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Summary Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m2) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings. Electronic supplementary material The online version of this article (doi:10.1007/s10637-017-0486-4) contains supplementary material, which is available to authorized users.

We developed a prototype photon-counting mammography unit with a cadmium zinc telluride detector, which provides a new type of image with physical analysis parameters. Using the X-ray attenuation information obtained from this device, we examined the ability of this technique in discriminating substances and estimating their compositions. To estimate the substance compositions, we used resected breast tissues immediately after a surgical operation for invasive carcinoma of no special type, and used phantoms to reproduce mammary glands and adipose tissue. In our system, the spectrum penetrating the substance was measured with three energy bins in each pixel. The products of linear-attenuation coefficient and thicknesses for each bin were calculated. Using these three values, the scatterplots displaying all the values calculated from each pixel inside the region of interest (ROI) on the image were created. The scatterplot displaying only gravity values calculated for each ROI on the image was created for evaluating the separation of plot points to discriminate between different substance compositions. The gravity points placed on the malignant tumor tissue were plotted separately from those on the normal tissue. Furthermore, a fusion image was created by overlapping an X-ray image and values of this scatterplot points represented on a 10-step color scale. The fusion image was highlighting the differences in substance compositions using color tone, such as malignant tumor or mammary gland tissue, by adjusting the color scale level.

It is often necessary to modify the dose or schedule of eribulin mesilate (Eri) because of adverse events. Therefore, we retrospectively investigated the optimal approach for Eri dose adjustment and/or dosage interval adjustment. Patients who received Eri at the institutions affiliated with the Division of Oncology of the Aichi Prefectural Society of Hospital Pharmacists between July 2011 and November 2013 were enrolled in this study. We compared the group that underwent dose reduction without changes to their dosage interval (dose reduction group) with the group that had a change in their dosage interval (dose-interval prolongation group). The primary end-point was time to treatment failure (TTF), and the secondary end-points were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and adverse events. The TTF and OS of the dose reduction group were approximately two times longer than those of the dose-interval prolongation group. In addition, the dose reduction group had significantly improved ORR and CBR, which together indicate an antitumor effect (p=0.013 and 0.002, respectively). Although peripheral neuropathy occurred significantly more frequently in the patients in the dose reduction group (p=0.026), it was grade 1 and controllable in most of the cases. There were no differences in the occurrence of other adverse effects between the two groups. Therefore, we suggest that dose reduction with maintenance of the dosage interval is the preferred treatment approach in cases where Eri dose or schedule modification is necessary.

Prevention of chemotherapy-induced nausea and vomiting (CINV) is of great importance for the completion of multiple cycles of cancer chemotherapy. Palonosetron is a second-generation 5-HT(3) receptor antagonist with proven efficacy for both acute and delayed CINV. This study was designed to assess the safety and efficacy of 0.75 mg palonosetron in repeated cycles of highly emetogenic chemotherapy or anthracycline-cyclophosphamide combination (AC/EC).We gave 0.75 mg palonosetron to 538 patients 30 min prior to ≥ 50 mg/m(2) cisplatin or AC/EC on day 1. Prophylactic dexamethasone was administered on days 1-3. The primary endpoint was the incidence rate of adverse events (AEs). The secondary endpoint was complete response rate (CR, defined as no emesis and no rescue medication) throughout the study period.Treatment-related AEs were seen in 44% (237 of 538 patients). Serious AEs were seen in 4% (23 of 538 patients), all considered unrelated or unlikely to be related to palonosetron. Only one patient discontinued the study due to a treatment-related AE. No trend toward worsening of AEs was observed in subsequent cycles of chemotherapy. Complete response rates were maintained throughout repeated cycles.The extraordinary safety profile and maintenance of efficacy of 0.75 mg palonosetron combined with dexamethasone were demonstrated throughout repeated chemotherapy cycles.

