Pathological aspects of the intraductal spread of breast cancer.

The intraductal spread of breast cancer is a major cause of local recurrence following breast-conserving therapy. To properly understand this pathology, three-dimensional (3D) cancer localization within the mammary ductal-lobular system (MDLS) is necessary. To this end we generated computer-assisted 3D reconstructions of all MDLSs using 2-mm-thick serial sections of surgically resected specimens. We then analyzed the characteristics of intraductal spread of breast cancer. In our study of quadrantectomy specimens from patients with primary invasive breast carcinoma, the intraductal spread of breast cancer was found to be continuous from the invasive tumor and spreading along the mammary glandular tree. The pattern is categorized into three types: the central type, the peripheral type, and the extensive type. The central type was found to be most common. A 3D analysis of total mastectomy specimen from a patient with primary non-invasive breast carcinoma revealed regional intraductal spread extending within and filling a single MDLS. The analysis also revealed the presence of ductal anastomoses connecting adjacent MDLSs. These ductal anastomoses were found to be an anatomical risk factor for extensive intraductal spread of breast cancer across multiple MDLSs. To minimize residual non-invasive components of breast carcinoma in the conserved breast, which is strongly associated with the outcome of local control of breast-conserving therapy, it is necessary to determine the optimum surgical margins in a flexible, patient-specific manner. This determination should be based on anatomical characteristics of the MDLS, such as those identified in the present study.

[Efficacy and safety of high-dose toremifene for hormone-responsive advanced or metastatic breast cancer patients with failed prior treatment by aromatase inhibitors].

BACKGROUND: Recently, aromatase inhibitors (AI) are widely used in postoperative adjuvant therapy for breast cancer. Nevertheless, studies of postoperative therapeutic strategies for recurrent breast cancer are insufficient. SUBJECTS AND METHOD: Data on 12 post-menopausal advanced/recurrent breast cancer patients in our department during June 2003- April 2007 were used for this study. No patient had responded to high-dose toremifene (TOR), a third-generation AI. Their therapeutic outcomes were analyzed retrospectively. The median observation period of the subjects was 16.1 months (4.0-40.9 months). Subjects were all hormone-sensitive. Overexpression of HER2 protein was found in only one case. During AI therapy immediately prior, exemestane (EXE) and anastrozole (ANA) had been given in nine and three cases, respectively. RESULTS: The complete response rate of AI therapy was 16.7% (2/12). The clinical benefit rate was 58.3% (7/12). The median of time to progression (TTP) was 33.8 weeks. Neither the presence nor absence of past history of treatment with tamoxifen (TAM) or other chemotherapies affected the anti-tumor effect. Analysis by the site of metastasis or recurrence revealed that the therapeutic effects were better for non-life-threatening cases in the lung, pleura, soft tissue, etc. The severities of adverse effects were all less than grade 2; the major ones were flushing and sweating. CONCLUSION: Results show that high-dose TOR given at an early stage can provide clinical benefits for post-menopausal advanced/recurrent breast cancer not responding to AI.

[Combination treatment with trastuzumab and Paclitaxel as primary therapy for advanced breast cancer].

PURPOSES: Despite many recent reports on the effects of trastuzumab for breast cancer, many problems remain regarding combination drug treatment and its significance. We report our experience with advanced breast cancer patients who received combination therapy with trastuzumab+paclitaxel. SUBJECTS AND METHOD: Three patients with human epidermal growth factor receptor 2(HER2)-positive advanced breast cancer were the subjects. Combination therapy with trastuzumab and paclitaxel was carried out as a primary therapy, and its therapeutic effects were evaluated based on image findings, tumor markers and observation of resected specimens. RESULTS: The primary tumors in the three patients were all clinically complete response (cCR). Those in two surgically treated patients were near pathologically complete response (pCR), ie, a small amount of cancer cells remained in the galactophore, whereas the histological therapeutic effect was Grade 2b. In two patients with liver metastases, the metastatic tumor disappeared on the image after the therapy. In two patients whose tumor marker was increased at the first examination, the level of increase was markedly lowered by the therapy. Neither infusion reaction nor heart functional impairment was found in any of the three patients. CONCLUSIONS: For patients with advanced breast cancer, a regimen containing trastuzumab would produce significant therapeutic effects if the cancer is HER2-positive. The regimen would also contribute to the prognosis of such patients since it might produce pCR. Since the risk of severe adverse effects is low and the treatment with trastuzumab can be conducted safely as an ambulatory treatment, high patient QOL seems possible. These findings suggest that combination therapy with trastuzumab+paclitaxel is effective as a primary therapy for HER2-positive advanced breast cancer.

Anthraquinone derivatives as a new family of protein photocleavers.

Certain anthraquinones, which are present in many biologically important natural products, effectively and randomly cleaved proteins (BSA or Lyso) during photoirradiation using a long wavelength UV light without any further additives. It was also found that this ability could be improved by the attachment of a suitable substituent into the anthraquinone core skeleton.

Histological distribution and ultrastructural features of immunoreactive terminals against RT97, a monoclonal antibody to a 200 kD neurofilament, in the spinal dorsal horn of a rat.

Localization and ultrastructural features of immunoreactive fibers and terminals against RT-97, a mouse monoclonal antibody that recognizes subunit of a 200-kD neurofilament, were examined in the spinal dorsal horn of adult rats. Under a light-microscope, many RT-97 immunoreactive fibers were detected in the dorsal root, collaterals of the dorsal root in the dorsal funiculus, and laminae III and IV in the dorsal horn. Few immunoreactive fibers were found in laminae I and II. Electron microscopic observation demonstrated that almost all RT-97 immunoreactive fibers in the dorsal root were myelinated, and unmyelinated fibers immunonegative. The immunoreactive fibers entered into the dorsal horn passing through the collaterals of the dorsal root along the superficial gray lamina. In the dorsal horn, these fibers ascended into and then terminated in lamina II. RT-97 immunoreactive central terminals were semicircular or ellipsoid in appearance and contained many flat-type presynaptic vesicles. Some terminals made synaptic contact with dendritic profiles in lamina II. Our present results indicate that RT-97 is a useful marker for ultrastructural examination of terminals served by non-nociceptive A-fibers.