Munehisa Yamato

Identification of high-risk breast cancer patients from genetic changes of their tumors.

To identify the genetic prognostic markers for breast cancer, we analyzed loss of heterozygosity (LOH) at 11p, 16q, 17p, 17q, and 18q, as well as amplification of theERBB2, INT2, andMYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of theERBB2, MYC, andINT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q andINT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q andINT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.

Touch imprint cytology with cytokeratin immunostaining versus Papanicolau staining for intraoperative evaluation of sentinel lymph node metastasis in clinically node-negative breast cancer

AIM This study investigated whether intraoperative assessment of SLN status in patients with clinically node-negative breast cancer was improved using touch imprint immunohistochemistry. MATERIAL AND METHODS Each SLN was cut into slices 2mm thick and evaluated intraoperatively by touch imprint cytology with Papanicolaou staining until the end of 2005, or by a combination of Papanicolaou staining and immunostaining with an anti-cytokeratin antibody from early 2006. RESULTS When intraoperative cytology of SLN in 85 patients who were clinically node-negative was evaluated with Papanicolaou staining, 81 patients were diagnosed as negative and four were positive. Intraoperative cytology with Papanicolaou staining had a sensitivity of 30%, specificity of 99%, false-negative rate of 70%, false-positive rate of 1.3%, and accuracy of 90.6%. When intraoperative cytology was done with immunohistochemistry plus Papanicolaou staining for SLN evaluation, 92 patients were diagnosed as negative and 17 patients were positive. Intraoperative cytology with immunohistochemistry had a sensitivity of 79%, specificity of 98%, false-negative rate of 21%, false-positive rate of 2.2%, and accuracy of 94.5%. Compared with intraoperative cytology using Papanicolaou staining alone, the combination of immunohistochemistry and Papanicolaou staining achieved a significant increase in sensitivity and a significant decrease in the false-negative rate. CONCLUSION Intraoperative SLN evaluation by imprint cytology with immunohistochemistry achieves a more accurate diagnosis of metastasis than imprint cytology alone. This combined method is considered useful for deciding whether to perform axillary lymph node dissection.

Hematoma-Directed and Ultrasound-Guided Breast-Conserving Surgery for Nonpalpable Breast Cancer After Mammotome Biopsy

Stereotactic vacuum-assisted (Mammotome™) breast biopsy is a powerful diagnostic tool for detecting microcalcifications on mammography, but it is difficult to remove the targeted lesion precisely when subsequent breast-conserving surgery is to be carried out. We achieved satisfactory results by performing hematoma-directed breast-conserving surgery after stereotactic Mammotome biopsy in seven patients. To identify the exact location of the Mammotome biopsy during the breast-conserving surgery, we created an iatrogenic hematoma in the biopsy cavity using patient’s blood. This hematoma was detected easily on intraoperative ultrasonography in all patients, and was palpable as a soft mass in five of the seven patients. The microcalcifications were completely removed in all patients, and no cancer cells were found in the margin surfaces after breast-conserving surgery. There were no complications during the injection of the patient’s blood into the biopsy cavity or during the hematoma-directed surgery. We describe this new procedure of hematoma-directed breast-conserving surgery following Mammotome biopsy for nonpalpable cancer with microcalcifications.

Clinical Experience of Weekly Paclitaxel-Based Treatment as Preoperative Chemotherapy for Patients with Primary Breast Cancer

BackgroundPaclitaxel is an effective agent in the treatment of metastatic breast cancer. The aim of this study was to evaluate the safety and efficacy of weekly paclitaxel-based preoperative chemotherapy in patients with large operable breast cancer.MethodsPatients initially received paclitaxel as a 3-hour infusion at 175 mg/m2. Three weeks after initial administration, two cycles of three weeks of paclitaxel 80 mg/m2 over a 1 hour infusion followed by a one week break were given. Of 22 patients, 9 had stage II (tumor diameter greater than 3 cm), 4 stage IIIA, 7 stage IIIB, and 2 stage IV (with ipsilateral supraclavicular lymph node metastasis) cancer, respectively.ResultsExcluding stageN patients, the overall response rate to paclitaxel chemotherapy was 80%. Four of the 20 patients (20%) showed a clinical complete response (cCR). Two of these showed pathologic complete response and the other 2 had only the ductal component remaining. The primary tumor response and axillary lymph node downstaging following preoperative chemotherapy tended to be related in 16 patients with clinically positive nodes. Breast conserving surgery was performed as a result of down-staging in the 9 stage II patients. Grade 3 neutropenia occurred in one patient when 175 mg/m2 of paclitaxel was administered, but no serious side effects developed during the weekly administration of paclitaxel.ConclusionThe use of weekly paclitaxel-based preoperative chemotherapy appears to yield a significant anti-tumor effect without inducing serious drug-related adverse effects. Furthermore, the effectiveness of this treatment appears to result in a higher frequency of breast conserving surgery.

The follow up study of intra-arterial infusion chemotherapy with local vein blocking as a surgical neo-adjuvant treatment for locally advanced breast cancer.

Preoperative intra-arterial infusion neo-adjuvant chemotherapy, in combination with local vein blocking, was administered to thirtyone patients with locally advanced stage III breast cancer. The anti-cancer drugs and dosages used were 500 mg of 5-Fluorouracil (5FU), which was infused daily for 7–14 days, and 20 mg of Adriamycin (ADM), which was administered as a bolus dose twice into the subclavian and internal mammary arteries. The response rate of this method on the primary tumor was 48.4 per cent, and, histologically it was found to be as high as 90.3 per cent. The response rate of the clinical effects on the regional lymph nodes was 50.0 per cent, however, histologically, it was found to be lower than that of the primary tumor. In the long-term follow up study the 5-year survival rate was 72.2 per cent. Thus, this method seems to be effective as a combined modality in cases of locally advanced stage III breast cancer.

Cytohistochemical studies on estrogen receptors of breast cancer tissue using an immunoperoxidase technique

The estrogen receptors (ER) in breast cancer tissues were investigated in 122 patients using an immunoperoxidase method. ER (+) were evident in 77 of 122 patients (63.1 per cent). If classified according to pre-and postmenopausal subjects. ER (+) was seen in 61.4 per cent and ER (−) in 32.9 per cent before menopause, and ER (+) in 65.4 per cent and ER (−) in 30.8 per cent after menopause with no marked difference between the two. If classified according to histological type, ER (+) was seen in 73.2 per cent of those with papillotubular carcinoma and in 62.0 per cent of those with scirrhous carcinoma, whereas ER (−) was seen in 44.9 per cent of those with medullary tubular carcinoma. ER (+) was seen in carcinoma with apocrine metaplasia, lobular carcinoma and Pagets carcinoma. Concerning the relationship between primary tumors and metastatic lymph nodes, ER (+) for both was seen in 20 of 41 patients (48.8 per cent) whereas ER (−) for both was found in 9 of 41 patients (22.0 per cent). Four patients with local recurrences had a positive ER (+) at the beginning of treatment, but the ER became negative after hormonal treatment and chemotherapy.