Background: Invasive micropapillary carcinoma (IMP) of the breast is uncommon and has only recently been characterized. Knowing the cytological appearance of IMP is important to enable early diagnosis by fine needle aspiration cytology (FNAC). We describe a case of IMP diagnosed by preoperative FNAC. Case: A 48-year-old menopausal woman presented in 2003 with a mass in her left breast. Mammogram and ultrasound findings indicated that the tumor was malignant. Cytological examination showed papillary clusters of hyperchromatic cells with irregular and crowded nuclei, but lacking papillary cores. No myoepithelial cells were seen. Based on the cytological findings, invasive micropapillary carcinoma was diagnosed. Microscopic findings showed cancer cells with moderate atypia in abundant micropapillary cancer nests without a fibrovascular core. These cancer nests were morula-like, surrounded by empty, clear spaces lined with delicate strands of fibrocollagenous stroma. The polarity of each cancer nest was reversed, with the secretion border facing fibrocollagenous stroma. These pathological features occupied the invasive part of the primary tumor. Conclusion: The cytologic features of IMP are distinctive and correlate with histology. FNAC of IMP is important role to confirm the diagnosis.

Background: While Snail is a zinc-finger transcription factor that triggers the epithelialmesenchymal transition, it has also been reported to be indirectly regulated by estrogen receptor a (ERa) and to be involved in the transcriptional repression of the aromatase gene. The aim of the present study was to examine the role of Snail expression in node-negative invasive ductal carcinomas. Methods: We analyzed Snail mRNA expression levels in 86 node-negative invasive ductal carcinomas by real-time quantitative RT–PCR and studied whether Snail mRNA expression correlates with clinicopathological factors. Results:No correlationwas found betweenSnailmRNA expressionandERaprotein expression levels. However, we observed that none of the 34 patients showing low Snail mRNA expression developed distant metastasis while 6 of 52 (12%) showing high expression of Snail mRNA did. The level of Snail mRNA expression was not found to be significantly correlated with clinicopathological factors. No inverse correlation was found between the Snail and aromatase mRNA expression levels in our series. Conclusion: Our data show that low expression of Snail mRNA is a good prognostic factor in node-negative invasive ductal carcinomas. Snail expression is suggested to be involved in distant metastasis in node-negative invasive ductal carcinomas.

A vertical-cavity surface-emitting laser (VCSEL) was fabricated using a in situ reflectance monitor by molecular beam epitaxy (MBE). Both the center wavelength of the stop band of the distributed Bragg reflector (DBR) and the resonant wavelength of the optical cavity were successfully controlled using the monitor. However, these wavelengths shifted with decreasing substrate temperature after the growth, which could be reasonably explained by the temperature dependence of refractive index. Therefore, it is necessary to set a target wavelength at a growth temperature, considering the change. The desirable laser performance of the VCSEL fabricated from the wafer indicates marked increases in the controllability and reproducibility of growth with the aid of the in situ reflectance monitor. Since it can directly measure the optical properties of the grown layers, the reflectance monitor greatly helps in the fabrication of a structure with the designed optical performance.

A cohort study for Caucasians aged 65 years or older demonstrated a marked breast cancer risk reduction for those with the CC genotype of transforming growth factor B1 (TGF B1) T29C polymorphism. This is a prevalent case-control study to examine the reported risk reduction for Japanese women.A total of 232 histologically diagnosed breast cancer patients who visited Aichi Cancer Center Hospital between June 1999 and March 2000 were enrolled. The controls were 172 female outpatients without cancer at the same hospital. DNA was extracted from peripheral blood, and TGF B1 genotype was determined by PCR-CTPP.The genotype frequency was 23.7% for TT, 49.2% for TC, and 27.1% for CC among controls, and 28.9%, 46.1%, and 25.0%, respectively, among cases. Age-adjusted odds ratio (OR) relative to the TT genotype was 0.81 (95% confidence interval, 0.50-1.31) for the TC genotype and 0.77 (0.45-1.34) for the CC genotype. For premenopausal women, the CC genotype was significantly associated with reduced risk of breast cancer in comparison with the TT genotype (OR=0.45, 0.20-0.98). The association was not observed for postmenopausal women (OR=1.40, 0.64-3.08).The present study showed risk reduction for Japanese premenopausal women with the CC genotype, but not for postmenopausal Japanese women.

