and/or Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer.

Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis.

Granzyme B Expression in the Tumor Microenvironment as a Prognostic Biomarker for Patients with Triple-Negative Breast Cancer.

Tumor-infiltrating lymphocytes in the tumor microenvironment are important in the treatment of triple-negative breast cancer (TNBC). Cytotoxic T cells produce cytokines and cytotoxic factors, such as perforin and granzyme, which induce apoptosis by damaging target cells. To identify biomarkers of these cells, we investigated granzyme B (GZMB) in the tumor microenvironment as a biomarker of treatment response and prognosis in 230 patients with primary TNBC who underwent surgery without preoperative chemotherapy between January 2004 and December 2014.

A novel germline mutation of TP53 with breast cancer diagnosed as Li-Fraumeni syndrome.

TP53 is a tumor suppressor gene and, when dysfunctional, it is known to be involved in the development of cancers. Li-Fraumeni syndrome (LFS) is a hereditary tumor with autosomal dominant inheritance that develops in people with germline pathogenic variants of TP53. LFS frequently develops in parallel to tumors, including breast cancer.

CCND1 Copy Number Variation in Circulating Tumor DNA from Luminal B Breast Cancer Patients.

Background/aim: Abnormalities in the cyclin D1-CDK4/6 complex have been implicated in breast cancer proliferation and resistance to treatment. Recently, new drugs have been developed to target CDK4/6. Meanwhile, liquid biopsy has received great interest in oncology.

Significance of the Multi-gene Panel myRisk in Japan.

Background/aim: Hereditary tumors are estimated to account for approximately 5-10% of all tumors. In Europe and the United States, multi-gene panel testing (MGPT) is the standard method used for identifying potential causative genes. However, MGPT it is still not widely used in Japan.

Genetic medicine is accelerating in Japan.

Background: In 2018, BRACAnalysis® was covered by medical insurance in Japan as a companion diagnostic test for the poly ADP-ribose polymerase inhibitor olaparib. In April 2020, eligibility for BRCA1/2 genetic testing was expanded to the diagnosis of hereditary breast and ovarian cancer syndrome, and medical management including prophylactic surgery and surveillance were covered by public insurance for BRCA1/2 mutation carriers who developed breast or ovarian cancer. The amount of BRCA1/2 genetic testing has been increasing recently, but the number of subjects and the impact of testing for patients' outcomes remain unclear.

Current Status and Problems of Breast Cancer Treatment with Schizophrenia.

Background: Schizophrenia is a devastating mental disease that affects approximately 1% of the world's population. Breast cancer is the second most common type of cancer in the world that causes death in women. It is often unclear whether patients with schizophrenia receive recommended cancer treatment that met the guideline.

Effect of the 2013 ASCO-CAP HER2 Testing Guideline on the Management of IHC/HER2 2+ Invasive Breast Cancer.

Background/aim: With advances in anti-HER2 treatment and improved prognoses of HER2-positive breast cancer, the American Society of Clinical Oncology and the American Society of Pathologists (ASCO/CAP) have revised the HER2 diagnostic guidelines several times. We examined how to respond clinically to the revisions of the interpretation of the immunohistochemistry (IHC) method.

Patients And Methods: We re-evaluated 254 patients diagnosed as HER2 IHC equivocal, who underwent fluorescence in situ hybridization (FISH) before and after the IHC diagnostic criteria update in 2013.

Neoantigens elicit T cell responses in breast cancer.

Neoantigens are tumour-specific antigens that arise from non-synonymous mutations in tumour cells. However, their effect on immune responses in the tumour microenvironment remains unclear in breast cancer. We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction from non-synonymous single nucleotide variants (nsSNVs) among exonic mutations.

Validity of the prognostication tool PREDICT version 2.2 in Japanese breast cancer patients.

Introduction: PREDICT is a prognostication tool that calculates the potential benefit of various postsurgical treatments on the overall survival (OS) of patients with nonmetastatic invasive breast cancer. Once patient, tumor, and treatment details have been entered, the tool will show the estimated 5-, 10-, and 15-year OS outcomes, both with and without adjuvant therapies. This study aimed to conduct an external validation of the prognostication tool PREDICT version 2.

Surgical treatment for breast cancer in a patient with erythropoietic protoporphyria and photosensitivity: a case report.

Background: Erythropoietic protoporphyria (EPP) is a rare disorder of heme synthesis. Patients with EPP mainly show symptoms of photosensitivity, but approximately 20% of EPPs are associated with the liver-related complications. We report a case of breast cancer in a 48-year-old female patient with EPP in whom meticulous perioperative management was required in order to avoid complications resulting from this disease.

Breast metastasis from pelvic high-grade serous adenocarcinoma: a report of two cases.

Background: Metastatic tumors to the breast reportedly account for 0.5% to 2.0% of all malignant breast diseases.

Comprehensive molecular profiling broadens treatment options for breast cancer patients.

