Yukiko Nagashima

Luminal A and luminal B (HER2 negative) subtypes of breast cancer consist of a mixture of tumors with different genotype

BackgroundThe St Gallen International Expert Consensus 2011 has proposed a new classification system for breast cancer. The purpose of this study was to elucidate the relationship between the breast cancer subtypes determined by the new classification system and genomic characteristics.MethodsInvasive breast cancers (n = 363) were immunohistochemically classified as follows: 111 (30.6%) as luminal A, 95 (26.2%) as luminal B (HER2 negative), 69 (19.0%) as luminal B (HER2 positive), 41 (11.3%) as HER2, and 47 (12.9%) as basal-like subtypes.ResultsThe high expression of Ki-67 antigen was detected in 236 tumors; no cases of luminal A subtype showed high expression of the Ki-67 antigen, but more than 85% of tumors of the other subtypes showed high expression. In addition, DNA ploidy and chromosomal instability (CIN) were assessed using imaging cytometry and FISH, respectively. In this series, 336 (92.6%) tumors consisted of 129 diploid/CIN- and 207 aneuploid/CIN + tumors. Diploid/CIN- and aneuploid/CIN+ features were detected in 64.9% and 27.9% of luminal A, 41.1% and 49.5% of luminal B (HER2-), 11.6% and 81.2% of luminal B (HER2+), 4.9% and 90.2% of HER2, and 17.0% and 76.6% of basal-like subtypes, respectively. Unlike the luminal B (HER2+), HER2 and basal-like subtypes, the luminal A and luminal B (HER2-) subtypes were heterogeneous in terms of DNA ploidy and CIN.ConclusionsIt is reasonable to propose that the luminal A and luminal B (HER2-) subtypes should be further divided into two subgroups, diploid/CIN- and aneuploid/CIN+, based on their underlying genomic status.

Detection of autoantibodies against cyclophilin A and triosephosphate isomerase in sera from breast cancer patients by proteomic analysis.

Much interest is presently being shown toward identifying markers for the detection of breast cancer. To detect autoantibodies that could represent diagnostic markers for breast cancer, we comprehensively analyzed serum autoantibodies showing immunoreactivity to proteins in tumor tissues of breast cancer. Tumor tissues were obtained from 40 patients with breast cancer, along with sera from 30 other patients with breast cancer and 22 healthy donors. Proteins from tumor tissues were separated by 2‐DE. After blotting onto PVDF membranes, tissue proteins were immunoblotted with sera from patients or healthy donors. By comparing each immunoblot pattern, three immunoreactive spots displayed stronger staining intensity with patient sera than with sera from healthy donors. The matched protein spots on 2‐DE gels were digested and used for LC‐MS/MS analysis, and identified as cyclophilin A (peptidyl‐prolyl cis‐trans isomerase A), triosephosphate isomerase and ubiquitin‐conjugating enzyme E2N. Immunoblot analysis was then performed using commercially available purified proteins, confirming the specificity of anti‐cyclophilin A and anti‐triosephosphate isomerase antibodies in sera from patients.

Evaluation of host quality of life and immune function in breast cancer patients treated with combination of adjuvant chemotherapy and oral administration of Lentinula edodes mycelia extract

Purpose Anthracycline-based chemotherapies for breast cancer are well known to have adverse effects and can also negatively affect host immune function. There is therefore a necessity for an adjuvant that maintains the quality of life (QOL) and immune function of cancer patients receiving anthracycline-based chemotherapies. Patients and methods The present study investigated the effectiveness of the concomitant use of Lentinula edodes mycelia extract (LEM), an oral immunomodulator, with FEC75 (5-fluorouracil + epirubicin + cyclophosphamide) therapy on host QOL and immune function in breast cancer patients with nodal metastases. Ten breast cancer patients with nodal metastases receiving surgery were enrolled in this study. Treatment with 5-fluorouracil (500 mg/m2), epirubicin (75 mg/m2), and cyclophosphamide (500 mg/m2) was performed every 21 days for two courses, and LEM (1800 mg/day by mouth) was administered during the second course. Results In the first course, hematological toxicity was observed and host QOL and immune function were exacerbated. In the second course, however, the number of white blood cells and lymphocytes did not decrease and host QOL was maintained. Furthermore, the cytotoxic activities of natural killer (NK) and lymphokine-activated killer cells and the proportion of activated NK and NK T-cells in lymphocytes were maintained in the second course. Conclusion It has been suggested that the concomitant use of LEM with FEC75 therapy can maintain host QOL and immune function, and offer important implications for an application of LEM as a useful oral adjuvant to anthracycline-based chemotherapies.

Sentinel lymph node detection in breast cancer patients by real-time virtual sonography constructed with three-dimensional computed tomography-lymphography.

Abstract #1026 Background: Ultrasonography (US) is one tool for preoperative diagnosis of lymph node metastases in breast cancer. However, US cannot detect true sentinel lymph nodes (SLNs).
 Methods: We identified SLNs in 60 clinically node-negative breast cancer patients using a real-time virtual sonography (RVS) system to display in real time a virtual multi-planar reconstruction obtained from computed tomography (CT) volume data corresponding to the same cross-sectional image from US. CT volume data were obtained from our original three-dimensional CT lymphography (3DCT-LG), which accurately detects SLNs in breast cancer. SLN metastases were assessed by shape and visibility of the hilum. All patients underwent SLN biopsy and SLN metastases were examined pathologically.
 Results: In all 60 patients, we were able to detect the same SLNs visualized by 3DCT-LG. Suspicious SLN metastases were identified in 7 of the 60 patients, and 4 of 7 patients were pathologically positive. Positive predictive value was 57%. The remaining 53 patients displayed non-suspect SLNs in which absence of metastasis from the SLN was confirmed histologically. Overall accuracy was 95%.
 Conclusions: This is a first attempt at preoperatively identifying SLNs using US guided by the RVS system in breast cancer patients. Although evaluation of SLN metastases was unsatisfactory, this method may be useful for preoperative fine-needle aspiration cytology for diagnosis of SLN metastases. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1026.