Bilateral De Quervain Syndrome after Aromatase Inhibitor Administration: A Case Report and Review of the Literature

Aromatase inhibitors are widely used as one of the main treatment options of both early and advanced hormone receptor-positive breast cancer in postmenopausal women. Unfortunately, musculoskeletal symptoms are often presented in patients treated with aromatase inhibitors (AIs), and, although the pathogenesis is unknown, postulated mechanisms have been described. Herein, to our knowledge, we present the first report of bilateral De Quervain syndrome related with AIs therapy with a review of the relevant literature

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

BACKGROUND: Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma. METHODS: We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters. RESULTS: HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. CONCLUSION: HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential

Study of EGFR (EGFR ή HER-1, HER-2, HER-3, HER-4) expression in colorectal adenocarcinomas: progostic significance and correlation with pathological variables

Background: In this study we sought to determine the pattern and the prognostic significance of EGFR, HER/2neu, HER-3 and HER-4 protein expression in colorectal adenocarcinoma. Methods: Immunohistochemistry was performed in paraffin embedded specimens of 106 colorectal carcinomas for the assessment of EGFR, HER-2, HER-3 and HER-4 protein expression. The results were correlated with traditional clinicopathological parameters and patient outcome. Results: Membranous expression of EGFR was found in 50 cases (47,16%) and cytoplasmic expression in 32 cases (30,18%). Membranous overexpression of Her2 was identified in 6 cases (5,66%) while cytoplasmic expression was found in 18 cases (16,98%). HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. The correlation with other clinicopathological parameters demonstrated a statistically significant expression of membranous EGFR in the older age group (p=0,009) and a statistically significant expression of membranous Her-2 in patients with negative lymph nodes (p=0,014). None of the other parameters or patient prognosis was associated with EGFR or HER-2 membranous expression. Cytoplasmic expression was not related with any of above studied parameters. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p=0,032) and older median age (p=0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymph nodes (p=0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. Conclusion: Conventional IHC was unable to reveal any association between EGFR expression and outcome predicted by the biological role of EGFR in tumor behavior. Her-2/neu is not a pivotal pathway in colorectal cancer progression as it seems to be expressed at early stages of colorectal cancer. HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential.Στόχος. Η μελέτη της έκφρασης και η προγνωστική αξία των υποδοχέων της οικογένειας του επιδερμικού αυξητικού παράγοντα στο καρκίνο του παχέος εντέρου. Μεθοδολογία. Μέσω ανοσοϊστοχημείας μελετήθηκε η έκφραση των υποδοχέων σε 106 βιοψίες ασθενών και τα αποτελέσματα συσχετίσθηκαν με την επιβίωση και κλινικοπαθολογικές παραμέτρους. Αποτελέσματα. Η μεμβρανική έκφραση του EGFR συσχετίσθηκε με ασθενείς μεγαλύτερης ηλικίας (p=0,009), ενώ η μεμβρανική έκφραση του HER-2 συσχετίσθηκε με ασθενείς στους οποίους δεν παρατηρείται διήθηση λεμφαδένων. Η κυτταροπλασματική έκφραση του HER-3 συσχετίσθηκε με ασθενείς μεγαλύτερης ηλικίας (p=0,010) και μέτριας διαφοροποίησης όγκους (p=0,032). Η μεμβρανική έκφραση του HER-4 συσχετίσθηκε με την παρουσία διηθημένων λεμφαδένων (p=0,0003), ενώ ασθενείς οι οποίοι δεν παρουσιάζουν μεμβρανική έκφραση συνδέονται με το στάδιο Β κατά Dukes’ (p=0,010). Δεν αναδείχθηκε συσχέτιση της έκφρασης των υποδοχέων με την επιβίωση. Συμπεράσματα. Η ανίχνευση του EGFR μέσω της μεθόδου της ανοσοϊστοχημείας δεν έχει προγνωστικό ρόλο όσον αφορά τη συμπεριφορά του καρκίνου του παχέος εντέρου. Η οδός του HER-2, η έκφραση του οποίου παρατηρείται στα αρχικά στάδια δεν είναι σημαντική. Η μεμβρανική έκφραση του HER-4 συνδέεται με προχωρημένη νόσο και αυτό πιθανώς αναδεικνύει όγκους με επιθετικότερη συμπεριφορά

Targeting the HER2 Receptor in Metastatic Breast Cancer

The advent of targeted therapies has revolutionized the treatment of certain types of cancer. Identification of molecular targets on cancer cells has led to the design of novel drugs, which either used as single agents or in combination with chemotherapy, has prolonged survival in metastatic disease, or contributed to curative treatment in the adjuvant setting. A literature review was conducted to identify and present current knowledge on the molecular function of the HER2 receptor, its role in the pathogenesis of breast cancer and anti-HER2 targeted drugs in use or under development. Many molecular targets have been identified in breast cancer, with the HER family of receptors being the ones most extensively studied. Trastuzumab and lapatinib target the HER2 receptor and are approved drugs for the treatment of metastatic breast cancer. Several other targeted agents, including T-DM1, pertuzumab, neratinib, afatinib and ertumaxomab, are currently being tested in vivo as well as in clinical studies. The use of targeted therapies in metastatic breast cancer has improved prognosis, increased survival and dramatically changed the way we treat breast cancer patients today