Purpose: Detection of sentinel lymph node (SLN) metastasis in breast cancer patients has conventionally been determined by intraoperative histopathologic examination of frozen sections followed by definitive postoperative examination of permanent sections. The purpose of this study is to develop a more efficient method for intraoperative detection of lymph node metastasis. Experimental Design: Cutoff values to distinguish macrometastasis, micrometastasis, and nonmetastasis were determined by measuring cytokeratin 19 (CK19) mRNA in histopathologically positive and negative lymph nodes using one-step nucleic acid amplification (OSNA). In an intraoperative clinical study involving six facilities, 325 lymph nodes (101 patients), including 81 SLNs, were divided into four blocks. Alternate blocks were used for the OSNA assay with CK19 mRNA, and the remaining blocks were used for H&E and CK19 immunohistochemistryb ased three-level histopathologic examination. The results from the two methods were then compared. Results: We established CK19 mRNA cutoff values of 2.5 Â 10 2 and 5 Â 10 3 copies/AL. In the clinical study, an overall concordance rate between the OSNA assay and the three-level histopathology was 98.2 %. Similar results were obtained with 81 SLNs. The OSNA assay discriminated macrometastasis from micrometastasis. No false positive was observed in the OSNA assay of 144 histopathologically negative lymph nodes from pN0 patients, indicating an extremely low false positive for the OSNA assay. Conclusion: The OSNA assay of half of a lymph node provided results similar to those of three-level histopathology. Clinical results indicate that the OSNA assay provides a useful intraoperative detection method of lymph node metastasis in breast cancer patients.Sentinel lymph node (SLN) biopsy has recently become a standard surgical procedure in the treatment of breast cancer patients (1 -10). This procedure can predict metastasis to the regional lymph nodes with high accuracy and avoids unnecessary removal of axillary lymph nodes and subsequent morbidity associated with axially clearance in node negative breast cancer patients.SLN metastasis is generally detected by conventional means including the intraoperative H&E-based histopathologic examination of frozen section(s) or cytologic observation of touchimprints, followed by definitive postoperative histopathologic examination of permanent sections (2, 7 -9). However, the sensitivity of these intraoperative methods is not high. Many investigators have reported that the intraoperative H&E-based histopathologic examination has a false-negative rate of 5% to 52% (reviewed in ref. 11). Furthermore, these methods provide subjective rather than objective results, which may differ from one pathologist to another (12). On the other hand, the definitive postoperative histopathologic examination generally requires 5 to 10 days for assessment. If an accurate Imaging, Diagnosis, Prognosis

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Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation were clarified by means of a case‐control study of matched non‐pregnant and non‐lactating patients with breast cancer. From 18 institutions in Japan, a total of 192 subjects with breast cancer diagnosed during pregnancy (72 cases) and lactation (120 cases) were collected between 1970 and 1988, accounting for 0.76% of all breast cancer patients. The duration of symptoms was longer and tumor size was larger in the study subjects. Although the disease‐free interval was longer than that in the control patients, the survival time was shorter. There was no characteristic difference in histologic type. Vascular invasion and lymph node metastasis were found more frequently in the subjects. The positive rates of estrogen receptor and progesterone receptor were lower in the subjects. The 5‐ and 10‐year survival rates of the study patients were 65% and 55%, respectively, and these survivals were significantly lower than those of the control (P < 0.001). The survival rates were poorer in the subjects, in accordance with stage and lymph node metastasis. The results suggest that most of the patients with breast cancer diagnosed during pregnancy and lactation are in a more advanced stage because of a delay in detection and diagnosis, and hence have unfavorable prognosis. Therefore, it is important to diagnose and treat early for improvement of prognosis in patients with breast cancer during pregnancy and lactation.

Purpose: Accurate assessment of metastasis in sentinel lymph nodes (SLN) of breast cancer is important but involves a heavy workload for the pathologist.We conducted a multicenter clinical trial in Japan to evaluate a new automated assay system for cytokeratin 19 mRNA, the one-step nucleic acid amplification (OSNA) assay (Sysmex), to detect lymph node metastasis of breast cancer. Experimental Design: Surgically obtained axillary lymph nodes were sectioned into four pieces, two of which were examined with the OSNA assay. The other two adjacent pieces were examined with H&E and immunohistochemical staining for cytokeratin 19. Serial sections at 0.2-mm intervals were used in trial 1 to determine the specificity of the OSNA assay, and three pairs of sections cut from the sliced surfaces of the pieces were used in trial 2 to compare the accuracy of the OSNA assay with that of a routine pathologic examination for SLNs in Japan. Results: In trial 1, the sensitivity and specificity were 95.0% [95% confidence interval (95% CI), 75.1-99.9 %] and 97.1% (95 % CI, 91.8-99.4%), respectively, for 124 axillary lymph nodes obtained from 34 patients. In trial 2, the agreement between findings of the assay and of the pathologic examination was 92.9% (95% CI, 90.1-95.1%) for 450 axillary lymph nodes obtained from 164 patients. Conclusion: The OSNA assay can detect lymph node metastasis as accurately as can conventional pathology and thus can be an effective addition to or alternative for rapid intraoperative examination of SLNs.Sentinel lymph node (SLN) biopsy for breast cancer is expected to become a standard surgical procedure in the near future, and accurate assessment of metastasis of SLNs is essential for making decisions about the avoidance of unnecessary axillary dissection and the provision of appropriate adjuvant treatment for patients. However, methods for the pathologic examination of SLNs to detect metastasis remain controversial (1 -4). Although more detailed examination of SLNs can provide more accurate information about metastasis (5), to obtain more accurate results, a comparatively greater number of pathologic specimens need to be examined (6). This involves much time for preparation of the specimens and a heavy workload for pathologists to examine them, especially intraoperatively.To overcome these problems, molecular detection of metastasis has been developed as one of the most promising methods for SLN examination. With this procedure, the whole lymph node can be examined during a short time

Background. The development of a sensitive method for the detection of breast carcinoma micrometastases in axillary lymph nodes is reported. Methods. The method was based on amplification of MUCl mRNA, which encodes a core protein of polymorphic epithelial mucin, by a reverse transcriptase‐polymerase chain reaction (RT‐PCR). Total RNA, which was extracted from a breast carcinoma cell line (MCF‐7), primary breast carcinomas, and axillary lymph nodes, was subjected to analysis of MUCl mRNA expression by the RT‐PCR method. Results. MUCl mRNA expression was detected by RT‐PCR in MCF‐7 cells and in all 15 primary breast carcinomas but not in control lymph nodes taken from patients with benign diseases. A serial dilution study revealed that MUCl RT‐PCR was a very sensitive method, detecting one MCF‐7 cell per 1,000,000 lymph node cells. The detection sensitivity of MUCl RT‐PCR method was compared with that of immunohistochemical staining of an epithelial marker (polymorphic epithelial mucin). Fifty axillary lymph nodes were obtained from 15 patients with primary breast carcinomas, and metastasis in each lymph node was investigated by both methods. The immunohistochemical method demonstrated metastasis in nine lymph nodes, and MUCl mRNA was detected in all of them. Of the 41 lymph nodes that were diagnosed to be devoid of metastasis by immunohistochemistry, MUCl mRNA was expressed by 6 but not by the other 35, indicating the presence of micrometastases in these 6 lymph nodes that could be detected only by the MUCl RT‐PCR method. Conclusions. The MUCl RT‐PCR method is more sensitive than immunohistochemistry for the detection of micrometastases in axillary lymph nodes. This new method would be of practical value in selecting the patients at high risk for relapse from those who are histologically lymph node negative.

Intraoperative imprint cytology is a useful method for evaluating the status of sentinel nodes and is more accurate than frozen-section analysis. In addition, imprint cytology can detect micrometastasis more accurately than conventional haematoxylin and eosin-stained sectioning.

BACKGROUNDThe clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long‐term follow‐up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group.METHODSPatients (N = 1901)with unilateral breast cancer ≤ 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan–Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR.RESULTSAt a median follow‐up time of 107 months, the 10‐year overall and disease‐free survival rates were 83.9% and 77.8%, respectively. The 10‐year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10‐year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676–5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis.CONCLUSIONSYoung age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases. Cancer 2006. © 2005 American Cancer Society.

Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable success rate in detecting sentinel nodes and predicting axillary nodal status. Axillary node status, the presence or absence of lymphatic or vascular invasion in the tumor and patient age affect its success in identifying sentinel nodes.