Objective: The present case-control study aimed to examine the associations between breast cancer risk and three functional polymorphisms (Interleukin (IL) –1A C-889T, IL-1B C-31T and IL-1RN 86-bp variable number tandem repeat) related to expression of IL-1, which combines estrogen receptor. Methods: Cases were 231 patients with breast cancer who had been diagnosed 1 month to 6 years before their enrollment in 1999–2000 at Aichi Cancer Center Hospital. Controls were 186 non-cancer outpatients recruited during the same period at the digestive tract, breast surgery and gynecology clinics. Results: There were no differences in the genotype distributions of the IL-1A and IL-1RN polymorphisms, but individuals harboring a IL-1B C-31T T allele (high expression allele) were less frequent among cases (74.3%) than among controls (84.9%). The age-adjusted odds ratio (OR) relative to CC genotype was 0.52 (95% confidence interval, 0.30–0.88) for CT genotype, 0.58 (0.32–1.02) for TT genotype and 0.54 (0.33–0.90) for CT/TT genotype. Subgroup analysis showed that the preventive effect was significantly stronger for postmenopausal women than for premenopausal women (interaction 0.30, 0.11–0.84). Conclusions: Although this is the first report on the association between breast cancer risk and IL-1B C-31T, the observed association seems plausible in a biological sense.

The identification rate of sentinel lymph nodes (SLNs) is variable because numerous different methods employing different tracers have been used for sentinel lymph node detection. The aim of this study was to determine the optimal technique for sentinel lymph node biopsy (SLNB).From May 1999 to December 2001, SLNB was performed for 376 patients with T1-3 and N0-1 primary breast cancer using blue dye alone, radioisotope (RI) alone and combination of RI and blue dye. Two hundred sixty-eight patients underwent SLNB using blue dye alone. They were divided into 4 groups (Group A: n=50; peritumoral injection, Group B: n=83; the first half to receive subareolar injection, Group C: n=83; the second half to receive subareolar injection, and Group D: n=52; small incision according to an axillary skin landmark). One hundred eight patients underwent SLNB using RI. Tin colloid was used in 49 cases (Tin Colloid Group) and phytate in 59 cases (Phytate Group). Among them, 29 patients underwent injection of RI alone and 79 patients received a combination of RI and blue dye.The identification rates of SLN using blue dye alone were 60%, 82%, 92% and 79% in Groups A, B, C and D, respectively. The identification rates of SLN in patients receiving RI alone and in those receiving combination of RI and blue dye were 40% and 89%, respectively, in Tin Colloid Group, and 92% and 94%, respectively, in Phytate Group.When using blue dye alone, subareolar injection provided a better identification rate than peritumoral injection. The combination of peritumoral phytate and subareolar blue dye provided the best identification rate (94%) in all the groups. The combination of intraparenchymal phytate and subareolar blue dye was the most efficient technique for sentinel node biopsy in breast cancer patients.

Experimental studies suggest various features of anticancer activity of green tea including inhibitory effect of tumor invasion and metastasis. This study was conducted to examine the association between regular green tea consumption prior to diagnosis and subsequent risk of breast cancer recurrence. The Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) was started in 1988, in which information on lifestyle has routinely been collected from all first-visit outpatients by questionnaire. A total of 1160 new surgical cases of female invasive breast cancers with HERPACC information diagnosed between June 1990 and August 1998 were followed up through December 1999, and the risk (hazard ratio: HR) of recurrence was assessed with reference to daily green tea consumption using a Cox proportional hazard model. During 5264 person-years of follow-up, 133 subjects (12%) were documented to suffer recurrence of breast cancer. A decreased HR for recurrence adjusted for stage was observed with consumption of three or more daily cups of green tea (HR=0.69, 95% confidence interval (95%CI)=0.47-1.00). Particularly in stage I, the HR was decreased statistically significantly (HR=0.43, 95%CI=0.22-0.84). A similar tendency was observed for stage II subjects, but was not present among more advanced stages. Although careful interpretation is needed, these results suggest the possibility that regular green tea consumption may be preventive against recurrence of breast cancer in early stage cases.

