Development and Validity Testing of an Assessment Tool for Domestic Elder Abuse.

BACKGROUND: The older adult population is increasing in number, and elder abuse is expected to become a more pressing problem. Developing tools to assess the presence and severity of elder abuse is important to both effectively prevent this abuse and provide increased support for families. PURPOSE: This study was intended to test the validity of an Assessment Tool for Domestic Elder Abuse (ATDEA). The items that constitute this tool were derived from a literature review. METHODS: Two rounds of self-administered questionnaire surveys were conducted with nurses working at home-visit nursing stations. Round 1 was used to evaluate the face validity, and Round 2 was used to test the content using the content validity index (CVI). RESULTS: Two hundred forty nurses participated in the two studies. In Round 1, 56 nurses evaluated 38 items derived from a literature review, resulting in the development of a 36-item ATDEA. In Round 2, 184 nurses evaluated the content validity of the 36-item ATDEA. The Item-CVI (I-CVI) scores ranged from .61 to 1. Twenty-eight of the items met or exceeded the I-CVI threshold of .78, whereas the eight items assessing self-neglect did not. The overall Scale-CVI score for the assessment tool was .90, which met the threshold of .90. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of validity testing established the preliminary validity of this assessment tool. In addition, as self-neglect is known to damage the well-being of older adults, six of the eight items assessing self-neglect were retained in the ATDEA despite their failure to meet the threshold I-CVI of .78. The remaining two self-neglect items were not included in the ATDEA because of excessively low I-CVI scores (< .70). Thus, the final version of the ATDEA includes 34 items. The authors recommend that nursing professionals use the ATDEA as a checklist to assess the presence of elder abuse and to discern the subtypes and severity of this abuse. When evaluating elder abuse, the higher the degree of severity, the greater the urgency to provide support.

Frequent downregulation of LRRC26 by epigenetic alterations is involved in the malignant progression of triple-negative breast cancer.

Triple-negative breast cancer (TNBC), defined as breast cancer lacking estrogen- and progesterone­receptor expression and human epidermal growth factor receptor 2 (HER2) amplification, is a heterogeneous disease. RNA-sequencing analysis of 15 TNBC specimens and The Cancer Genome Atlas-TNBC dataset analysis identified the frequent downregulation of leucine-rich repeat-containing 26 (LRRC26), which negatively regulates nuclear factor-κB (NF-κB) signaling, in TNBC tissues. Quantitative polymerase chain reaction and bisulfite pyrosequencing analyses revealed that LRRC26 was frequently silenced in TNBC tissues and cell lines as a result of promoter methylation. LRRC26 expression was restored by 5-aza-2'-deoxycytidine (5'-aza-dC) treatment in HCC1937 TNBC cells, which lack LRRC26 expression. Notably, small interfering RNA-mediated knockdown of LRRC26 expression significantly enhanced the anchorage-independent growth, invasion and migration of HCC70 cells, whereas ectopic overexpression of LRRC26 in BT20 cells suppressed their invasion and migration. Conversely, neither knockdown nor overexpression of LRRC26 had an effect on cell viability in the absence of tumor necrosis factor-α (TNF-α) stimulation. Meanwhile, overexpression of LRRC26 caused the reduction of TNF-α-mediated NF-κB luciferase reporter activity, whereas depleting LRRC26 expression resulted in the upregulation of TNF-α-mediated NF-κB downstream genes [interleukin-6 (IL-6), IL-8 and C-X-C motif chemokine ligand-1]. Taken together, these findings demonstrate that LRRC26 is frequently downregulated in TNBC due to DNA methylation and that it suppresses the TNF-α-independent anchorage-independent growth, invasion and migration of TNBC cells. Loss of LRRC26 function may be a critical event in the aggressiveness of TNBC cells through a TNF-α/NF-κB-independent mechanism.

Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics.

