Abstract Big endothelin-1 (big ET-1) is the biological precursor of endothelin-1 (ET-1) and it is known as an indicator for the degree of activation of endothelin system. Therefore, this study was designed to investigate the serum big ET-1 levels in newly diagnosed primary breast cancer patients; before surgery and after adjuvant therapy. In addition this study was also aimed at examining the correlation between big ET-1 and CA15.3, clinical and pathological criteria of breast cancer, as well as their status during the follow up period after adjuvant therapy. The study consisted of 40 females with newly diagnosed primary breast cancer treated at the Medical Research Institute hospital and 15 healthy females as a control group. Before surgery, big ET-1 serum levels of all breast cancer patients were significantly higher than those of the control group (p<0.001). However, after both surgery and adjuvant therapy, big ET-1 was significantly decreased compared to its level before surgery (p<0.001). On the other hand, there was lack of significant differences in the levels of CA15.3, neither before surgery nor after the adjuvant therapy in comparison to the control group. Interestingly, during the follow up period, nine patients developed metastasis to different organs and their serum big ET-1 and CA15.3 levels significantly increased compared to the levels before surgery and after the adjuvant therapy (p<0.001, 0.008 and <0.001, 0.008 respectively). Inspite of this observation with this specific group of patients, the use of these markers to predict the development of metastasis during the follow up period cannot be generalized. Furthermore, both of these biochemical parameters showed no correlation to any of the clinicopathological parameters and patients characteristics. Therefore, in conclusion this study found that the testing for serum big ET-1 is more useful than CA15.3 for the diagnosis of breast cancer and future trials will be necessary to establish the importance of big ET-1 as a prognostic marker and to formulate a time-line for its measurement in patients with high risk for developing metastasis.
Keywords: breast cancer; big endothelin-1; CA 15.3; metastasis

Abstract Primary neuroendocrine carcinomas of the breast are extremely rare. Neuroendocrine tumors mainly occur in the broncopolmonary system and gastrointestinal tract. The diagnosis of small cell neuroendocrine carcinoma (SCNC) of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. We are going to describe two cases and to discuss their clinical, radiological and pathological manifestations. Introduction: Neuroendocrine tumors are rare and slow-growing neoplasias derived from neuroendocrine cells. We describe two cases of small cell neuroendocrine carcinoma of the breast and discuss their clinical, radiological and pathological manifestations. Case report: Our patients are two Italian females (38 and 36 year-old) with no family history of breast disease. In both cases the diagnosis was confirmed after surgery, when immunohistochemistry revealed a neuroendocrine differentiation of the tumor. The patients are alive and disease free after more than ten years of follow-up. Conclusion: Primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. After surgery, a strict follow-up including octreotide scan should be performed and this doesn’t differ from the one of the usual breast carcinoma.
Keywords: small cell neuroendocrine carcinoma; breast disease; scintigraphy; neuron-specific enolase (NSE); mammography