Intraoperative assessment of sentinel lymph nodes after neoadjuvant chemotherapy in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). This study was designed to evaluate the ability of intraoperative assessment to predict metastasis in the sentinel node after NAC and to compare it with patients not treated with NAC. METHODS: Thirty-seven patients with invasive breast cancer and SLN biopsy after NAC and 461 patients with invasive breast cancer not treated with NAC were included in the study. The SLN was identified by the gamma probe and sent to pathology for frozen (FS) and H&E paraffin-sections. If the SLN was negative by H&E paraffin-sections, then immunohistochemistry was performed. RESULTS: The sensitivity of FS in the NAC group ranged from 78.5% for micro and isolated tumor cells to 100% for macrometastasis. The sensitivity of FS in the non-NAC group ranged from 82% for micro and isolated tumor cells to 97.4% for macrometastasis. There were no statistically differences between the sensitivities of FS in the two groups. Nine (64.2%) of the 14 patients in the NAC group with metastasis to the SLN had other non-SLN metastasis. CONCLUSIONS: After NAC, FS is an effective method for detecting macrometastasis in the SLN. As in the adjuvant setting, the sensitivity of FS is lower for SLN micro and sub-micrometastasis. Intraoperative FS of the SLN after NAC is indicated to avoid a second surgery because 60% of patients with a positive SLN will have additional positive axillary nodes.

Complete pathological remission in a patient with hormone-receptor positive and c-erbB-2 expression-negative breast cancer treated with FAC chemotherapy during pregnancy.

We describe the case of a pregnant woman diagnosed with breast cancer at 26 weeks' gestation. The tumor was positive for estrogen and progesterone receptors and negative for overexpression of c-erbB-2 protein. Neoadjuvant FAC (fluorouracil, adriamycin, cytoxan) chemotherapy was started at 29 weeks' gestation. At 37 weeks, delivery was induced and the patient gave born to a healthy female baby weighing 2350 g, after which she was given a further cycle of chemotherapy and weekly paclitaxel. Clinical and radiological remission was achieved. Resection of the breast tissue showed complete pathological response and negative lymph nodes. This case illustrates how the integrated work of different specialists can obtain excellent oncological and obstetrical results in the care of pregnant women with breast cancer.

4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis.

PURPOSE: Cell signaling pathways include a complex myriad of interconnected factors from the membrane to the nucleus, such as erbB family receptors and the phosphoinositide-3-kinase/Akt/mTOR and Ras-Raf-ERK cascades, which drive proliferative signals, promote survival, and regulate protein synthesis. EXPERIMENTAL DESIGN: To find pivotal factors in these pathways, which provide prognostic information in malignancies, we studied 103 human breast tumors with an immunohistochemical profile, including total and phosphorylated (p) proteins: human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, Akt, 4E-binding protein 1 (4EBP1), eukaryotic initiation factor 4E, phosphorylated ribosomal protein S6 kinase 1, phosphorylated ribosomal protein S6, and Ki67. Western blot and reverse lysate protein arrays were also done in a subset of tumors. RESULTS: Significantly, activation of the phosphoinositide-3-kinase/Akt/mTOR cascade was detected in a high proportion of tumors (41.9%). Tumors with HER2 overexpression showed higher p-Akt as compared with negative tumors (P < 0.001). Levels of p-Akt correlated with the downstream molecules, p-4EBP1 (P = 0.001) and p-p70S6K (P = 0.05). Although 81.5% of tumors expressed p-4EBP1, in 16.3% of these tumors, concomitant activation of the upstream factors was not detected. Interestingly, p-4EBP1 was mainly expressed in poorly differentiated tumors (P < 0.001) and correlated with tumor size (P < 0.001), presence of lymph node metastasis (P = 0.002), and locoregional recurrences (P = 0.002). Coexpression of p-4EBP1 and p-eIF4G correlated with a high tumor proliferation rate (P = 0.012). CONCLUSION: In this study, p-4EBP1 was the main factor in signaling pathways that associate with prognosis and grade of malignancy in breast tumors. Moreover, p-4EBP1 was detected in both HER2-positive and HER2-negative tumors. This factor seems to be a channeling point at which different upstream oncogenic alterations converge and transmit their proliferative signal, modulating protein translation.

The alpha angle as a predictor of contralateral slipped capital femoral epiphysis.

PURPOSE: Contralateral hip involvement in slipped capital femoral epiphysis (SCFE) is common. Femoral head-neck asphericity, as measured by an elevated alpha angle, has not previously been assessed with respect to SCFE risk. Our aim was to assess the utility of the alpha angle in predicting contralateral SCFE. METHODS: We retrospectively reviewed 168 patients (94 males) managed surgically for unilateral SCFE between 2001 and 2013 who had a minimum of 18 months follow-up. The alpha angle, the posterior sloping angle (PSA), and the modified Oxford score were recorded for every patient at the time of initial SCFE presentation. Follow-up clinical records and radiographs were assessed to determine the presence of absence of contralateral SCFE. RESULTS: Forty-five patients (27 %) developed a contralateral SCFE. Patients who developed a contralateral SCFE had a significantly higher alpha angle (51° vs 45°, p < 0.001) than patients who did not develop a contralateral SCFE. There was no significant difference in PSA or modified Oxford score (both p > 0.10) between patients who developed a contralateral SCFE and those who did not. Using a proposed alpha angle of 50.5° as a threshold for prophylactic fixation, 26 (58 %) of the 45 cases of contralateral SCFE in our study would have been prevented and 18 (15 %) of 123 patients would have undergone fixation unnecessarily. CONCLUSIONS: We found the alpha angle to positively correlate with contralateral SCFE risk. Patients with significantly elevated alpha angles may be at greater risk of contralateral SCFE and benefit from further investigation or prophylactic hip fixation.

Cyclo-oxygenase type 2 is dysregulated in breast ductal carcinoma in situ and correlates with poor outcome.

OBJECTIVE: Clinico-pathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 2003 TNM criteria (T1mic