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.

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

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.