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Purpose: This study aimed to evaluate whether the Fischer score criteria on contrast-enhanced magnetic resonance (CE-MR) imaging could correlate with histopathological prognostic factors in invasive breast cancer., Materials and Methods: Seventy-two women with histologically proven invasive breast cancer underwent preoperative CE-MR imaging. Images were assessed for the following parameters, according to the scoring system described by Fischer in 1999: tumour shape, margins, internal enhancement, signal intensity increase, signal intensity course and overall Fischer score. Evaluated histopathological prognostic factors included histological type, associated extensive intraductal component, diameter, lymph node metastasis, tumour grade, and oestrogen receptor (ER), progesterone receptor (PgR), Ki67 proliferation, oncogene c-erbB-2 (HER2/neu) expression. Fisher's exact test was used to correlate the CE-MR imaging parameters and histopathological findings (with significance set a p < 0.05)., Results: Fischer's score was 0-4 in 14/72 (19%) cases, >4 in 58/72 (81%) and 3 in 5/72 (7%; false negative), with a sensitivity of 93%. A significant correlation (p=0.02) was found between stellate-dendritic shape and the presence of an associated extensive intraductal component (EIC), which was found in 78% of stellate tumours vs. 49% of round-oval tumours. A significant correlation (p=0.039) was found between Ki67 expression and signal intensity course (Ki67 overexpression was present in 81% of tumours with washout course vs. 21% with plateau course)., Conclusions: The CE-MR imaging findings that correlate with prognostic factors are shape and signal intensity curve. Fischer's multifactorial analysis was helpful in the interpretation of CE-MR images, showing a sensitivity of 93% for invasive breast cancer.

The neuroendocrine carcinoma of the breast is a very rare tumor. In this paper we describe our experience in 10 cases of neuroendocrine carcinoma of the breast, and an integrated diagnostic-therapeutic proposal for this tumor. Since no positive association has been shown between neuroendocrine differentiation and tumor size, staging, grading, survival and therefore prognosis, we consider that surgical therapy for neuroendocrine tumors of the breast should be the same as that performed in common invasive histotypes. Due to the presence of specific cellular receptors in neuroendocrine tumors of the breast, somatostatin has been claimed as a useful tool both for diagnostic (Octreoscan) and therapy (for metastatic disease). As for therapy, synthetic analogs show advantages versus native somatostatin, because of a longer half-life, and data from literature report encouraging results obtained by using radiolabelled somatostatin analogs. One of these is 90 Y-Dotatoc; we have already used it in patients with neuroendocrine tumors of the lung. Our algorithm for neuroendocrine tumors of the breast includes diagnostic scintigraphy with Octreoscan and receptor-mediated radiolabelled therapy with 90 Y-Dotatoc in patients with confirmed scintigraphic expression of somatostatin receptors in tumoral tissue.

In Western countries the carcinoma of the breast has an incidence of 45 cases on 1000 women. Much clinical and epidemiological evidence demonstrates that all the conditions of hyperestrogenism and extended exposure to estrogens are associated with increased incidence of malignant mammary epithelial tumor. The relationship between the exposure to ovarian hormones and mammary neoplasia has created doubts about using hormone substitution therapy in menopause. Through an analysis of the recent literature our work aims to evaluate the action of progesterone on the breast and, in particular, to study its effects on the cells of the mammary gland in association to estrogens during hormone replacement therapy in menopause.

The study of the antiproliferative action of somatostatin (ss) is important not only to understand the regulation of neuroendocrine tumours that express receptors (sst), but also non-endocrine tumours which express these receptors. We previously demonstrated the presence of sst2 in a wide panel of cell lines from human neuroblastoma. Although hypotheses have been put forward that treatment with ss or its analogs may be beneficial in oncological patients, this does not appear to be the case in neuroblastoma; patients with high sst2 levels (who are therefore sensitive to ss treatment) have per se a relatively positive outcome. Therefore, adjuvant treatment with ss is not necessary. Viceversa, patients with a poor prognosis are essentially characterized by a low expression of sst2 (and therefore are insensitive to a therapy with ss). In these patients adjuvant treatment with ss might be indicated, but would have little chance of success. Although the majority of neuroendocrine tumours expresses sst2, pancreas and prostate cancer express sst1 but not sst2, and are therefore insensitive to octreotide treatment which binds preferentially to sst2. Tumours like colorectal carcinoma and breast cancer also express sst2 in their more favourable forms. However, the concentration of sst2 in colorectal cancer is similar, if not lower than that in the surrounding normal tissue. Therefore, the probability of successful adjuvant therapy with ss is relatively low. In breast cancer, it is possible that sensitivity to estrogens may have a positive influence on the expression of sst2. This might justify clinical trials with ss in breast cancer.

