Kazuyoshi Motomura

The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase‐polymerase chain reaction

Background. The development of a sensitive method for the detection of breast carcinoma micrometastases in axillary lymph nodes is reported.

Fibroadenoma and Phyllodes Tumor

Background. The histogeneses of fibroadenoma and phyllodes tumor of the breast appear to be closely related, but it is still unclear whether fibroadenoma can progress directly to phyllodes tumor.

Combination technique is superior to dye alone in identification of the sentinel node in breast cancer patients.

The purpose of the present study was to evaluate whether the combination of dye and radioisotope would improve the detection rate of sentinel nodes (SN) and the diagnostic accuracy of axillary lymph node status over dye alone in patients with breast cancer.

Lymphoscintigraphic visualization of internal mammary nodes with subtumoral injection of radiocolloid in patients with breast cancer.

ObjectiveTo determine whether subtumoral injection of radiocolloid is useful for lymphoscintigraphic visualization of the internal mammary node and in sentinel lymph node (SLN) biopsy of the axilla in breast cancer patients. Summary Background DataThe presence of retromammary lymphatics connecting to the axillary and internal mammary basins has been demonstrated by early anatomic studies. Thus, it is hypothesized that some lymph, especially that from the parenchyma under the tumor, may drain into both the axillary and internal mammary basins. MethodsPatients (n = 196) with T1-2, N0 breast cancer underwent preoperative lymphoscintigraphy with radiocolloid (technetium 99m tin colloid) injection into various sites of the breast, followed by SLN biopsy using the combined method with blue dye. Patients were divided into four groups: group A (n = 41), peritumoral injection of both radiocolloid and blue dye; group B (n = 70), periareolar radiocolloid and peritumoral blue dye; group C (n = 45), intradermal radiocolloid and periareolar blue dye; and group D (n = 40), subtumoral radiocolloid and intradermal blue dye. A retrospective analysis of 1,297 breast cancer patients who underwent extended radical mastectomy with internal mammary node dissection was also conducted to determine the relationship between vertical tumor location (superficial or deep) and frequency of axillary and internal mammary node metastases. ResultsOne patient (2%) in group A, 3 (4%) in group B, 0 (0%) in group C, and 15 (38%) in group D exhibited hot spots in the internal mammary region on lymphoscintigraphy (P < .001, group D vs. the other groups). The concordance rate of radiocolloid and blue dye methods in detection of SLNs in the axillary basin was significantly lower in group D than in the other groups. In contrast, the mismatch rate (some SLNs were identified by radiocolloid and other SLNs were identified by blue dye, but no SLN was identified by both in the same patient) was significantly higher in group D than in the other groups. In patients treated with extended radical mastectomy, positivity of axillary and internal mammary metastases was significantly higher in patients (n = 215) with deep tumors than those (n = 368) with superficial tumors. ConclusionsThese results suggest the presence of a retromammary lymphatic pathway from the deep portion of the breast to both axillary and internal mammary basins, which is distinct from the superficial pathway. Therefore, SLN biopsy with a combination of subtumoral and other (peritumoral, dermal, or areolar) injections of radiocolloid will improve both axillary and internal mammary nodal staging.

Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers.

Collagen gel droplet embedded culture‐drug sensitivity test (CD‐DST) is the newly developed in vitro chemosensitivity test that has several advantages over the conventional ones. The aim of the present study is to examine the clinical usefulness of this test in the prediction of response to chemotherapy in breast cancer patients. Seventy patients with primary (n = 45) or locally recurrent (n = 25) breast cancers were recruited, and each patient underwent tumor biopsy before chemotherapy. The biopsy specimens were used for CD‐DST and immunohistological examination of 6 biological markers (P‐gp, erbB2, p53, BCL2, MIB1 and ER‐α). As chemotherapy, cyclophosphamide 600 mg/m2 plus epirubicin 60 mg/m2 q3w (CE, n = 28) or docetaxel 60 mg/m2 q3w (DOC, n = 42) was given. Interpretable results using the CD‐DST assay were obtained from 84.3% (59/70) of tumor specimens studied. Of the 18 tumors diagnosed as CE sensitive by CD‐DST, 15 (83.3%) exhibited a response to CE therapy and none of the 5 tumors diagnosed as CE resistant by CD‐DST exhibited a response to CE therapy. Of the 14 tumors diagnosed as DOC sensitive by CD‐DST, 13 (92.9%) exhibited a response to DOC therapy and only one of the 22 tumors diagnosed as DOC resistant by CD‐DST exhibited a response to DOC therapy. P‐gp expression was found to exhibit a significant (p < 0.05) association with the resistance to CE therapy but not to DOC therapy. Diagnostic accuracy (72.7%) achieved by P‐gp was lower than that (87.0%) achieved by CD‐DST in CE therapy. Expressions of other biological markers (erbB2, p53, BCL2, MIB1 and ER‐α) were not significantly associated with response to CE or DOC therapy. These results demonstrate that CD‐DST can predict the response to CE and DOC therapy with a high accuracy in breast cancer patients and seems to be superior to the conventional predictors.

Down-regulation of transforming growth factor-α by tamoxifen in human breast cancer

Background. The influence of tamoxifen treatment on transforming growth factor‐α (TGF‐α) levels in human breast cancer rarely has been studied in vivo.

Loss of alleles at loci on chromosome 13 in human primary gastric cancers.

