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We describe a novel multicomponent graphene nanostructured system that is biocompatible, and has strong NIR optical absorbance and superparamagnetic properties. The fabrication of the multicomponent nanostructure system involves the covalent attachment of 3 components; Fe(3)O(4)(Fe) nanoparticles, PAMAM-G4-NH(2) (G4) dendrimer and Cy5 (Cy) on a graphene oxide (GO) surface to synthesize a biologically relevant multifunctional system. The resultant GO-G4-Fe-Cy nanosystem exhibits high dispersion in an aqueous medium, and is magnetically responsive and fluorescent. In vitro experiments provide a clear indication of successful uptake of the GO-G4-Fe-Cy nanosystem by MCF-7 breast cancer cells, and it is seen to behave as a bright and stable fluorescent marker. The study also reveals varied cellular distribution kinetics profile for the GO nanostructured system compared to free Cy. Furthermore, the newly developed GO nanostructured system is observed to be non-toxic to MDA-MB-231 cell growth, in striking contrast to free G4 dendrimer and GO-G4 conjugate. The GO-G4-Fe-Cy nanostructured system characterized by multifunctionality suggests the merits of graphene for cellular bioimaging and the delivery of bioactives.

A moderately differentiated grade 2 invasive ductal carcinoma was diagnosed in the right breast of an 81-year-old woman. The uniform nuclear profiles and moderately abundant granular cytoplasm suggested a neuroendocrine tumour and a Grimelius stain was positive. Neurone specific enolase, synaptophysin and somatostatin stained positively, and casein was interpreted as positive although with some background staining. By electron microscopy, tumour cells possessed desmosomes, tonofibrils, intercellular lumina, lamina and dense granules. Rounded dense granules 160-480 nm in diameter resembled neuroendocrine granules. They were found in both luminal and basal areas. Fewer and much larger ('giant') granules had a rounded profile and were up to 5 microm across. The smaller cytoplasmic granules were mostly Grimelius-positive while giant granules were negative. The smaller granules were also uranaffin-positive, but no uranaffin-positive cytoplasmic giant granules were encountered. Both small and giant granules were observed in lumina, and here both were uranaffin-positive. Intraluminal giant granules had a substructure of small pale lipid-like lacunae, and some had irregular profiles. The exceptional size of these exocrine granules is emphasised, and the nature of both the small and giant granules discussed in this amphicrine carcinoma.

Prognostic factors predicting for breast recurrence following breast conserving surgery and radiotherapy have been identified in a prospective randomised trial comparing two different radiotherapy techniques. The first used megavoltage radiation to encompass the whole breast and regional nodes (WF group). The second used an electron field directed to the tumour bed only (LF group). With a median follow up of 8 years survival in both groups was the same (72%). There was an increased rate of breast recurrence in the LF group: 25%, compared to the WF group: 13% (P = 0.00008), expressed in actuarial terms at 8 years. In a multivariate analysis of factors predicting for breast recurrence, once the difference in treatment technique is allowed for, only two factors were found to be significant: histological grade (P = 0.013) and lymphovascular invasion in the histological specimen (P = 0.037).

In 1990, we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were randomized to have radiotherapy to the tumour bed only (limited field, LF group) or to the whole breast and regional nodes (wide field, WF group). No adjuvant systemic therapy was prescribed. At the time the median follow-up was 37 months. We present the updated results after an extended median follow-up of 65 months. The overall survival is 72.7% and 71.2% for the LF and WF groups respectively. The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF) for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma, the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of 21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature. This trial also shows the lumpectomy with limited field irradiation is feasible, albeit with a higher breast recurrence rate; the latter could be reduced by improved selection and refinement of the technique.

Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII-related antigen and CD 34 (QB-END/10). Two breast tumours showed binding of UEA-1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication.

Patients with a clinically palpable breast carcinoma, 4 cm or less in diameter, and with no palpable nodes in the axilla were prospectively entered into a randomized clinical trial. A total of 713 patients were registered between November 1982 and December 1987, of whom 708 are evaluable at a median follow-up of 37 months. Following excision of the primary tumour, patients were randomly allocated either to have radiotherapy to the affected quadrant only (LF group) or to the whole breast and regional lymph node areas (WF group). No adjuvant hormone or chemotherapy was prescribed. The primary tumour was reported as completely excised histologically in 80% of cases, incompletely excised in 10%, and no estimate was possible in 10%. At six years from first randomization, 96% of the WF group and 92% of the LF group have remained free of breast recurrence (94% and 87% actuarial breast recurrence-free survival at 5 years). Part of the difference may be explained by the 20% recurrence rate in the breast for lobular carcinomas treated within the LF group. Of the WF group 14 patients (4%) developed recurrent disease in the axilla, compared to 50 patients (14%) in the LF group (95% and 86% actuarial axillary recurrent-free survival at 5 years). Patients with primary tumours histologically 1 cm or less in diameter had a 98% actuarial 5-year survival compared with 74% for those with tumours measuring 2 cm or more in diameter (P = 0.003). Continued follow-up of these patients will provide further information on the factors governing local/regional recurrence.