Introduction: Breast scintigraphy (BS) with the bone-seeking agent 99mTc-medronate (MDP) can be usefully combined with mammography to diagnose and characterize questionable breast lumps. However this radiotracer does not seem to provide any further prognostic information about breast cancer. Therefore we investigated the prognostic yield of MDP-BS searching for correlations between scintigraphic findings and the major biological and histologic parameters., Materials and Methods: We retrospectively analyzed a series of 44 primary breast cancers. All patients had undergone 99mTc-MDP bone scan for preoperative staging, as well as conventional breast imaging. We statistically compared the cancer/background ratio (c/b index) with lesion histotype, diameter, grading, and the tissue concentrations of steroid receptors, cathepsine D, type 1 timidine kinase, pS2 and p53 proteins., Results: MDP-BS failed to depict 11 of 44 lesions (O 0.5-2 cm), detected 7 of 16 mammographically questionable lesions and correctly visualized the two multifocal cases. Also, MDP-BS depicted no metastatic axillary lymph nodes. We found no statistically significant correlation between the c/b index and the prognostic markers., Discussion and Conclusions: Differently from BS with 99mTc-MIBI, 201T1, 18F-FDG, 111In-OCT and radiolabeled estrogens and despite its good overall accuracy, MDP-BS appears to have no prognostic role. In fact, despite the well-known capability of soft tissue lesions to take up the tracer, MDP tumor trapping seems to depend mainly on the increased permeability of neovessels and on interstitial space enlargement. Few reports are available in the literature on the correlation between in vivo MDP uptake by the breast cancer and prognostic parameters. Thus, we tested possible correlations between the amount of MDP taken up by the breast cancer, histologic features and cell concentrations of some major biomarkers. The lack of any statistical significance is in agreement with the theory, and confirms the little prognostic value of MDP-BS. Nevertheless, further trials are warranted on larger series of cases to validate our personal findings.

PSA has been measured out with highly sensitive method both in liquid of mammary cysts and in cytosol of neoplastic cells. Our data point out that dysplastic, metaplastic and anaplastic breast epithelial cells produce PSA. Such production is, probably, related to expression of hormonal receptors.

PDGF AB effect on extracellular matrix protein synthesis and release by a primary culture of non transformed human mammary fibroblasts was analyzed. Primarily PDGF AB induced a modified protein distribution, with a global enhancement of secreted proteins as compared to intracytoplasmatic proteins. Furthermore, an increase in synthesis and release of the extracellular matrix proteins such as fibronectin and type I and IV collagens upon PDGF AB treatment with specific immunoprecipitation was demonstrated.

pS2 is a small protein (7000 daltons) that is prevalently expressed in human breast cancer positive for estrogen receptors: protein is, in fact, induced by estrogen stimulation. Studies indicate that pS2 protein is a marker for hormone-dependent breast tumors and that its expression is helpful in the prognosis. The presence of pS2, in fact, besides being associated in 96% of the cases to the positivities for estrogen receptors, is associated with longer overall, and disease free, survival. The pS2 protein is also expressed in normal stomach mucosa; its physiological function is unknown.

Three hundred and thirty-six patients with nipple discharge and neither physical signs at breast examination nor pathological findings at mammography, were observed from 1984 to 1988 and studied by means of ductogalactography and cytology of discharge. Of this group, 76 patients (22.6%) underwent surgery and histology. In 65/76 cases proliferative pathologic conditions were demonstrated: 51 single/multiple papillomas and 14 carcinomas. Ductogalactography suggested proliferative pathologic conditions in 59 cases and cytology of discharge showed blood in 44 patients, papillary clusters in 23, and atypical cells in 15 (both as single occurrences and in association). In cancer patients discharge appeared to be mostly spontaneous, monoductal and blood-stained. In papillomas, induced discharge was almost as frequent as spontaneous discharge, serous discharge was almost as frequent as blood-stained discharge, and milky discharge was also present. Ductogalactography confirmed its value in the diagnosis of proliferative pathologic conditions of the mammary ducts, being especially useful to detect carcinomas without palpable tumors. Cytology of discharge had poorer diagnostic significance.