Background. Catechol-O-methyltransferase (COMT) inactivates the estradiol metabolites, 2-hydroxy estradiol and 4-hydroxy estradiol. To date, three studies in Caucasians and one study in Chinese have been conducted to determine the association with breast cancer risk of a functional polymorphism (G-to-A, Val158Met) of this enzyme, but the results were inconsistent. In order to examine the impact of this polymorphism on breast cancer risk in Japan, a case-control study was conducted, at Aichi Cancer Center Hospital. Methods. The cases were 150 patients with histologically confirmed breast cancer who had been diagnosed within 4 years before enrollment at this hospital. The controls were 165 non-cancer patients, mainly from the gastroenterology and breast surgery clinics at the hospital. COMT-H (Val) is the wild-type allele, with high enzyme activity, while the COMT-L (Met) allele has low activity. Genotyping was conducted by a polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. Results. The allele frequency of COMT-L was 36.0% for cases and 33.0% for controls. Age-adjusted odds ratios relative to the COMT-HH genotype were 1.46 (95% confidence interval [CI], 0.90–2.36) for COMT-HL, and 0.99 (95% CI, 0.49–2.02) for the COMT-LL genotype. Significant odds ratios were not observed for any subgroup stratified by menopausal status, age at menarche, age at birth of first child, body mass index, and breast cancer history of mother and/or sister(s). Conclusion. The present study suggested that any association of the COMT polymorphism with breast cancer risk is limited in Japanese.

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5' promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and 0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother / sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5' promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.

Recently there have been several reports on the effectiveness of combination chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA) for treating recurrent breast cancer. We report a case in which treatment of local recurrence and lung metastases responded was remarkably effective by this combination chemotherapy. A 45-year-old woman underwent modified radical mastectomy for left breast cancer (T2N0M0) three years previously. Involvement of a left supraclavicular lymph node (ScLN) and multiple lung metastases were revealed 2 years and 6 months after the operation. First, we opted for systemic endocrine therapy with local irradiation for the lung metastases and ScLN. However the lung metastases were found to have increased on chest x-ray 2 months after treatment, showing progressive disease (PD). A locally recurrent new lesion sized 2 x 2 cm had also developed. Thus, we changed the treatment to combination chemotherapy with 5'-DFUR 800 mg/body and oral CPA 100 mg/body once a day. The lung metastases had disappeared on chest x-ray and the local recurrence was not palpable after 7 weeks of the new treatment. Thymidine phosphorylase (dThdPase) immunostaining of the primary tumor was strongly positive in almost all cancer cells. We discuss the mechanism of the increased efficacy of combination chemotherapy with 5'-DFUR and CPA.

Objective: FSK0808 is a filgrastim biosimilar. This study assessed the efficacy and safety of FSK0808 in patients with breast cancer. Methods: One hundred and four breast cancer patients undergoing chemotherapy were enrolled in the study. FSK0808 was used to treat the neutropenia experienced by the patients in the course of their chemotherapy. Efficacy was evaluated by the recovery of absolute neutrophil count following FSK0808 administration based on the duration of neutropenia in patients who received pre- or postoperative chemotherapy containing fluorouracil, epirubicin and cyclophosphamide. Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events version 3.0. The incidence of febrile neutropenia and generation of an anti-granulocyte colony-stimulating factor antibody were also evaluated. Results: The average duration of neutropenia in Cycle 2 was 2.2 days with a standard deviation of 1.5 days. The upper limit of the 97.5% one-sided confidence interval was 2.5 days and was confirmed not to exceed 3.0 days, which was defined as the threshold value of absolute neutrophil count recovery. The incidence of febrile neutropenia across all treatment cycles was 34.6%. Observed adverse drug reactions with an incidence of .5% were back pain (60.6%), bone pain (9.6%), alanine aminotransferase increase (8.7%), aspartate aminotransferase increase (5.8%) and arthralgia (5.8%). Production of the anti-granulocyte colony-stimulating factor antibody was not observed in any patient during the study. Conclusions: FSK0808 was safe and well tolerated in breast cancer patients undergoing chemotherapy and effectively stimulated neutrophil recovery.