Estradiol (E2) and the oestrogen receptor-alpha (ERα) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERα signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ERα activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from α-helical BIG3 sequence, resulted in a significant anti-tumour effect. However, the duration of this effect was very short for viable clinical application. We developed the chemically modified ERAP using stapling methods (stapledERAP) to improve the duration of its antitumour effects. The stapledERAP specifically inhibited the BIG3-PHB2 interaction and exhibited long-lasting suppressive activity. Its intracellular localization without the membrane-permeable polyarginine sequence was possible via the formation of a stable α-helix structure by stapling. Tumour bearing-mice treated daily or weekly with stapledERAP effectively prevented the BIG3-PHB2 interaction, leading to complete regression of E2-dependent tumours in vivo. Most importantly, combination of stapledERAP with tamoxifen, fulvestrant, and everolimus caused synergistic inhibitory effects on growth of breast cancer cells. Our findings suggested that the stapled ERAP may be a promising anti-tumour drug to suppress luminal-type breast cancer growth.

A-kinase anchoring protein BIG3 coordinates oestrogen signalling in breast cancer cells.

Approximately 70% of breast cancer cells express oestrogen receptor alpha (ERα). Previous studies have shown that the Brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex has a crucial role in these cells. However, it remains unclear how BIG3 regulates the suppressive activity of PHB2. Here we demonstrate that BIG3 functions as an A-kinase anchoring protein that binds protein kinase A (PKA) and the α isoform of the catalytic subunit of protein phosphatase 1 (PP1Cα), thereby dephosphorylating and inactivating PHB2. E2-induced PKA-mediated phosphorylation of BIG3-S305 and -S1208 serves to enhance PP1Cα activity, resulting in E2/ERα signalling activation via PHB2 inactivation due to PHB2-S39 dephosphorylation. Furthermore, an analysis of independent cohorts of ERα-positive breast cancers patients reveal that both BIG3 overexpression and PHB2-S39 dephosphorylation are strongly associated with poor prognosis. This is the first demonstration of the mechanism of E2/ERα signalling activation via the BIG3-PKA-PP1Cα tri-complex in breast cancer cells.

Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis.

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful.

BACKGROUND: Serum E2 must be monitored for aromatase inhibitor (AI) therapy, but conventional assays lack sensitivity. SUBJECTS/METHODS: Forty amenorrheic breast cancer patients scheduled for AI treatment but requiring hormonological confirmation of their menopausal status were studied. Serum E2 data generated by high-sensitivity RIA and by LC-MS/MS were analyzed for correlation. RESULTS: RIA gave a higher E2 value than LC-MS/MS in 62% of cases, but there was a significant positive correlation. Patients whose E2 levels by RIA were ≥ 2.5 pg/mL higher than those by LC-MS/MS (RIA-H group) and all other patients (RIA-N group) were compared. Both groups showed strong correlations between the two assay methods. With both methods patients with a high BMI had significantly elevated E2. Multiple regression analysis used age, age at menarche, number of births and BMI as explanatory variables. Significant variables were the BMI with LC-MS/MS, and both BMI and age with RIA. The RIA-H and RIA-N groups showed no difference in regard to the BMI, whereas the age was significantly lower in the RIA-H group. SUMMARY: Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.

Immunocytochemical results for HER2 and Ki67 in breast cancer touch-smear cell specimens are reliable.

BACKGROUND: Re-evaluation of the subtype of recurrent breast cancer is necessary for deciding the treatment approach, but it is often not performed due to the difficulty of obtaining tissue specimens from a recurrent lesion, etc. However, when a recurrent lesion is close to the body surface, fine-needle aspiration cells (FNA cells) can be easily obtained, and immunocytochemical (ICC) analysis of hormone receptors expression in FNA cells is said to be highly reliable. However, there is no consensus regarding ICC analysis of human epidermal growth factor receptor type 2 (HER2) expression and the Ki67 index using FNA cells. METHODS: Touch-smear cells (TSC) were prepared from resected specimens from 36 patients with primary invasive ductal carcinoma of the breast. The TSC were fixed in 95 % ethanol and subjected to ICC analysis for HER2 using HercepTest™ (Dako) and Ki67 using MIB-1™ (Dako). HER2 expression and the Ki67 index for the TSC were compared with the results of immunohistochemical analysis of histological section (HS). Statistical analyses used the kappa test and Pearson's correlation coefficients. RESULTS: HER2 and Ki67 were analyzed in TSC from 36 and 28 patients, respectively. The HER2 expression scores in the TSC and HS groups showed good agreement (kappa value =0.640) and significant correlation (correlation coefficient =0.860, p < 0.001). The Ki67 indexes in the TSC and HS groups also showed significant correlation (correlation coefficient =0.861, p < 0.001). CONCLUSIONS: The reliability of ICC analysis of HER2 expression and the Ki67 index using TSC were recognized.

