EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial.

BACKGROUND: Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in the North Central Cancer Treatment Group (NCCTG) N9831 trial. METHODS: Tissue microarrays were constructed that allowed analysis of 1365 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA platform. The result was validated using an independent retrospective metastatic breast cancer cohort (n=130). RESULTS: Epidermal growth factor receptor assessed as a continuous (logarithmic transformed) variable shows an association with disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28-3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an HR associated with high EGFR expression of 1.92 (P=0.0073). CONCLUSIONS: High expression of EGFR appears to be associated with decreased benefit from adjuvant concurrent trastuzumab. Since other treatment options exist for HER2-driven tumours, further validation of these data may select patients for alternative or additive therapy.

The changing landscape of axillary surgery: which breast cancer patients may still benefit from complete axillary lymph node dissection?

BACKGROUND AND OBJECTIVES: Many breast cancer patients undergoing completion axillary lymph node dissection (CALND) for sentinel lymph node (SLN) metastases have no further disease. Predicting patients at high risk of non-sentinel lymph node (NSLN) metastasis may help guide effective utilization of CALND. METHODS: SLN+ breast cancer patients undergoing frozen section (FS) analysis at a single institution (2004-2010) were studied retrospectively. Factors associated with NSLN metastases were identified. RESULTS: Two-hundred forty SLN+ patients were identified. The incidence of NSLN metastases was 45% in FS(+) patients undergoing CALND, compared to 10% of FS(-) patients following CALND (P < 0.001). Multivariate analysis revealed that FS positivity, tumor size, and the presence of angiolymphatic invasion were significant factors associated with NSLN metastases (all P < 0.05). Further analysis of FS(+) patients revealed that tumor size, ER(-) status, and lymph node metastasis size were also associated with risk of NSLN metastases. An algorithm for the management of the axilla in SLN+ breast cancer patients was devised, based on clinic-pathologic predictors of NSLN metastases. CONCLUSION: A SLN+ biopsy by FS predicts the presence of NSLN metastases and, in combination with other factors, may justify immediate CALND. CALND may, however, be avoided in selected low-risk SLN+ patients.

Primary ovarian malignant lymphoma presenting as ovarian carcinomatosis: a case report and literature review.

INTRODUCTION: Primary ovarian lymphoma may present with a clinical scenario consistent with advanced epithelial ovarian carcinoma. Although ovarian lymphoma is a rare entity, accounting for 0.5% of all non-Hodgkin's lymphoma and 1.5% of all ovarian neoplasms, it should be included in the differential diagnosis of an ovarian mass. CASE: We report a case of a 78-year-old woman who presented with an ovarian neoplasm suggestive of advanced ovarian carcinoma. During diagnostic laparoscopy, biopsies were obtained with frozen section analysis revealing malignant lymphoma. Further histopathologic analysis revealed a diffuse large B-cell lymphoma (DLBCL). The treatment plan was for six cycles of R-CHOP chemotherapy. A drammatic response was noted after only three cycles of R-CHOP. CONCLUSION: Primary ovarian lymphoma presenting as an ovarian tumor is exceedingly rare. Since the prognosis and treatment of lymphoma differs significantly from ovarian carcinoma, a representative tissue sample of the adnexal tumor should be obtained and sent for frozen section analysis to establish the diagnosis. Principal treatment for non-Hodgkin's lymphoma is chemotherapy without surgical cytoreductive efforts.

Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.

BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention. METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging. RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging. CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.

Tracheopathia osteoplastica: familial occurrence.

Tracheopathia osteoplastica is an unusual disease characterized by cartilaginous or bony projections into the tracheobronchial lumen, with sparing of the posterior membranous portion of the tracheobronchial tree. The cause of this disorder is unknown. The diagnosis is seldom made because of the chronic and asymptomatic nature of the condition. More than 90% of the cases are diagnosed at postmortem examination. Symptoms may include dyspnea, coughing, hemoptysis, hoarseness, and wheezing. Tomography of the trachea may reveal beaded calcification of the tracheobronchial cartilages. Bronchoscopy is diagnostic. Histologically, the abnormal growths show heterotopic bone formation. No known treatment is available. We describe two female patients, one with hemoptysis and another with asthmalike symptoms, in both of whom bronchoscopy established the diagnosis of tracheopathia osteoplastica. The first patient had recurrent episodes of pneumonia attributable to bronchial obstruction by bony projections. In the second patient, removal of large lesions that obstructed the upper part of the trachea relieved the dyspnea. Of interest is the fact that the first patient was the biologic mother of the second. To our knowledge, this constitutes the first report of familial occurrence of tracheopathia osteoplastica.

Detection of Coccidioides species in clinical specimens by real-time PCR.

Coccidioides spp. are dimorphic fungal pathogens endemic to the semiarid regions of North, Central, and South America. Currently, direct smear and culture are the most common means of identifying Coccidioides spp. While these methods offer relatively sensitive and specific means of detecting Coccidioides spp., growth in culture may take up to 3 weeks, potentially delaying the diagnosis and initiation of appropriate antifungal therapy. In addition, growth of the organism represents a significant safety risk to laboratory personnel. The need for a rapid and safe means of diagnosing coccidioidomycosis prompted us to develop a real-time PCR assay to detect Coccidioides spp. directly from clinical specimens. Primers and fluorescent resonance energy transfer (FRET) probes were designed to target the internal transcribed spacer 2 region of Coccidioides. The assay's limit of detection is below 50 targets per reaction. An analysis of 40 Coccidioides sp. clinical isolates grown in culture demonstrated 100% sensitivity of the assay. A cross-reactivity panel containing fungi, bacteria, mycobacteria, and viruses was tested and demonstrated 100% specificity for Coccidioides spp. An analysis of 266 respiratory specimens by LightCycler PCR demonstrated 100% sensitivity and 98.4% specificity for Coccidioides spp. compared with culture. Analysis of 66 fresh tissue specimens yielded 92.9% sensitivity and 98.1% specificity versus those of the culture method. The sensitivity of the assay testing 148 paraffin-embedded tissue samples is 73.4%. A rapid method for the detection of Coccidioides spp. directly from clinical material will greatly assist in the timely diagnosis and treatment of patients, while at the same time decreasing the risk of accidental exposure to laboratory personnel.