Mitotic events leading to the loss of the normal allele corresponding to a mutated gene are important for tumorigenesis in rare heritable tumors such as retinoblastoma and Wilms tumor. As reported for both colorectal and breast cancers, some common tumors seem to develop because of the same mitotic events. We examined constitutional and tumor genotypes defined by polymorphic DNA clones in 36 patients with gastric cancer. In 14 cases, constitutional heterozygosity at loci on chromosome 13 had been lost. Loss of alleles was also detected at a locus on chromosome 18 in two cases and at a locus on chromosome 17 in one case. The frequent loss of alleles at loci on chromosome 13 (41%) suggests that elimination of genes on this chromosome may be of importance in the tumorigenesis of human primary gastric cancers.

Sentinel node biopsy in breast cancer patients with clinically negative lymph-nodes

BackgroundThe purpose of the present study is to evaluate the usefulness of dye-guided sentinel node biopsy in breast cancer patients with clinically negative nodes and to clarify the anatomic distribution of sentinel nodes in the axilla.MethodsSentinel node biopsy was performed in patients with T1 or T2 breast cancer who had clinically negative nodes, using an indocyanin green dye-guided method. Thereafter, complete axillary dissection was performed. Sentinel node and complete axillary lymph-node dissection specimens were examined separately, and the incidence of metastases was compared.ResultsWe identified sentinel nodes in 115 (76.7%) of 150 patients with clinically negative nodes. The mean number of sentinel nodes was 1.7 (range, one to eight nodes). The mean size of sentinel nodes was 9.0 mm (range, 2.0 to 28.0 mm). Of the 31 patients who had a tumor-positive sentinel node, 14 (45.2%) patients had only the sentinel node involved. There was concordance on histological examination between sentinel node and axillary node status in 111 (96.5%) of 115 cases. Of the sentinel nodes 89.1% were located cranially to the intercostobrachial nerve and within 2 cm of the lateral edge of the pectoralis minor muscle.ConclusionsSentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable detection rate of sentinel nodes for breast cancer patients with clinically negative nodes. Most of the sentinel nodes were located near the lateral edge of the pectoralis minor muscle and cranial to the intercostobrachial nerve.

Histologic characteristics of breast cancers with occult lymph node metastases detected by keratin 19 mRNA reverse transcriptase‐polymerase chain reaction

Amplification of keratin 19 mRNA (K19) by reverse transcriptase‐polymerase chain reaction (RT‐PCR) has been shown to be a sensitive method to detect occult breast cancer metastases in lymph nodes.

SPIO-Enhanced Magnetic Resonance Imaging for the Detection of Metastases in Sentinel Nodes Localized by Computed Tomography Lymphography in Patients with Breast Cancer

BackgroundSuperparamagnetic nanoparticle-enhanced magnetic resonance (MR) imaging has been reported to be a promising improvement for diagnostic imaging of lymph node metastases from various tumors. Moreover, sentinel nodes have been reported to be well identified using computed tomography (CT) lymphography (CT-LG) in patients with breast cancer. The aim of this study was to evaluate MR imaging with superparamagnetic iron oxide (SPIO) enhancement for the detection of metastases in sentinel nodes localized by CT-LG in patients with breast cancer.MethodsThis study included 102 patients with breast cancer and clinically negative nodes. Sentinel nodes were identified by CT-LG, and SPIO-enhanced MR imaging of the axilla was performed to detect metastases in the sentinel nodes. A node was considered nonmetastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show low signal intensity on MR imaging. Sentinel node biopsy was performed, and imaging results were correlated with histopathologic findings.ResultsThe mean number of sentinel nodes identified by CT-LG was 1.1 (range, 1–3). The sensitivity, specificity, and accuracy of MR imaging for the diagnosis of sentinel node metastases were 84.0%, 90.9%, and 89.2%, respectively. In 4 of 10 patients with micrometastases, metastases were not detected, but all 15 patients with macrometastases were successfully identified.ConclusionsSPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT-LG in patients with breast cancer and may avoid sentinel node biopsy when the sentinel node is diagnosed as disease-free.Superparamagnetic nanoparticle-enhanced magnetic resonance (MR) imaging has been reported to be a promising improvement for diagnostic imaging of lymph node metastases from various tumors. Moreover, sentinel nodes have been reported to be well identified using computed tomography (CT) lymphography (CT-LG) in patients with breast cancer. The aim of this study was to evaluate MR imaging with superparamagnetic iron oxide (SPIO) enhancement for the detection of metastases in sentinel nodes localized by CT-LG in patients with breast cancer. This study included 102 patients with breast cancer and clinically negative nodes. Sentinel nodes were identified by CT-LG, and SPIO-enhanced MR imaging of the axilla was performed to detect metastases in the sentinel nodes. A node was considered nonmetastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show low signal intensity on MR imaging. Sentinel node biopsy was performed, and imaging results were correlated with histopathologic findings. The mean number of sentinel nodes identified by CT-LG was 1.1 (range, 1–3). The sensitivity, specificity, and accuracy of MR imaging for the diagnosis of sentinel node metastases were 84.0%, 90.9%, and 89.2%, respectively. In 4 of 10 patients with micrometastases, metastases were not detected, but all 15 patients with macrometastases were successfully identified. SPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT-LG in patients with breast cancer and may avoid sentinel node biopsy when the sentinel node is diagnosed as disease-free.