Therapeutic advances in BIG3-PHB2 inhibition targeting the crosstalk between estrogen and growth factors in breast cancer.

Our previous studies demonstrated that specific inhibition of the BIG3-PHB2 complex, which is a critical modulator in estrogen (E2) signaling, using ERAP, a dominant negative peptide inhibitor, leads to suppression of E2-dependent estrogen receptor (ER) alpha activation through the reactivation of the tumor suppressive activity of PHB2. Here, we report that ERAP has significant suppressive effects against synergistic activation caused by the crosstalk between E2 and growth factors associated with intrinsic or acquired resistance to anti-estrogen tamoxifen in breast cancer cells. Intrinsic PHB2 released from BIG3 by ERAP effectively disrupted each interaction of membrane-associated ERα and insulin-like growth factor 1 receptor beta (IGF-1Rß), EGFR, PI3K or human epidermal growth factor 2 (HER2) in the presence of E2 and the growth factors IGF or EGF, followed by inhibited the activation of IGF-1Rß, EGFR or HER2, and reduced Akt, MAPK and ERα phosphorylation levels, resulting in significant suppression of proliferation of ERα-positive breast cancer cells in vitro and in vivo. More importantly, combined treatment with ERAP and tamoxifen led to a synergistic suppression of signaling that was activated by crosstalk between E2 and growth factors or HER2 amplification. Taken together, our findings suggest that the specific inhibition of BIG3-PHB2 is a novel potential therapeutic approach for the treatment of tamoxifen-resistant breast cancers activated by the crosstalk between E2 and growth factor signaling, especially in premenopausal women.

Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions.

Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, the precise mechanism of the antitumour effects of XN on oestrogen (E2)-dependent cell growth, and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus on whether XN directly binds to the tumour suppressor protein prohibitin 2 (PHB2), forming a novel natural antitumour compound targeting the BIG3-PHB2 complex and acting as a pivotal modulator of E2/ERα signalling in breast cancer cells. XN treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERα. This event led to the complete suppression of the E2-signalling pathways and ERα-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that XN may be a promising natural compound to suppress the growth of luminal-type breast cancer.

A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55).

BACKGROUND: Autosomal recessive hereditary spastic paraplegias (AR-HSP) constitute a heterogeneous group of neurodegenerative diseases involving pyramidal tracts dysfunction. The genes responsible for many types of AR-HSPs remain unknown. We attempted to identify the gene responsible for AR-HSP with optic atrophy and neuropathy. METHODS: The present study involved two patients in a consanguineous Japanese family. Neurologic examination and DNA analysis were performed for both patients, and a skin biopsy for one. We performed genome-wide linkage analysis involving single nucleotide polymorphism arrays, copy-number variation analysis, and exome sequencing. To clarify the mitochondrial functional alteration resulting from the identified mutation, we performed immunoblot analysis, mitochondrial protein synthesis assaying, blue native polyacrylamide gel electrophoresis (BN-PAGE) analysis, and respiratory enzyme activity assaying of cultured fibroblasts of the patient and a control. RESULTS: We identified a homozygous nonsense mutation (c.394C>T, p.R132X) in C12orf65 in the two patients in this family. This C12orf65 mutation was not found in 74 Japanese AR-HSP index patients without any mutations in previously known HSP genes. This mutation resulted in marked reduction of mitochondrial protein synthesis, followed by functional and structural defects in respiratory complexes I and IV. CONCLUSIONS: This novel nonsense mutation in C12orf65 could cause AR-HSP with optic atrophy and neuropathy, resulting in a premature stop codon. The truncated C12orf65 protein must lead to a defect in mitochondrial protein synthesis and a reduction in the respiratory complex enzyme activity. Thus, dysfunction of mitochondrial translation could be one of the pathogenic mechanisms underlying HSPs.

