Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer.

In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as HER2 heterogeneity. We investigated the clinicopathological features of patients with HER2 heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for HER2 heterogeneity, we used dual in situ hybridization slides. We evaluated the association between HER2 heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with HER2 heterogeneity. The pCR rates were 13.3% among patients with HER2 heterogeneity and 20.8% among those with HER2 nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with HER2 heterogeneity than in those without (P = 0.025). HER2 heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.

GNAS mutations in adrenal aldosterone-producing adenomas.

Mutations in GNAS, which encodes Gsα, have been documented in detail, particularly in human pituitary GH-secreting adenomas. Mutations have also recently been reported in adrenal cortisol-producing adenomas (CPAs), in addition to those in the PRKACA gene. However, mutations have not yet been examined in aldosterone-producing adenomas (APAs). Therefore, we herein investigated mutations in the GNAS gene in APAs. Two of the 15 (13%) CPAs with overt Cushing's syndrome and one of the 9 (11%) CPAs with subclinical Cushing's syndrome examined had the somatic mutations, p.R201S and p.R201C in the GNAS gene. We identified mutations in the GNAS gene (p.R201C) in 2 out of the 33 (6%) APAs tested, both of which showed autonomous cortisol secretion, while 24 APAs had mutations in the KCNJ5 gene (18 with p.G151R and 6 with p.L168R). These GNAS and KCNJ5 mutations were mutually exclusive in these adenomas. We herein demonstrated for the first time the presence of GNAS mutations in APAs, as well as in some cortisol-secreting adenomas. Our results suggest that these mutations, in addition to mutations in the KCNJ5 gene and other genes such as ATP1A1, ATP2B3 and CACNA1D, may be responsible for the tumorigenesis of APAs and CPAs with subclinical Cushing's syndrome.

Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with several adrenal adenomas secreting cortisol [Rapid Communication].

Somatic mutations of the catalytic subunit of the cyclic AMP-dependent protein kinase (PRKACA) gene have recently been identified in about 35% of cortisol-producing adenomas (CPAs), with the affected patients showing overt Cushing's syndrome. Since we recently reported higher prevalence of mutations of the KCNJ5 gene and associations with autonomous cortisol secretion in Japanese aldosterone-producing adenomas than in Western countries, there might be different features of CPAs between Japan and the West. We therefore investigated mutations of the PRKACA gene in Japanese patients with several adrenal tumors secreting cortisol, including overt Cushing's syndrome, subclinical Cushing's syndrome, and aldosterone-producing adenomas (APAs) co-secreting cortisol operated on at Gunma University Hospital. Of the 13 patients with CPA who showed overt Cushing's syndrome, 3 (23%) had recurrent somatic mutations of the PRKACA gene, p.L206R (c.617 T>G), and there were no mutations in subclinical Cushing's syndrome. Among 33 APAs, 24 had somatic mutations of the KCNJ5 gene, either G151R or L168R, 11 (33%) had autonomous cortisol secretion, but there were no mutations of the PRKACA gene. We established a PCR-restriction fragment length polymorphism assay and revealed that the mutated allele was expressed at a similar level to the wild-type allele. These findings demonstrated that 1) the prevalence of Japanese patients with CPA who showed overt Cushing's syndrome and whose somatic mutations in the PRKACA gene was similar to that in Western countries, 2) the mutation might be specific for CPAs causing overt Cushing's syndrome, and 3) the mutant PRKACA allele was expressed appropriately in CPAs.

[Phase I study of sequential S-1 and cyclophosphamide therapy in patients with metastatic breast cancer].

S-1 is a novel oral anticancer agent consisting of tegafur, a prodrug of 5-fluorouracil, and 2 modulators. A phase I study of sequential S-1 and cyclophosphamide(CPA)therapy was conducted to determine the dose-limiting toxicities(DLTs)and recommended doses(RDs)in patients with metastatic or recurrent breast cancer(MBC). Patients with MBC received sequential S-1 and CPA. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 50, 65, and 80mg/m2/day and CPA at 100 mg/body/day on days 15-28. The schedule was repeated twice at a 4-week interval. The purposes of this study were to determine the RDs, safety, and efficacy of the regimen. A total of 12 patients were registered. No patients experienced DLTs, and the RDs of S-1 and CPA were 80mg/m2/day and 100 mg/body/day, respectively. The response rate was 50. 0%. In conclusion, sequential therapy with S-1 and CPA could be safely and effectively used for the treatment of MBC, and the RDs for this regimen were determined to be 80mg/m2/day for S-1 and 100 mg/m2/day for CPA.