We evaluated the efficacy and safety of sequential therapy with trastuzumab monotherapy (H-mono) followed by H plus docetaxel (D) after disease progression (H → H + D) versus combination therapy with H + D as first-line therapy. Patients with human epidermal growth factor receptor type 2 (HER2)-positive metastatic breast cancer (MBC) and left ventricular ejection fraction >50% were randomly assigned to either (a) H → H + D [H, once weekly 2 mg/kg (loading dose, 4 mg/kg); D, once every 3 weeks 60 mg/m2] or (b) H + D. Primary endpoints were progression-free survival (PFS) for the H-mono stage of the H → H + D group and H + D group and overall survival (OS) for both groups. Secondary endpoints were overall response rate, time to treatment failure, second PFS and safety. The planned number of patients was 160 patients in total. Of 112 patients enrolled, 107 were eligible. After 112 patients were enrolled, the Independent Data Monitoring Committee recommended stopping enrollment because PFS and OS were greater in the H + D group than the H → H + D group. Median PFS was 445 days in the H + D group versus 114 days for H-mono in the H → H + D group [hazard ratio (HR), 4.24; P < 0.01]. OS was significantly longer in the H + D group (HR, 2.72; P = 0.04). H + D therapy is significantly superior to H → H + D therapy as first-line therapy in patients with HER2-positive MBC, especially in terms of OS.

9594 Background: While opioid analgesics play a central role in managing cancer pain, opioid-induced constipation (OIC) is one of the most common side effects. Naldemedine is a novel peripherally-acting μ-opioid receptor antagonist (PAMORA) being developed to treat OIC. Methods: This study assessed naldemedine doses of 0.1, 0.2, or 0.4 mg once-daily (QD) for 2 weeks in cancer patients with OIC. Eligibility criteria included: regular opioid use for ≥ 2 weeks, ≤ 5 spontaneous bowel movements (SBMs) during a 14-day screening period despite laxative use. The primary endpoint was the change from baseline in frequency of SBM/week during the 2-week treatment period. The SBM responder rate, defined as ≥ 3 SBMs/week and an increase from baseline of ≥ 1 SBM/week, was a secondary endpoint. Safety assessments included adverse events (AEs), Clinical Opiate Withdrawal Scale (COWS) questionnaire and 11-point Numerical Rating Scale (NRS) pain questionnaire. Patients scored bowel movement (BM) consistency using the Bristo...

We have reported the Diagnostic Guidelines for Non-Mass Image-Forming Lesions. These have been discussed in the subcommittee of the Japan Association of Breast and Thyroid Sonology (JABTS) and the Japan Society of Ultrasonics in Medicine.

Many aspects of internal echoes of mass image-forming breast lesions have been discussed. These points, as well as other themes, should be documented or corrected through further investigation in wide clinical practice.

