metastasis.

High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer.

Purpose: Breast cancer tumors frequently have intratumoral heterogeneity (ITH). Tumors with high ITH cause therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to a poor prognosis for HER2-targeted adjuvant therapy resistance in primary breast cancers.

Evaluation of methylation in the lysate of sentinel lymph nodes for detecting breast cancer metastasis: A diagnostic accuracy study.

The restriction enzyme-based digital methylation-specific polymerase chain reaction (RE-dMSP) assay is useful for diagnosing sentinel lymph node (SN) metastasis in patients with breast cancer, by detecting tumor-derived methylated Ras association domain-containing protein 1 (RASSF1A). In addition, this assay has high concordance (95.0%) with one-step nucleic acid amplification (OSNA).

Hypercalcemia affected in metastatic breast cancer patients without bone metastasis: report of three cases.

Background: Since humoral hypercalcemia of malignancy (HHM) in breast cancer patients without bone metastasis is rare, the clinical features of this condition are not fully understood.

Case Presentation: During the recent 12 years, 3602 patients were diagnosed with breast cancer in our institution, and only three patients developed HHM without bone metastasis. They were all recurrent breast cancer patients with visceral metastases including the lung and the liver.

Comparison of "click-to-sense" assay with frozen section analysis using simulated surgical margins in breast cancer patients.

Purpose: We have shown that "Click-to-sense" (CTS) assay based on the visualization of cancer cells by fluorescence probe targeted for acrolein is useful for differentiating between the malignant and benign lesions of the breast. In the present study, we aimed to apply CTS assay to the examination of the simulated surgical margins, being compared with frozen section (FS) analysis.

Experimental Design: The simulated surgical margin samples (n = 300) were obtained from 1 to 2 cm distant sites from the tumor margin in the mastectomy specimens of breast cancer patients, and divided into the training (n = 150) and validation (n = 150) set.

A case of sternal osteomyelitis during treatment with everolimus for recurrent breast cancer.

Background: Everolimus is a mechanistic-target-of-rapamycin (mTOR) inhibitor bearing a potent antitumor effect against hormone receptor-positive breast cancer. Here, we report the case of a patient with recurrent breast cancer who developed osteomyelitis during the treatment with everolimus plus exemestane.

Case Presentation: A 56-year-old woman with early-stage breast cancer underwent right mastectomy and axillary lymph node dissection at the age of 45.

Comparison of the multigene panel test and OncoScan™ for the determination of amplification in breast cancer.

The diagnostic accuracy of the multigene panel test (MPT) and OncoScan™ in the determination of amplification in breast tumors remains controversial. In the present study, copy number was analyzed using both MPT and OncoScan™ in 45 breast tumors and was compared with that in fluorescent hybridization (FISH) analysis. Tumors with low cellularity were examined using tumor cell enrichment and fluorescence‑activated cell sorting.

Aesthetic utility of addition of nipple-areola recentralization to rotation flap according to nipple tumor distance for patients with lower-outer or upper-inner located breast cancers.

We aimed to validate the cosmetic utility of addition of nipple-areola recentralization (NAR) to rotation flap according to nipple tumor distance (NTD) as a volume displacement technique after breast conserving surgery (BCS) for lower-outer and upper-inner breast cancers. Twenty breast cancer patients who had been treated with rotation flap with (Group 1; n = 6) or without (Group 2; n = 14) NAR after BCS for lower-outer or upper-inner located tumors, and those who had undergone BCS without oncoplastic surgical technique for tumors in the same area (Control group; n = 43), were retrospectively investigated. Cosmetic outcome was evaluated using Harvard scale and/or BCCT.

Prediction of pathological complete response after neoadjuvant chemotherapy in breast cancer: comparison of diagnostic performances of dedicated breast PET, whole-body PET, and dynamic contrast-enhanced MRI.

Purpose: To compare the diagnostic performance of ring-type dedicated breast PET (dbPET), whole-body PET (WBPET), and DCE-MRI for predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC).

Methods: This prospective study included 29 women with histologically proven breast cancer on needle biopsy between July 2016 and July 2019 (age: mean 55 years; range 35-78). Patients underwent WBPET followed by ring-type dbPET and DCE-MRI pre- and post-NAC for preoperative evaluation.

Impact of tumor cellularity on the HER2 amplification assay by OncoScan™ in breast cancer.

HER2 amplification is seen in 20-25% of primary breast cancer cases, and HER2 detection is performed routinely in primary operable, as well as metastatic breast cancer patients. Currently, HER2 is the only gene of which amplification is routinely assayed by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC). However, histochemical assay (FISH/IHC) of multiple target genes is laborious and time-consuming, and simultaneous amplification by microarray is preferred.

Enhanced humoral immunity in breast cancer patients with high serum concentration of anti-HER2 autoantibody.

Humoral immunity plays a substantial role in the suppression of breast cancer. We have revealed that a high serum concentration of anti-HER2 autoantibody (HER2-AAb) is associated with favorable outcomes in patients with invasive breast cancer. Thus, we aimed to clarify the association between high serum concentration of HER2-AAb and humoral immune response in the tumor microenvironment.

Sentinel lymph node biopsy after introducing Twirl® breast markers into suspicious lymph nodes in breast cancer patients.

Ten stage I/II breast cancer patients with one or two suspicious lymph nodes (LNs) detected on ultrasonography underwent sentinel LN biopsy (SLNB) after the introduction of Twirl® breast markers into each suspicious LN revealed that each Twirl®-marked LN was SLN and was likely the first SLN. Three patients had less than three SLN metastases and were candidates for sparing completion axillary lymph node dissection (cALND). Indeed, of them, one underwent breast-conserving surgery without cALND and the other two underwent total mastectomy with cALND.

Determining homologous recombination deficiency scores with whole exome sequencing and their association with responses to neoadjuvant chemotherapy in breast cancer.

Recent studies demonstrated that homologous repair deficiency (HRD) score is a useful marker for response to poly (ADP-ribose) polymerase inhibitors or platinum-based chemotherapy. We determined HRD scores and elucidated the clinicopathologic characteristics of HRD-high tumors and their response to non-platinum-based chemotherapy. Primary breast cancer patients (n = 120) were pre-operatively treated with paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC).

Effect of Computer-aided Detection System Use on the Duration of MRI-guided Biopsy of the Breast.

Background/aim: Magnetic resonance imaging (MRI)-guided breast biopsy is a complex and time-consuming procedure. This study aimed to clarify the factors that affect the duration of the procedure.

Patients And Methods: Twenty-eight examinations performed at our institute for 27 lesions detected solely on MRI were analyzed.

Development of Prediction Model Including MicroRNA Expression for Sentinel Lymph Node Metastasis in ER-Positive and HER2-Negative Breast Cancer.

Background: The aim of our study is to find microRNAs (miRNAs) associated with sentinel lymph node metastasis (SLNM) and to develop a prediction model for SLNM in ER-positive and HER2-negative (ER+/HER2-) breast cancer.

Patients And Methods: In the present study, only ER+/HER2- primary breast cancer was considered. The discovery set for SLNM-associated miRNAs included 10 tumors with and 10 tumors without SLNM.

Detection of ctDNA with Personalized Molecular Barcode NGS and Its Clinical Significance in Patients with Early Breast Cancer.

We attempted to detect circulating tumor DNA (ctDNA), taking advantage of molecular barcode next-generation sequencing (MB-NGS), which can be more easily customized to detect a variety of mutations with a high sensitivity than PCR-based methods. Sequencing with a gene panel consisting of the 13 most frequently mutated genes in breast tumors from stage I or II patients revealed 95 somatic mutations in the 12 genes in 62% (62/100) of tumors. Then, plasma DNA from each patient (n = 62) before surgery was analyzed via MB-NGS customized to each somatic mutation, resulting in the detection of ctDNA in 16.

Emerging Technologies for Real-Time Intraoperative Margin Assessment in Future Breast-Conserving Surgery.

Clean surgical margins in breast-conserving surgery (BCS) are essential for preventing recurrence. Intraoperative pathologic diagnostic methods, such as frozen section analysis and imprint cytology, have been recognized as crucial tools in BCS. However, the complexity and time-consuming nature of these pathologic procedures still inhibit their broader applicability worldwide.

Molecular Barcode Sequencing of the Whole Ligand Binding Domain of the ESR1 Gene in Cell-Free DNA from Patients with Metastatic Breast Cancer.

ESR1 mutations in breast cancer are known as one of the mechanisms of resistance to aromatase inhibitors. These mutations often occur in the hotspot regions in the ligand binding domain (LBD), but comprehensive mutational analysis has shown that mutations are observed throughout the whole LBD. We previously developed a molecular barcode sequencing (MB-NGS) technique to detect ESR1 hotspot mutations in plasma with high sensitivity.

Hookwire-guided Sentinel Lymph Node Biopsy Using Contrast-enhanced Ultrasonography Followed by a One-step Nucleic Acid Amplification (OSNA) Assay for Breast Cancer.

Aim: To investigate the feasibility of hookwire-guided sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasonography (CEUS) followed by a one-step nucleic acid amplification (OSNA) assay.

Patients And Methods: Clinical T1-2N0M0 breast cancer patients scheduled to undergo SLNB participated in this study. Both Sonazoid® and dye were used as tracers, and the most upstream sentinel lymph node (SLN) at each lymphatic flow detected by CEUS (First-SLN) was sampled under hookwire guidance, a procedure called "Sona-Hook".

Development of recurrence risk score using 95‑gene classifier and its application to formalin‑fixed paraffin‑embedded tissues in ER‑positive, HER2‑negative and node‑negative breast cancer.

We previously developed a 95‑gene classifier (95GC) to classify ER‑positive/HER2‑negative/node‑negative (ER+/HER2‑/N0) breast cancer as high‑ and low‑risk. The present study aimed to devise a 95GC recurrence score (95GCRS) to estimate recurrence risk more precisely and, although the 95GC was originally developed using fresh‑frozen (FF) tissues, this was applied to formalin‑fixed paraffin‑embedded (FFPE) tissues. 95GCRS was calculated using between‑group analysis and denominated as a value from 0 to 100.

Highly sensitive detection of sentinel lymph node metastasis of breast cancer by digital PCR for RASSF1A methylation.

One‑step nucleic acid amplification (OSNA) targeting cytokeratin 19 (CK19) mRNA expression and pathological examination are widely used for the intraoperative diagnosis of sentinel node (SN) metastasis. The aim of the present study was to develop a novel assay for detecting SN metastasis by targeting Ras association domain‑containing protein 1 (RASSF1A) methylation in tumor cells, and to compare its performance with OSNA. Using digital PCR with methylation‑specific restriction enzymes (RE‑dMSP), our assay was able to detect ≥3 copies of methylated DNA per well, and was ≥10 times more sensitive than real‑time PCR with bisulfite modification.