Hisanori Kawamoto

Analysis of Cdc2 and cyclin D1 expression in breast cancer by immunoblotting

Cyclins and cyclin-dependent kinases may reflect the status of cell proliferation in cancer tissues. The authors sought to determine whether cdc2 and cyclin D1 are expressed in breast cancer and are useful as prognostic factors. Accumulation of cdc2 and cyclin D1 proteins was examined in 88 cases of breast cancer using immunoblotting techniques and correlations with clinicopathological factors and prognoses were investigated. Cdc2 and cyclin D1 proteins were observed in 27.3% and 75.0% of breast cancers studied, respectively. The incidence of lymph node metastasis was significantly high in cdc2/cyclin D1-double positive group and low in double negative group. On the other hand, the incidence of estrogen receptor (ER) negative cases was significantly higher in the cdc2-positive/cyclin D1-negative group. Relapse-free survival times of cdc2-positive cases were significantly shorter than those of cdc2-negative cases. The relapse-free survival times of cyclin D1-positive cases also tended to be poorer than those of cyclin D1-negative cases. Multivariate analyses revealed cdc2 as the second most significant of the prognostic variables, following lymph node status. The three-year relapse-free survival rate of cdc2/cyclin D1-double positive cases was 58.9%, whereas that of cdc2/cyclin D1-double negative cases was 100%. Cdc2 and cyclin D1 represent the status of cell proliferation in breast cancer, and may be useful in breast cancer assessment.

Microcalcifications of Breast Tissue: Appearance on Synchrotron Radiation Imaging with 6-μm Resolution

OBJECTIVE The purpose of this study was to use synchrotron radiation imaging with 6-microm resolution to evaluate amorphous and pleomorphic breast tissue microcalcifications. CONCLUSION Synchrotron radiation imaging depicted microcalcifications as small as 24 microm. Imaging with this technique revealed that most amorphous and pleomorphic calcifications on conventional mammograms are clusters of fine specks and that in addition to the shape or density of a speck, the distribution density of clustered specks is a factor determining the apparent shape.

Feasibility Study of Weekly Nanoparticle Albumin-Bound Paclitaxel (150 mg/m2) Followed by Fluorouracil, Epirubicin, and Cyclophosphamide Therapy as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer

Background Although several studies have shown efficacy of nanoparticle albumin‐bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage and schedules were varied or used in combination and the data are still limited for weekly regimens. We evaluated the feasibility of weekly nab‐paclitaxel followed by FEC (5‐FU [fluorouracil], epirubicin, and cyclophosphamide) treatment feasibility as neoadjuvant chemotherapy for breast cancer. Patients and Methods Thirty‐three patients with no previous chemotherapy were enrolled to receive nab‐paclitaxel 150 mg/m2 the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant treatment. The trial was powered for analyses of feasibility. Results Twenty‐five patients completed the treatment as per protocol, and the completion rate was 75.8% (95% confidence interval, 59.0‐87.2; P = .44). The regimen completion group was younger than those with regimen incompletion (average 45.1 vs. 56.6 years). The pathological complete response (ypT0‐is/N0) rate was 30.3% in 33 patients, which was higher in triple‐negative patients (58.3%). Grade 3/4 neutropenia was seen in 48.5%, although there was no febrile neutropenia. Grade 3 peripheral neuropathy was seen in 33.3%. Conclusion Our study showed that weekly nab‐paclitaxel 150 mg/m2 3q4w followed by FEC as neoadjuvant regimen might be sufficient in efficacy, although with a relatively high severe adverse event occurrence rate. Micro‐Abstract In this single‐arm phase II study we evaluated the feasibility of weekly nanoparticle albumin‐bound paclitaxel 150 mg/m2 the first 3 of 4 weeks followed by FEC (5‐FU [fluorouracil], epirubicin, and cyclophosphamide) as neoadjuvant treatment for HER2‐negative breast cancer. The completion rate was 75.8% (25 of 33) and the pathological complete response rate was 30.3% (10 of 33). The efficacy might be sufficient, although relatively frequent Grade 3 neutropenia and peripheral neuropathy occurred.

Clinicopathological Significance of TARBP2, APP, and ZNF395 in Breast Cancer

The double-stranded RNA-binding protein TARBP2 has been suggested to act as an upstream regulator of breast cancer metastasis by destabilizing transcripts of the possible metastasis suppressors amyloid precursor protein (APP) and ZNF395. We examined this hypothesis by immunostaining of TARBP2, APP, and ZNF395 in 200 breast cancer specimens using tissue microarrays and analyzed the relationships between expression levels and clinicopathological parameters and prognosis. Increased TARBP2 overexpression was associated with shorter overall survival and disease-free survival, and increased but not reduced APP expression correlated with lower overall survival and disease-free survival. ZNF395 expression levels had no prognostic value, but reduced expression correlated with reduced lymph node metastasis. There was no significant relationship between TARBP2 overexpression and reduced APP and/or ZNF395 expression. Patients with tumors with higher TARBP2 or APP expression had unfavorable prognoses. Although reduced ZNF395 expression was significantly related to reduced lymph node metastasis, further studies are needed to clarify the role of TARBP2/APP/ZNF395 in breast cancer.

663 Histological correlations with the visibility of tumor extension in 3-D MR-mammography of breast cancer

Magnetic resonance imaging of the breast (MR-Mammography, MRM) is useful for surgical planning if it could show high tumor-gland contrast and clear three-dimensional (3-D) demonstration. In this study histological correlations with the visibility of tumor extension in 3-D MRM (0.5 T) were evaluated in 21 breast cancer cases. Tl weighted gradient echo with fat suppression and magnetization transfer contrast were obtained pre and postinfusion of Gd-DTPA. 3-D reconstruction was done for preoperative mapping of tumor extension. In 15 out of 21 cases (71%) tumor lesions could be clearly demonstrated against fatty breast gland. The fat suppression was effective to determine the invasion of tumor into the pectoral muscle. In 6 out of 21 cases (29%) the tumor lesions could not be clearly separated from the breast gland surround-ing them. In these cases either numerous loubles remained surrounding the tumor or marked intraductal spreading of cancer were observed. In conclusion, 3-D MRM is useful for surgical planning. However, the visibility of tumor mainly depends on the nature of background gland.