Proteins phosphorylated on tyrosine are detectable by antibodies against phosphotyrosine (P-Tyr antibodies) in cells transformed by oncogene-encoded tyrosine kinases. We used P-Tyr antibodies to investigate the existence of abnormal levels of phosphoproteins in human breast cancer. Three human breast cancer cell lines (SK-BR-3, MCF-7 and CG-5) and 37 human breast cancer specimens were examined by Western blot analysis and "in vitro" kinase assay. In the SK-BR-3 cell line three major phosphoproteins of the approximate Mr of 185,000 (p185), 135,000 (p135) and 110,000 (p110) were detected. The former was identified as the HER-2 gene product by specific antibodies against HER-2 encoded protein. In the other cell lines, a product of the approximate Mr of 170,000 (p170), together with a p135 and a p110, were phosphorylated on tyrosine. P185 and p170 were shown to have an associated tyrosine kinase activity. Two proteins, comigrating with p135 and p110, were found to be highly phosphorylated on tyrosine in 50% of the breast cancer samples, but not in samples harvested from 12 human tumors of the gastro-intestinal tract. These data show that 50% of human breast cancer samples display an abnormal level of tyrosine phosphorylated proteins.

The paper reviews the studies published between 1982 and 1989 on the subject of the use of LHRH analogs in gynecological oncology. Following the analysis of hormonal changes induced by analogue therapy in premenopausal women with advanced stage breast cancer, the clinical results obtained through the clinical treatment of this neoplasia are reported. Results to date are encouraging and analogue therapy still represents an alternative to surgical sterilisation. The clinical findings in postmenopausal women are less encouraging. In both pre- and postmenopause groups, findings were correlated to the receptorial status and site of metastases. The possibility of associating analogues to other hormone replacement therapies, or to chemotherapy is then discussed. Lastly, preliminary data concerning the use of analogue therapy in advanced-stage ovary cancer are analysed. The current indications for therapy and problems still to be resolved concerning the use of LHRH analogue therapy in the context of gynecological oncology are summarised by way of conclusion.

Prompted by the observation of a case of secretory (juvenile) secretory carcinoma of the breast, the Authors review the literature on this extremely rare disease. In view of the biological characteristics of this type of tumour, the Authors maintain that to ensure radical surgery and correct staging a quadrantectomy operation combined with emptying of the axillary cavity should be performed in those cases complying with the tumour size indication (2 cm). In larger tumours they regard the Helsted operation as the only form of surgery guaranteeing an adequate degree of radicality.

Thirty non diabetic women with breast cancer and five with benign breast disease have been evaluated by oral glucose tolerance test. 40% showed a diabetic-like curve. The positive women had a metastatic disease. The positive correlation between a pathologic glucose tolerance and the metastatic disease are stressed. The conclusion is drawn that the research of a latent glycidic alteration as monitor of breast cancer evolution is useful.

This paper has been designed to review some current concepts about biochemistry, pathophysiology and clinics of androgen-binding proteins, both TeBG and cellular receptors. Some important experimental models to clarify the interactions between androgens and target cells are mentioned. Further, major clinical applications in which binding parameters were or will be of great importance are discussed in details.

Secretory periodicity of prolactin (PRL) is preserved in women with breast cancer in spontaneous or surgical menopause. Hormone titres occurring during the day may be occasionally significantly higher in respect to the ones observe in normal controls at the same hours. The periodicity features calculated by the Fourier's method show however normal indices, namely mesor (mean PRL titres in the 24 hours) phase, amplitude and frequency of oscillations.

Binding of 3H-cortisol (3H-C) and 3H-dexamethasone (3H-DX), a fluorinated glucocorticoid which does not bind to Corticosteroid Binding Globulin (CBG), was investigated in two different target tissues, human breast cancer and human leukemic lymphocytes, using a modified DCC assay method. Maximal binding to cytosol occurred, when increasing concentrations of 3H-C or 3H-DX were incubated in the presence or in the absence of an excess of cold cortisol or dexamethasone, at 0 degrees C for 1 hr or 4 hr, respectively. A 50 sec exposure to DCC was sufficient to separate bound from free labelled steroid. Data presented suggest that two different classes of glucocorticoid exist, which are differently distributed in target tissues, and may be identified on the basis of affinity for the tracer, binding specificity and thermolability.