Among triple-negative breast cancers, HER2(0) breast cancer shows a strong tendency to be basal-like compared with HER2(1+) breast cancer: preliminary results.

BACKGROUND: Diagnosis of triple-negative breast cancer (ER-negative, PgR-negative, HER2-negative; TNBC) is performed by means of immunohistological staining. HER2-negative includes HER2(0) and HER2(1+), based on differences in the staining intensity, but there have been no reports on comparison of these two types in TNBC. Accordingly, this study was designed to investigate the possible differences in the biological characteristics of HER2(0) breast cancer and HER2(1+) breast cancer in TNBC. METHODS: Tissue specimens from 89 TNBC patients were immunohistochemically stained for CK5/6, EGFR, p53, Ki67, E-cadherin, TOP2A and Bcl-2. The expressions of these markers and the clinicopathological findings were compared between the HER2(0) patient group and the HER2(1+) patient group. When either CK5/6 or EGFR was positive, the specimen was judged to be the basal-like phenotype of breast cancer. RESULTS: The percentages of CK5/6- and/or EGFR-positive specimens in the HER2(0) and HER2(1+) groups were 44.9 and 16.8%, respectively, showing that there was a significantly greater number of basal-like phenotype patients in the HER2(0) group (p < 0.01). The percentage of E-cadherin-positive specimens in the HER2(0) group was 66.6%, which was significantly greater than the 40.0% recorded in the HER2(1+) group (p < 0.05). The respective percentages of TOP2A-positive specimens in the HER2(0) and HER2(1+) groups were 55.0 and 30.0%, and the difference was statistically significant (p < 0.05). CONCLUSION: In TNBC, HER2(0) breast cancer showed a strong tendency to include more of the basal-like phenotype compared with HER2(1+) breast cancer. The staining results indicated the possibility that HER2(0) breast cancer and HER2(1+) breast cancer have different characteristics.

A novel adult case of juvenile-onset Alexander disease: complete remission of neurological symptoms for over 12 years, despite insidiously progressive cervicomedullary atrophy.

We present here a 25-year-old woman with genetically confirmed (p.R276L mutation in the GFAP gene) juvenile-onset AxD. Episodic vomiting appeared at age nine, causing anorexia and insufficient growth. Brain MRI at age 11 showed a small nodular lesion with contrast enhancement in the left dorsal portion of the cervicomedullary junction. Her episodic vomiting improved spontaneously at age 13, and she became neurologically asymptomatic. The enhancement of the lesion disappeared simultaneously, although the plaque remained. Longitudinal MRI observations, however, revealed insidiously progressive cervicomedullary atrophy without a signal change. This case broadens our knowledge of AxD: (1) molecular analysis of the GFAP gene is warranted in patients with MRI evidence of tumor-like lesions in the brainstem, particularly if they present with isolated episodic vomiting and/or anorexia; (2) the disease can be self-remitting for at least 12 years; (3) cervicomedullary atrophy, characteristic of the adult form, can be insidiously progressive without a signal change before the clinical symptoms appear.

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia.

BACKGROUND: The clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear. METHODS: AIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fisher's exact test and logistic regression analysis). RESULTS: The mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of < 55, 55-65 and > 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for < 12, 12-15 and > 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) < 5 years, 5-10 years and > 10 years, being significantly lower at > 10 years (p < 0.001). In logistic regression analysis, the AIA incidence was significantly lower in the time since LMP > 10-year group versus the < 5-year group (odds ratio 0.44, p = 0.002), but the age at menarche showed no association. AIA manifested significantly earlier (≤ 6 months) as the time since LMP became shorter (< 5 years). CONCLUSION: AIA tends to manifest early after starting AI, but some cases show delayed onset. The incidence was significantly lower in patients with a duration of > 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration.

Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer.