76 Diagnostic Criteria for Breast Lesions has been widely used since its release in 1988 by the Japan Society of Ultrasonics in Medicine (JSUM). However, improved diagnostic procedures and new data led to a growing desire for revisions to this publication. Prompted by that growing demand, in 2000 the JSUM set up a Subcommittee on Diagnostic Criteria for Breast Diseases (SCDCBD-JSUM; chairman, Ei Ueno), thus launching a study of new diagnostic guidelines for these diseases. The subcommittee classified breast diseases into two categories, mass imageforming and non-mass image-forming lesions as shown on ultrasonograms, and won approval of its classification for mass image-forming lesions as part of the revision process. These revisions were published in the Journal of Medical Ultrasonics and JSUM members have been invited to comment. The Japan Association of Breast and Thyroid Sonology’s Committee on Diagnostic Criteria for Breast Diseases (CDCBDJABTS; chairman, Tokiko Endo) also engaged in a study of the terminology that provides the basis for these classifications. Details of these studies are elaborated here.

The association between breast cancer risk and genetic polymorphisms of p53 at codon 72 (Arg72Pro) has been investigated by several studies, but the results are not consistent. The aim of this case-control study conducted in Nagoya, Japan, was to reconfirm the results of prior studies of polymorphisms of p53 Arg72Pro, and to test if polymorphisms of p73 G4C14-to-A4T14 at exon 2 (G4A) were also associated with breast cancer risk.The cases were 200 breast cancer patients who visited Aichi Cancer Center Hospital. The controls were 282 local citizens who underwent a health check-up. All cases and controls were recruited from Chubu Japan. Genotyping was carried out by polymerase chain reaction with confronting two-pair primers.The p53 genotype distribution was 40.4% for Arg72 homozygous, 48.9% for heterozygous, and 10.7% for Pro72 homozygous in controls, and 32.0%, 50.0%, and 18.0% in cases, respectively. A comparison between cases and controls indicated a significantly increased risk for Pro72 homozygosity in cases (odds ratio=2.14; 95% confidence interval=1.21-3.79). The genotypic frequencies for p73 G4A were 54.3% for G/G, 39.7% for G/A, and 6.0% for A/A in controls; and 59.0%, 32.0%, and 9.0% in cases, respectively. There were no significant differences in p73 G4A frequency between cases and controls.This study implies an association of breast cancer risk with the p53 polymorphism Arg72Pro, but not with p73 G4A.

Extracellular matrix-degrading proteinases secreted by malignant tumor cells have been thought to play an essential role in the processes of invasion and metastasis. However, existence and localization of gelatinase activity in breast cancer tissues have not been clarified.We developed a novel film for highly reproducible detection and the localization of gelatinolytic activity. This film has a gelatin layer with a constant thickness 7 microm, and adequate crosslinking to control the speed of degradation by proteases. Cryosections of several breast cancer tissues were put on this gelatin film and incubated for 16 hrs at 37 degrees C. After staining with ponceau 3R dye, the digested area was evaluated under light microscopy.Digestion of gelatin was detected in more than 90%of breast cancer specimens, although it varied in degree and area for each case. In most cases, the gelatinolytic activity was located within cancer nests, and was not detected in stromal cells surrounding cancer cells. The gelatinolytic activity was inhibited by 1,10-phenanthroline, an inhibitor of matrix metalloproteinases (MMPs).In this study, the localization of net MMP activity was confirmed in breast cancer nest using film in situ zymography. Detailed analysis on the relationship between the strength or distribution of MMP activity and malignancy are anticipated in the future.

PURPOSE: To evaluate the CAD system for screening mammograms. MATERIALS AND METHODS: Mammograms of patients with asymptomatic breast cancerwere examined retrospectively. A total of 260 screening mammograms from 65 patients (bilateral cranio-caudal and medio-lateral-oblique views from each) were tested by using the CAD system (ImageChecker M1000 system, R2 Technology, Los Altos, CA, USA). Results: With 0.58 microcalcifications marks/film and 0.20 mass marks/film set as the false positive rate, 100% of microcalcifications cases and 79% of mass cases were detected correctly. Conclusion: The CAD system has the potential to become a second reader. Further developments are expected to improve the accuracy of detection of mass lesions

Background The involvement of β2-adrenergic receptor (ADRB2) and β3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan.