Clinicopathogenomic analysis of PI3K/AKT/PTEN-altered luminal metastatic breast cancer in Japan.

This rapid communication highlights the correlation between protein kinase B alpha (AKT1)-phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)- phosphatase and tensin homolog (PTEN) alterations and clinicopathological factors in Japanese patients with metastatic recurrent breast cancer (mBC). This study analyzed 1967 patients with luminal-type breast cancer who underwent cancer gene panel testing. The results demonstrated that AKT pathway alterations, including PI3K/AKT/PTEN, occurred in 1038 (52.

Surgical and irradiated case of early breast cancer in a patient with Ehlers-Danlos syndrome.

Background: Ehlers-Danlos syndrome (EDS) is a rare inherited connective tissue disease characterized by hyperextensibility of the skin and joints and tissue fragility of the skin and blood vessels, Vascular EDS is the most severe form of EDS, with abnormal arterial fragility. There have been no reports of breast cancer occurring in patients with vascular EDS. Here, we report here a very rare case of breast cancer in a patient with vascular EDS.

Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.

Background: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.

Immunolocalization of Cytoplasmic ER in ER-negative Breast Carcinoma as a Potent Favorable Prognostic Predictor.

It is known that estrogen receptor (ER) has extranuclear signaling functions in addition to classical genomic pathway, and estrogenic actions have been reported in ER-negative breast carcinoma cells. However, significance of cytoplasmic-ER immunoreactivity has not been reported in ER-negative breast carcinoma tissues. We immunolocalized cytoplasmic ER in 155 ER-negative breast carcinoma tissues and evaluated its clinicopathological significance including the prognosis.

Risk Analysis of Breast Cancer by Using Bilateral Mammographic Density Differences: A Case-Control Study.

The identification of risk factors helps radiologists assess the risk of breast cancer. Quantitative factors such as age and mammographic density are established risk factors for breast cancer. Asymmetric breast findings are frequently encountered during diagnostic mammography.

Kallikrein-Related Peptidase 12 (KLK12) in Breast Cancer as a Favorable Prognostic Marker.

Kallikrein-related peptides (KLKs) form an evolutionally conserved subgroup of secreted serine proteases that consists of 15 members (KLK1-15). Previous studies have shown that KLKs regulate diverse biological processes, but the clinical significance of KLKs remains largely unclear in human breast cancers. We examined the expression profile of 15 KLK genes in breast carcinomas using microarray data.

Forkhead Box I1 in Breast Carcinoma as a Potent Prognostic Factor.

Forkhead box (FOX) proteins are family of transcriptional factors and regulate cell growth and differentiation as well as embryogenesis and longevity. Previous studies have demonstrated that several FOX members regulate growth or metastasis of breast carcinoma, but clinical significance of total FOX members remains unclear. We first examined associations between expression of 40 FOX genes and TNM status of 19 breast carcinoma using microarray data.

Targeting Amino Acid Metabolic Reprogramming via L-Type Amino Acid Transporter 1 (LAT1) for Endocrine-Resistant Breast Cancer.

The PI3K/Akt/mTOR pathway has been well known to interact with the estrogen receptor (ER)-pathway and to be also frequently upregulated in aromatase inhibitor (AI)-resistant breast cancer patients. Intracellular levels of free amino acids, especially leucine, regulate the mammalian target of rapamycin complex 1 (mTORC1) activation. L-type amino acid transporters such as LAT1 and LAT3 are associated with the uptake of essential amino acids.

Establishment of an analytical method for simultaneous quantitation of CDK4/6 inhibitors, aromatase inhibitors, and an estrogen receptor antagonist in human plasma using LC-ESI-MS/MS.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors (palbociclib, abemaciclib, and ribociclib) are used to treat human epithelial growth factor receptor (HER)-2 negative and hormone receptor (HR) positive advanced breast cancer in combination with aromatase inhibitors (letrozole, anastrozole) or an estrogen receptor antagonist (fulvestrant). Administration of these drugs frequently causes severe side effects, such as neutropenia and diarrhea. Therefore, therapeutic drug monitoring (TDM) of CDK4/6 inhibitors, aromatase inhibitors, and the estrogen receptor antagonist is considered important for ensuring the efficacy and safety of these drugs.

Minimal impact of postmastectomy radiation therapy on locoregional recurrence for breast cancer patients with 1 to 3 positive lymph nodes in the modern treatment era.

Introduction: Given modern treatment strategies, controversy remains regarding whether postmastectomy radiation therapy (PMRT) is necessary for breast cancer patients with 1-3 positive axillary lymph nodes (ALN). Our aim was to assess the significance of PMRT in the modern treatment era for these patients.

Material And Methods: We have conducted the retrospective multicenter study and identified 658 patients with 1-3 positive ALN who were treated with mastectomy and ALN dissection between 1999 and 2012.

Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis.

It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of comedo DCIS based on microarray data and identified CYC1 as a gene associated with comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production.

Changes in Streptococcus pneumoniae serotypes in the nasopharynx of Japanese children after inoculation with a heptavalent pneumococcal conjugate vaccine.

In this study, we prospectively investigated changes in Streptococcus pneumoniae serotypes among Japanese children after heptavalent pneumococcal conjugate vaccine (PCV7) inoculation. We acquired nasopharyngeal swabs from the children at each routine PCV7 inoculation and again at least 2 months after the last PCV7 inoculation. We defined 2 periods with regard to each culture: the inoculation period as "the period of pre- or incomplete vaccination" and post-inoculation as "the period of post- or completed vaccination.

Identification of androgen-responsive microRNAs and androgen-related genes in breast cancer.

Background: Androgen receptors (ARs) are expressed in many breast cancer cells, but the mechanism of action of androgens is not as well-characterized as in other cell types. The study of microRNAs has recently provided with important insights into the biology of hormone-dependent cancer.

Materials And Methods: We attempted to identify microRNAs induced by dihydrotestosterone in an AR-positive cell line.

Prevalence and risk factors of nasopharyngeal carriage of Streptococcus pneumoniae in healthy children in Japan.

The findings of this study revealed a 22% prevalence of Streptococcus pneumoniae among healthy children in Japan; the prevalence tended to increase with age. We identified attendance at day-care facilities and the presence of older siblings as the major risk factors associated with pneumococcal carriage. A significant decrease in pneumococcal colonization was observed among children during the summer; however, a seasonal variation was independent of various factors.

BUB1 immunolocalization in breast carcinoma: its nuclear localization as a potent prognostic factor of the patients.

Mitotic checkpoint is a fundamental mechanism involved in fidelity mitotic chromosome segregation, and its alteration results in progression of human malignancies. In this study, we examined expression profiles of seven mitotic checkpoint genes in 20 breast carcinomas using microarray analysis. Results demonstrated that BUB1 expression level was closely correlated with the proliferation activity evaluated by Ki-67 labeling index (LI) of individual cases.

Intratumoral estrogen concentration and expression of estrogen-induced genes in male breast carcinoma: comparison with female breast carcinoma.

It is speculated that estrogens play important roles in the male breast carcinoma (MBC) as well as the female breast carcinoma (FBC). However, estrogen concentrations or molecular features of estrogen actions have not been reported in MBC, and biological significance of estrogens remains largely unclear in MBC. Therefore, we examined intratumoral estrogen concentrations, estrogen receptor (ER) α/ERβ status, and expression profiles of estrogen-induced genes in MBC tissues, and compared these with FBC.

Oestrogen-induced genes in ductal carcinoma in situ: their comparison with invasive ductal carcinoma.

It is well known that oestrogens play important roles in both the pathogenesis and development of invasive ductal carcinoma (IDC) of human breast. However, molecular features of oestrogen actions have remained largely unclear in pure ductal carcinoma in situ (pDCIS), regarded as a precursor lesion of many IDCs. This is partly due to the fact that gene expression profiles of oestrogen-responsive genes have not been examined in pDCIS.

Nucleobindin 2 in human breast carcinoma as a potent prognostic factor.

It is well-known that estrogens immensely contribute to the progression of human breast carcinoma, but their detailed molecular mechanisms remain largely unclear. In this study, we identified nucleobindin 2 (NUCB2) as a gene associated with recurrence based on microarray data of estrogen receptor (ER)-positive breast carcinoma cases (n = 10), and subsequent in vitro study showed that NUCB2 expression was upregulated by estradiol in ER-positive MCF-7 cells. However, NUCB2 has not yet been examined in breast carcinoma, and its significance remains unknown.