BACKGROUND: Elucidation of the biological features of triple negative breast cancer (TNBC) is important for deciding treatment strategies. The expression of a number of biomarkers in TNBC was analyzed to elucidate those features. PATIENTS AND METHODS: The subjects were 134 TNBC patients. Immunohistochemical staining was employed to analyze for eight biomarkers: cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), p53, Ki-67 antigen (Ki-67), E-cadherin, N-cadherin, topoisomerase 2 alpha (TOP2A) and B-cell lymphoma 2 (BCL-2), which were then correlated with the nuclear grade (NG), tumor diameter, and the presence/absence of lymph node metastasis, distant recurrence and lymphatic infiltration. RESULTS: Significantly more high than low NG TNBC exhibited positive p53, Ki-67, E-cadherin and TOP2A. High N-cadherin and TOP2A expression was shown significantly in TNBC with lymphatic infiltration, and N-cadherin was also significantly positively expressed in node metastasis-positive cases. EGFR and CK5/6 were positively expressed in high NG TNBC, but not significantly. CONCLUSION: Analysis for expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A is meaningful for deciding treatment strategies for TNBC.

Genome-wide association study of epirubicin-induced leukopenia in Japanese patients.

OBJECTIVES: Despite long-term clinical experience with epirubicin, unpredictable severe adverse reactions remain an important determinant to limit the drug use. To identify a genetic factor(s) affecting the risk of epirubicin-induced leukopenia/neutropenia, we performed a genome-wide association study. METHODS: We studied 270 patients consisting of 67 patients with grade 3 or 4 leukopenia/neutropenia, and 203 patients showing no toxicity (patients with grade 1 or 2 were excluded from the study) for genome-wide association study. We further examined the single nucleotide polymorphisms (SNPs) showing P values of less than 0.0001 using an additional set of 48 patients with grade 3/4 leukopenia/neutropenia. RESULTS: The combined analysis indicated that rs2916733 in microcephalin 1 [combined PFisher min=2.27×10, odds ratio (OR)=2.74 with 95% confidence interval (CI)=1.96-3.83; the nonrisk genotype as reference] was significantly associated with epirubicin-induced leukopenia/neutropenia. A subgroup analysis of patients with only breast cancer showed a similar trend of association for the marker SNP rs2916733 (combined PFisher min=6.76×10, OR=2.80 with 95% CI=1.86-4.21). We subsequently performed haplotype analysis and found that a haplotype constructed from rs2916733 and rs1031309, which was in linkage disequilibrium with rs2916733 (r=0.64), showed stronger association (P=2.20×10, OR=2.88 with 95% CI=2.05-4.03) than a single landmark SNP (rs2916733; P=2.27×10, OR=2.74 with 95% CI=1.96-3.83), suggesting that causative variant(s) that could influence the susceptibility of epirubicin-induced adverse drug reactions (ADRs) might exist in this haplotype. CONCLUSION: Our findings show that genetic variants in the microcephalin 1 locus are suggestively associated with the risk of epirubicin-induced ADRs and might be applicable in development of diagnostic system for predicting the risk of the ADRs, leading to better prognosis and quality of life for patients with cancer. However, these results should be considered preliminary until replicated in adequately larger powered and controlled samples.

Joint symptoms, aromatase inhibitor-related adverse reactions, are indirectly associated with decreased serum estradiol.

Background. Joint symptoms (JSs) are problematic adverse drug reactions (ADRs) of aromatase inhibitors (AIs). Involvement of decreased serum estradiol (SE) has been suggested. Patients and Methods. 104 postmenopausal breast cancer patients administered an AI were prospectively investigated regarding various clinical parameters, JS and hot flashes as ADRs, and the SE level. Results. JS manifested in 31.7% of patients and hot flashes in 18.3%. Chi-square testing showed a significantly higher incidence of JS in several patient strata: <55 years old, decreased SE, and elevated total cholesterol (TC). In univariate analysis, JS correlated significantly with a pre-AI % YAM of ≥80%, decreased SE, and elevated TC. Eight (7.7%) patients maintained SE at ≥5 pg/mL for >6 consecutive months, with no JS. In chi-square testing, hot flashes showed a significantly higher incidence in patients <55 years old. Conclusion. AI-ADRs occurred more readily in younger patients. Decreased SE may be indirectly involved in JS.

Serum estradiol should be monitored not only during the peri-menopausal period but also the post-menopausal period at the time of aromatase inhibitor administration.

BACKGROUND: Aromatase inhibitor (AI) therapy is being extensively used as postoperative adjuvant therapy in patients with hormone receptor-positive postmenopausal breast cancer. On the other hand, it has been reported that ovarian function was restored when AI was administered to patients who had undergone chemical menopause with chemotherapy or tamoxifen. However, there have been no reports of comprehensive monitoring of estradiol (E2) in breast cancer patients with ordinary menopause who were being administered AI. PATIENTS AND METHODS: Beginning in March 2008, regular monitoring of the serum levels of E2, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed for 66 postmenopausal breast cancer patients who had been started on AI therapy. For this study, we chose anastrozole as the AI. The assays of those hormones were outsourced to a commercial clinical laboratory. RESULTS: In 4 of the 66 patients the serum E2 level was decreased at 3 months but had then increased at 6 months, while in 2 other patients E2 was decreased at both 3 and 6 months but had increased at 9 months. CONCLUSION: The results indicate that, in some breast cancer patients with ordinary menopause, E2 rebounds following AI therapy. In the future, E2 monitoring should be performed for a larger number of patients being administered AI therapy. TRIAL REGISTRATION: Our trial registration number is 19-11-1211.

A case of matrix-producing carcinoma of the breast.

BACKGROUND: Matrix-producing carcinoma (MPC) of the breast is one variant type of metaplastic carcinoma. The cellular origin of MPC remains unclear. It has been suggested the tumor cells in MPC have the combined characteristics of both epithelial cells and mesenchymal cells. Several reports suggested that the tumor cells in MPC might originate from the myoepithelial cells, but others suggested the origin was basal-like cells. CASE PRESENTATION: The patient was a 42-year-old Japanese female. A tumor of about 2 cm in diameter was noted in the right breast. CT revealed the circumference of the tumor to have a ring-like structure, and fine needle aspiration cytology indicated suspicion for malignancy. Breast-conserving surgery was performed. Histopathological studies showed carcinoma cells, having cuboidal to oval-shaped nucleus, were proliferating in cord-like and sheet-like structures in the periphery. In the central areas of the tumor, myxoedematous area was observed with cartilaginous matrix and necrosis. The diagnosis was a matrix-producing carcinoma. Immunohistochemical findings showed the tumor cells had the characteristics of both epithelial cells and mesenchymal cells, while being negative for estrogen receptor, progesterone receptor, Her2, myoepithelial cell markers and basal cell markers. CONCLUSION: The findings for our present patient and many of the other MPC patients reported in the published literature indicate that this breast cancer has the properties of both epithelial cells and mesenchymal cells. In addition, there is a possibility that matrix-producing tumor cells of our present patient may have a feature of undifferentiated cells.

[Complete response in a case of advanced esophageal cancer treated with docetaxel/5-FU/CDDPand S-1/docetaxel as neoadjuvant chemotherapy].

A 64-year-old woman with advanced esophageal cancer underwent chemotherapy with docetaxel/5-FU/CDDP (DFP). Adverse reactions were severe nausea and general fatigue, so the patient decided to discontinue DFP therapy. The treatment was changed to S-1/docetaxel. Adverse reactions were not so severe, so she could receive 1 course of the medication completely. After the treatment, the primary lesion showed a partial response, so we performed surgery. In the resected specimen, no malignant cell could be seen microscopically. Though the advanced esophageal cancer was regarded as a systemic disease, the appropriate combination of chemotherapy and surgery proved effective.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results.

Capecitabine monotherapy was administered for 25 patients with advanced or recurrent breast cancer, and the clinical therapeutic efficacy and its relationship to expression of 5-fluorouracil-related enzymes (i. e., thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)) were investigated. The expressions of TP, TS and DPD were determined by immunohistochemical staining techniques and rated using a scoring system of 1~4. The expression score for TP/DPD showed a statistically significant correlation with the clinical response, whereas the expression score for TP/TS also showed a correlation but it was not statistically significant. The number of patients was small, but the results revealed the potential of application of the TP/DPD expression score as a factor for predicting the efficacy of the drug in individual patients.