Identification and characterization of two novel genomic RNA segments of fig mosaic virus, RNA5 and RNA6.

Fig mosaic virus (FMV), a negative-strand RNA virus, is recognized as a causal agent of fig mosaic disease. We performed RT-PCR for 14 FMV isolates collected from symptomatic fig plants in Japan and Serbia using primers corresponding to the conserved 13 nt stretches found at the termini of FMV genomic segments. The resulting simultaneous amplification of all FMV genomic segments yielded four previously identified segments of FMV and two novel segments. These novel FMV genomic RNA segments were found in each of the 14 FMV isolates analysed. In Northern blot studies, both the sense and antisense strands of these novel RNA molecules accumulated in FMV-infected fig leaves but not in uninfected fig leaves, confirming that they replicate as FMV genomic segments. Sequence analysis showed that the novel RNA segments are similar, in their structural organization and molecular evolutionary patterns, to those of known FMV genomic RNA segments. Our findings thus indicate that these newly discovered RNA segments are previously unidentified FMV genomic segments, which we have designated RNA5 and RNA6.

Comparative Evaluation of Fatty Acid Composition, Tocopherols, and Volatile Compounds of Walnut Oil between Juglans mandshurica Maxim. var. sachalinensis (Komatsu) Kitam and J. regia L.

We investigated the fatty acid composition and regiospecific distribution of triacylglycerol in Juglans mandshurica Maxim. var. sachalinensis (Komatsu) Kitam and Juglans regia L. oils. Significant differences are observed in the fatty acid compositions and regiospecific distribution of triacylglycerol in both oils. In addition, we measured volatile compounds and tocopherol content in two walnut oils. In results of volatile compound analysis, vanillin is specifically detected from J. mandshurica var. sachalinensis oil, and was not detected in J. regia L. oil. Notably, γ-tocopherol content in the J. mandshurica var. sachalinensis oil was significantly higher than J. regia L. oil.

Phase II Study of Nab-paclitaxel Plus Cyclophosphamide Plus Trastuzumab Neoadjuvant Chemotherapy in Early HER-2-positive Breast Cancer.

BACKGROUND/AIM: This phase II trial evaluated the efficacy and safety of neoadjuvant nab-paclitaxel plus cyclophosphamide (CPA) plus trastuzumab (AbraC-HER) in patients with early HER2-positive breast cancer. PATIENTS AND METHODS: This was a single-arm, open-label, single-center prospective phase II study. The primary endpoint was pathological complete response rate (pCR rate). The secondary endpoints were clinical antitumor efficacy and the frequency and severity of adverse events. RESULTS: Fifty-nine patients were enrolled in this study. pCR (ypT0/is ypN0) was achieved in 29 patients (49%). The overall response rate was 88.1% (52/59) in all patients. Dose reductions because of adverse events occurred in 3 patients (5.1%) and relative dose intensity was 98%. Compared to Abra-HER, AbraC-HER induced fewer adverse effects. CONCLUSION: Treatment with nab-paclitaxel plus CPA plus trastuzumab was tolerable and effective with a high pCR rate. This AbraC-HER neoadjuvant therapy may be a feasible new treatment option for patients with early HER2-positive breast cancer.

Postharvest Properties of Ultra-Late Maturing Peach Cultivars and Their Attributions to Melting Flesh (M) Locus: Re-evaluation of M Locus in Association With Flesh Texture.

The postharvest properties of two ultra-late maturing peach cultivars, "Tobihaku" (TH) and "Daijumitsuto" (DJ), were investigated. Fruit were harvested at commercial maturity and held at 25°C. TH exhibited the characteristics of normal melting flesh (MF) peach, including rapid fruit softening associated with appropriate level of endogenous ethylene production In contrast, DJ did not soften at all during 3 weeks experimental period even though considerable ethylene production was observed. Fruit of TH and DJ were treated with 5,000 ppm of propylene, an ethylene analog, continuously for 7 days. TH softened rapidly whereas DJ maintained high flesh firmness in spite of an increase in endogenous ethylene production, suggesting that DJ but not TH lacked the ability to be softened in response to endogenous and exogenous ethylene/propylene. DNA-seq analysis showed that tandem endo-polygalacturonase (endoPG) genes located at melting flesh (M) locus, Pp-endoPGM (PGM), and Pp-endoPGF (PGF), were deleted in DJ. The endoPG genes at M locus are known to control flesh texture of peach fruit, and it was suggested that the non-softening property of DJ is due to the lack of endoPG genes. On the other hand, TH possessed an unidentified M haplotype that is involved in determination of MF phenotype. Structural identification of the unknown M haplotype, designated as M 0, through comparison with previously reported M haplotypes revealed distinct differences between PGM on M 0 haplotype (PGM-M0 ) and PGM on other haplotypes (PGM-M1 ). Peach M haplotypes were classified into four main haplotypes: M 0 with PGM-M0 ; M 1 with both PGM-M1 and PGF; M 2 with PGM-M1 ; and M 3 lacking both PGM and PGF. Re-evaluation of M locus in association with MF/non-melting flesh (NMF) phenotypes in more than 400 accessions by using whole genome shotgun sequencing data on database and/or by PCR genotyping demonstrated that M 0 haplotype was the common haplotype in MF accessions, and M 0 and M 1 haplotypes were dominant over M 2 and M 3 haplotypes and co-dominantly determined the MF trait. It was also assumed on the basis of structural comparison of M haplotypes among Prunus species that the ancestral haplotype of M 0 diverged from those of the other haplotypes before the speciation of Prunus persica.

Neoadjuvant weekly paclitaxel with and without trastuzumab in locally advanced or metastatic breast cancer.

A phase II clinical trial was conducted to examine the clinical and pathologic efficacy and safety of neoadjuvant paclitaxel with or without trastuzumab in women with advanced or metastatic breast cancer. A total of 49 patients with advanced or metastatic breast cancer (clinical stage IIB -IV) were included. Patients with HER2-negative tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break for 4 cycles. Patients with HER2-positive tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break and a trastuzumab 4 mg/kg loading dose, intravenously, followed by 2 mg/kg weekly for 4 cycles. The age of the patients was 51.6 +/- 1.6 years (mean +/- SE) and the size of their tumors was 5.8 +/- 0.4 cm (mean +/- SE). Thirty-two patients had HER2-negative tumors and 17 had HER2-positive tumors. Of 49 patients, 13 (26.5%) had a clinical complete response and 24 (49.0%) had a clinical partial response. Five (10.2%) patients had a pathological complete response (pCR) and three (6.1%) patients had a near pCR in the breast. A total of eight (16.3%) patients had a pCR or near pCR in the breast. The pCR or near pCR rate was 3.1% in the HER2-negative group and 41.2% in the HER2-positive group. With a median follow-up of 28 months (range, 1-45), the 3-year overall survival was 88%. Clinical responders showed a significantly better overall survival than non-responders (p < 0.01). Pathological responders showed a better overall survival than non-responders. There was no significant difference in overall survival between patients with HER2-positive and -negative tumors. In conclusion, combined neoadjuvant weekly paclitaxel and trastuzumab achieved high clinical and pathological response rates for HER2 -overexpressing breast cancers, despite the omission of an anthracycline.

Characterization of peach tree crown by using high-resolution images from an unmanned aerial vehicle.

In orchards, measuring crown characteristics is essential for monitoring the dynamics of tree growth and optimizing farm management. However, it lacks a rapid and reliable method of extracting the features of trees with an irregular crown shape such as trained peach trees. Here, we propose an efficient method of segmenting the individual trees and measuring the crown width and crown projection area (CPA) of peach trees with time-series information, based on gathered images. The images of peach trees were collected by unmanned aerial vehicles in an orchard in Okayama, Japan, and then the digital surface model was generated by using a Structure from Motion (SfM) and Multi-View Stereo (MVS) based software. After individual trees were identified through the use of an adaptive threshold and marker-controlled watershed segmentation in the digital surface model, the crown widths and CPA were calculated, and the accuracy was evaluated against manual delineation and field measurement, respectively. Taking manual delineation of 12 trees as reference, the root-mean-square errors of the proposed method were 0.08 m (R 2 = 0.99) and 0.15 m (R 2 = 0.93) for the two orthogonal crown widths, and 3.87 m2 for CPA (R 2 = 0.89), while those taking field measurement of 44 trees as reference were 0.47 m (R 2 = 0.91), 0.51 m (R 2 = 0.74), and 4.96 m2 (R 2 = 0.88). The change of growth rate of CPA showed that the peach trees grew faster from May to July than from July to September, with a wide variation in relative growth rates among trees. Not only can this method save labour by replacing field measurement, but also it can allow farmers to monitor the growth of orchard trees dynamically.

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

Background: We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. Methods: We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Results: Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). Conclusions: CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Significance of local recurrence as a prognostic factor in the treatment of breast cancer.

The aim of this study was to evaluate both the risk factors of local recurrence and the prognostic significance of local recurrence in relation to surgical treatment and/or radiation therapy of breast cancer. A total of 1574 primary breast cancer patients, undergoing surgical treatment and/or radiation therapy between 1980 and 2001, were included in this study. Radical mastectomy was performed in 1144 patients, subcutaneous mastectomy in 141 and breast-conserving therapy in 289. The clinical stage was significantly earlier in the subcutaneous mastectomy and breast-conserving therapy groups than in the radical mastectomy group. A positive surgical margin was observed in 9 (6.4%) out of 141 patients in the subcutaneous mastectomy group and 51 (176%) out of 289 in the breast-conserving therapy group. Local recurrence occurred more frequently in the subcutaneous mastectomy and breast-conserving therapy groups than in the radical mastectomy group. Independent prognostic factors in local recurrence were lymph node metastasis in the radical mastectomy group, and surgical margin in the subcutaneous mastectomy group and the breast-conserving therapy group. Independent prognostic factors in overall survival were local recurrence, lymph node metastasis and estrogen receptor status in the radical mastectomy group, and lymph node metastasis and estrogen receptor status in the breast-conserving therapy group. In conclusion, the surgical margin status is an important factor in the risk of local recurrence in patients who have undergone a subcutaneous mastectomy or breast-conserving therapy. The significance of local recurrence for overall survival may be different among these three treatments.

Clinicopathological Features of Cases with Primary Breast Cancer not Identified by 18F-FDG-PET.

Several studies have reported that high F18-fluorodeoxyglucose (FDG) uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. While these studies evaluated the prognostic value for cases with high FDG uptake, they did not elucidate the meaning of FDG negativity in primary breast cancer. In this study, we evaluated the clinicopathological features of breast cancer cases without FDG uptake. We retrospectively investigated the cases of 219 consecutive patients with primary breast cancer who underwent FDG-positron emission tomography (PET) preoperatively. Among the 219 patients, 25 (11.4%) did not have FDG uptake in the tumor. The 219 cases with breast cancer were divided into two groups based on the presence of FDG uptake in the primary tumor. The present univariate analysis revealed that histology, small invasive tumor size, high estrogen receptor (ER) or progesterone receptor (PgR) expression, low nuclear grade and absence of lymph node metastasis were significantly associated with negative FDG uptake in the primary tumor. On the other hand, the size of ductal spread was not significantly different between the two groups. Multivariate analysis revealed that small-size tumor invasion and lower nuclear grade were statistically significant. Among the 25 cases without FDG uptake, there was no recurrent disease in spite of there being no case that underwent chemotherapy, while 4 cases among the 194 cases with FDG uptake had disease recurrence. Our findings imply that preoperative FDG negativity in primary breast cancer is effective in predicting better prognosis, but is less effective in predicting ductal spread. Cases without FDG uptake in the primary tumor may have a lower risk of recurrent disease and may be able to safely avoid adjuvant chemotherapy.

Clinical Significance of 18F-FDG-PET in Invasive Lobular Carcinoma.

The diagnostic utility of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for breast cancer is controversial. The histological type or tumor size of breast cancer has been reported to be associated with a greater likelihood of positive FDG uptake. Compared to invasive ductal carcinomas (IDCs), invasive lobular carcinomas (ILCs) have a lower level of FDG uptake and are detected at a significantly lower sensitivity. The role of preoperative FDG-PET for ILCs may, thus, be limited. Few data evaluating the significance of FDG-PET in ILCs are available. Here, we evaluated the clinical significance of FDG-PET for ILC patients. We retrospectively investigated the cases of 196 consecutive patients with primary breast cancer who were diagnosed as having ILC (n=15) or IDC (n=181) and underwent FDG-PET preoperatively. Fifteen (7.7%) of patients were histopathologically diagnosed as ILC. A univariate analysis revealed that tumor size, extent of tumor, estrogen receptor (ER) expression and progesterone receptor (PgR) expression were significantly different between the ILC and IDC groups. The maximum standardized uptake value (SUVmax) values of the primary tumors were not significantly different between the two groups but, regardless of the larger size of tumor or ductal spread, the SUVmax was relatively lower in the ILC group compared to the IDC group. The tumors in two ILC cases showed no FDG uptake. Among the ILC cases, there were linear associations between SUVmax and tumor size and between SUVmax and the nuclear grade by Pearson correlation (r=0.447, p=0.048 and r=0.519, p=0.024, respectively). Our findings imply that the preoperative FDG uptake in ILC may be reflective of the tumor size and the nuclear grade of the tumor. FDG uptake may be useful and predictive of aggressive features or prognosis in ILC patients.

Co-expressed type of ER and HER2 protein as a predictive factor in determining resistance to antiestrogen therapy in patients with ER-positive and HER2-positive breast cancer.

The purpose of this study was to analyze whether inter-site variation types on estrogen receptor (ER) and HER2 expression may be a predictive factor for evaluating the effectiveness of endocrine therapy in patients with ER-positive and HER2-positive breast cancer. A total of 366 consecutive women with invasive breast cancer who had undergone curative surgical treatment between 1996 and 2001 were included in this study. ER status was evaluated using the Allred score and HER-2 status was evaluated according to the HercepTest. In ER-positive and HER2-positive tumors, the expression of ER and HER2 was described as the co-expressed type or the differently expressed type using double staining with ER and HER2. Of the 366 patients, 249 (68.1%) were positive for ER and 74 (20.2%) were positive for HER2. ER-positive and HER2-negative tumors were found in 221 patients (60.4%), ER-negative and HER2-negative in 71 (19.4%), ER-negative and HER-2-positive in 46 (12.6%), and ER-positive and HER2-positive in 28 (7.7%). HER2 status was inversely correlated (p<0.01) with ER status. In ER-positive tumors, an inverse correlation between ER and HER2 was also observed. The co-expressed type was found in 10 patients, and the differently expressed type was found in 18. There was no difference in tumor size and nodal involvement between the two types. There was no significant difference in disease-free survival between patients with the co-expressed type tumor and the differently expressed type tumor. In patients with the differently expressed type tumor, those who received antiestrogen therapy showed a significantly better disease-free survival rate than those who did not receive antiestrogen therapy. As for patients with the co-expressed type of tumor, no significant difference in disease-free survival was observed between patients with and without antiestrogen treatment. The present study suggests that the co-expressed type of tumour might be a resistant factor to antiestrogen therapy in ER-positive and HER2-positive breast cancer.

Local control by breast-conserving surgery with nipple resection.

Local control was compared between patients who had undergone breast-conserving therapy with and without nipple resection. We explored whether there was any difference in local control between the two treatment methods for patients with early breast cancer. A total of 333 women with breast cancer, who had undergone breast-conserving therapy between 1991 and 2002, were included in this study. Surgery consisted of a wide local excision of the primary tumor with a 2-cm free margin as the minimum distance. When the tumor was located under the nipple or close to the nipple, breast-conserving surgery with nipple resection was selected. A total of 320 patients received breast-conserving surgery without nipple resection and radiation therapy (BCT) and 13 patients breast-conserving surgery with nipple resection and radiation therapy (BCT-NR). There were no significant differences in age, tumor size, nodal status, clinical stage, ER status, histological type or surgical margin status between the two groups. The surgical margin was positive in 55 (17.2%) out of 320 patients in the BCT group and in one (7.7%) out of 13 patients in the BCT-NR group. There was no significant difference in the breast-free survival between the two groups. In conclusion, breast-conserving surgery with nipple resection and radiation therapy may be the treatment of choice for early breast cancer patients with the tumor located under the nipple or very close to the areola.

Two cases of breast cancer with cartilaginous and osseous metaplasia.

Invasive breast cancer (IBC) with cartilaginous or osseous metaplasia is rare. Here we report two cases of this unusual variation. Case 1: The patient was a 33-year-old woman with a right breast tumor, 2.2 cm in size. Mammograms (MMG) presented no specific findings, but ultrasound (US) showed a cystic-like lesion. Excisional biopsy confirmed IBC with cartilaginous and osseous metaplasia. Biopsy was followed with a modified radical mastectomy. One lymph node was positive, and both estrogen receptor (ER) and progesterone receptor (PgR) were negative. Case 2: The patient was a 43-year-old woman with a left breast tumor, 4.2 cm in size. MMGs presented no findings but US showed an irregular shaped, low-echoic area, suggesting malignancy. Core needle biopsy confirmed IBC with cartilaginous metaplasia. A total adenectomy and lymph node dissection with breast reconstruction using a lattisimus dorsi muscle flap were performed. Two of 18 lymph nodes were positive for metastasis and both ER and PgR were negative. IBC with cartilaginous or osseus metaplasia seem to be divided into two types pathologically, with or without intervening spindle cells, which is related to the prognosis. Matrix producing carcinoma (MPC) has no intervening spindle cells and a better prognosis than other types, however, MPC has been reported to have the same prognosis as ordinary breast cancer after for adjusting its stage. Our two cases were MPC's and no recurrence has been detected 5 and 3 years from the initial therapy, respectively.

A Case of Type 2 Amiodarone-Induced Thyrotoxicosis That Underwent Total Thyroidectomy under High-Dose Steroid Administration.

Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT)) and destructive thyroiditis (type 2 AIT). We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone), the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration.

Immunohistochemical double staining with estrogen receptor and HER2 on primary breast cancer.

Immunohistochemical double staining with estrogen receptor (ER) and epidermal growth factor receptor 2 (HER2) was conducted in tissue sample of 125 women with invasive breast cancer. The age at the time of surgery ranged from 28 to 82 years. The tumor size was 2 cm or less in 42 patients and larger than 2 cm in 83. Axillary lymph node status was positive in 53 patients and negative in 72. Estrogen receptor (ER) which was measured using enzyme immunoassay (EIA) was positive in 67 patients, negative in 50 and unknown in 8. Of the 125 patients evaluated, 83 (66.4%) were immunohistochemically positive for ER. ER by immunohistochemistry (IHC) (ER-IHC) was significantly (p<0.01) correlated with ER by EIA (ER-EIA). ER-EIA values in ER-IHC scores were 1.4 fmol/mg protein in score 0, 0.0 in score 1, 19.0 in score 3, 21.2 in score 4, 12.2 in score 5, 17.6 in score 6, 30.0 in score 7 and 114.8 in score 8. ER-EIA values in ER-IHC-score 8 were significantly higher than in scores 0, 2, 3, 4, 5, 6 and 7. Of the 125 patients, 35 (28%) were immunohistologically positive for HER2. HER2 expression was inversely correlated with ER expression. When evaluated even in ER-positive patients, HER2 overexpression was associated with lower ER levels. In this study, we conducted immunohistochemical double staining with ER and HER2, and demonstrated that low ER levels might be one factor in the relative resistance of HER2-positive and ER-positive tumors to hormonal therapy.

Long-term suppression of lymphangitic lung metastasis from breast cancer using biweekly docetaxel: a case report.

A 45-year-old woman underwent a modified radical mastectomy for right breast cancer in July 1996. As lymph node metastases were quite advanced, chemotherapy was started with anthracyclines. Four years after surgery, cough and dyspnea appeared. Chest radiograph and CT showed reticular shadows bilaterally and slight pleural effusion, suggesting lymphangitic lung metastasis of breast cancer. Biweekly intravenous docetaxel (TXT,45 mg/m2) was initiated. Four courses of TXT ameliorated her complaints and radiographic findings. A total of 30 continuous courses of TXT suppressed disease exacerbation for 18 months until new lesions manifested in January 2002. The main side effects were grade 2 leukopenia and alopecia. This case report describes a patient with long-term suppression of lymphangitic lung metastasis of breast cancer using biweekly TXT without severe side effects or worsening quality of life.