Precision oncology with next generation sequencing (NGS) using tumor tissue with or without blood has begun in Japan. Tumor molecular profiling tests are available, including the OncoGuide™ NCC Oncopanel System and FoundationOne CDx (F1CDx). Our purpose was to identify potentially actionable genetic alterations in breast cancer with this comprehensive tumor profiling test.

Microsatellite instability in Japanese female patients with triple-negative breast cancer.

Background: It is important to identify biomarkers for triple-negative breast cancers (TNBCs). Recently, pembrolizumab, an immune checkpoint inhibitor (ICI) for programmed cell death 1 (PD-1), was approved as a treatment strategy for unresectable or metastatic tumor with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency, such as malignant melanoma, non-small cell lung cancer, renal cell cancer and urothelial cancer. In addition, results from clinical trials suggested that ICI was a promising treatment for TNBCs with accumulated mutations.

T-bet lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer.

Purpose: T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells.

Methods: This study included 242 patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014.

[Significance of Endocrine Therapy for Unresected Primary Breast Cancer].

At present, surgery is still the recommended principal treatment for breast cancer. However, there are conditions in which surgery is not suitable, for example in elderly or high-risk patients and those who do not wish to undergo the procedure. This study presents a case series of 8 patients with unresected breast cancer who were administered hormonal therapy as an optional treatment.

QOL-enhancing surgery for patients with HER2-positive metastatic breast cancer.

The role of the resection of primary tumour in stage IV breast cancer is unclear. Systemic therapy is recommended to prolong the survival and improve the quality of life (QOL). However, even if the systemic therapy is effective to control distant metastasis, sometimes the local lesion worsens, especially in the aggressive subtypes such as HER2-positive breast cancer.

Efficacy and Safety of Bi-weekly Pegfilgrastim for Dose-dense Chemotherapy-induced Neutropenia in Breast Cancer Patients.

Background/aim: The dose-dense doxorubicin and cyclophosphamide (ddAC) for patients with HER-2-negative breast cancer is recommended by the National Comprehensive Cancer Network guideline in US. However, there are little data on serum G-CSF concentrations in patients undergoing bi-weekly dose-dense therapy with pegfilgrastim. The objective of this study was to compare the serum G-CSF concentrations in patients receiving pegfilgrastim in bi- or tri-weekly regimens.

Catumaxomab with Activated T-cells Efficiently Lyses Chemoresistant EpCAM-positive Triple-negative Breast Cancer Cell Lines.

Background/aim: Epithelial cell adhesion molecule (EpCAM) is expressed in various types of cancer, including breast cancer, and is correlated with metastasis, invasion, therapeutic resistance and prognosis. Moreover, several cell surface markers, such as CD44 and EpCAM, are molecular targets on cancer stem-like cells of breast cancer. The aim of this study was to investigate whether catumaxomab, a clinical-grade bispecific antibody that binds to both EpCAM on tumor cells and CD3 on T-cells, combined with activated T-cells can eliminate chemoresistant triple-negative breast cancer (TNBC) cells in vitro.

Visualizing Energy Charge in Breast Carcinoma Tissues by MALDI Mass-spectrometry Imaging Profiles of Low-molecular-weight Metabolites.

Background/aim: Metabolomics is widely used for biomarker discovery, but conventional mass-spectrometry extraction procedures lose the spatial localization of metabolites. In this study, we directly analyzed breast carcinoma tissues embedded in frozen tissue microarrays (fTMAs) using MALDI mass-spectrometry imaging (MALDI-MSI).

Materials And Methods: A total of 119 breast tissues (84 carcinoma and 35 normal) were used.

BRCAness Combined With a Family History of Cancer Is Associated With a Poor Prognosis for Breast Cancer Patients With a High Risk of BRCA Mutations.

Background: The inexpensive prediction of the characteristics of BRCA-mutated breast cancer as "BRCAness" using the somatic cells of patients with breast cancer could be useful for developing a therapeutic strategy. Our objective was to correlate BRCAness with the clinicopathologic features, including a family history (FH) of cancer, in breast cancer patients with a high risk of BRCA mutations.

Patients And Methods: The present study included 124 patients, including 55 with early-onset and 77 with triple-negative breast cancer, who had undergone resection at Kyushu University Hospital from 2005 to 2014.

Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR/HER2 Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant.

Therapeutic strategies against hormonal receptor-positive (HR)/HER2 breast cancers with poor response to trastuzumab need to be optimized. Two HR/HER2 patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2 breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by drug efficacy examination and cell proliferation analysis.

[Efficacy of GC Therapy for the Patient of iTNBC with Resistance to TAC Therapy].

We report a case of TNBC treated effectively with a platinum-based regimen after developing resistance to anthracycline and taxane-based neoadjuvant chemotherapy(NAC). A 59-year-old woman with a right breast mass and high fever visited our clinic and was diagnosed as having inflammatory triple negative breast cancer(iTNBC). She was treated with NAC of docetaxel, doxorubicin, and cyclophosphamide(TAC)using pegfilgrastim.

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer.

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.

BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.

Methods: The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue.