Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study,we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection. Originally published Journal of Molecular Diagnostics, Vol. 7, No. 3, Aug 200

Prospective randomized study comparing cryo-assisted and needle-wire localization of ultrasound-visible breast tumors

Background This study compared the surgical results of 2 localization methods\u97cryo-assisted localization (CAL) and needle-wire localization (NWL)\u97in patients undergoing breast lumpectomy for breast cancer. Methods A total of 310 patients were treated in an institutional review board\u96approved study with 18 surgeons at 17 sites. Patients were randomized 2:1 to undergo either intraoperative CAL or NWL. A cryoprobe was inserted under ultrasound guidance in the operating room and an ice ball created an 8- to 10-mm margin around the lesion. The palpable ice ball then was dissected. NWL was placed according to institutional practice and resection was performed in a standard fashion. Surgical margins, complications, re-excisions, tissue volume, procedure times, ease of localization, specimen quality, and patient satisfaction were evaluated. Positive margins were defined as any type of disease present 1 mm or less from any specimen edge. Results Positive margin status did not differ between the 2 groups (28% vs. 31%). The volume of tissue removed was significantly less in the CAL group (49 vs. 66 mL, P =3D .002). Re-excisions were similar in both groups. CAL was superior in ease of lumpectomy, quality of specimen, acute surgical cosmesis, short-term cosmesis, patient satisfaction, and overall procedure time for the patient. CAL had a lower invasive positive margin rate (11% vs. 20%, P =3D .039) but a higher observed ductal carcinoma in situ\u96positive margin rate (30% vs. 18%, approaching statistical significance, P =3D .052). Conclusions CAL is a preferred alternative to standard wire localization because it provides a palpable template, removes less tissue and improves cosmesis, decreases overall procedure time, and is more convenient for the patient and surgeon

Prospective Study Comparing Surgeons' Pain and Fatigue Associated with Nipple-Sparing versus Skin-Sparing Mastectomy

Background. Nipple-sparing mastectomy (NSM) is more technically challenging than skin-sparing mastectomy (SSM) but offers quality-of-life and cosmetic advantages. However, surgeon physical symptoms related to NSM workload have not been documented. Methods.This was a prospective study using questionnaires to compare surgeon-reported physical symptoms before, during, and after NSM versus SSM. Surgeons also answered general questions about each mastectomy. Bilateral cases were performed simultaneously by two surgeons, who completed independent questionnaires. Result. Questionnaires were completed after 82 SSMs and 44 NSMs. On a 0-10 scale, surgeons reported NSM was more physically demanding than SSM (7.0 vs. 4.5, p < 0.001). Mean visualization was more difficult (5.7 vs. 3.2, p < 0.001) and mean fatigue score was greater (5.6 vs. 3.1, p < 0.001) after NSM than SSM. The mean increase in neck pain (on a 0-4 scale) was greater for NSM than SSM, both from before-to-during surgery (0.8 vs. 0.2, p = 0.003) and before-to-after surgery (0.9 vs. 0.2, p = 0.002). The mean increase in lower back pain was greater for NSM than SSM, both from before-to-during surgery (0.7 vs. 0.2, p = 0.008) and before-to-after surgery (0.9 vs. 0.2, p = 0.003). Surgeons reported that NSM was more mentally demanding (p < 0.001), complex (p = 0.01), and difficult (p < 0.001) than SSM. Conclusion. Surgeons experienced greater physical symptoms, mental strain, and fatigue with NSM than SSM. This raises concern that mild but repetitive pain over the course of a breast surgeon's career may lead to repetitive stress injury