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Aim: To evaluate feasibility, tolerability and cosmetic outcome of intra-operative radiation therapy (IORT) as an exclusive post-surgery treatment of early stage breast cancer., Patients and Methods: From October 2008 to October 2009 30 patients underwent wide breast cancer excision or quadrantectomy followed by IORT on tumor bed with accelerated electrons at the dose of 21Gy. The characteristics of the patients were: ductal breast cancer or invasive lobular cT1, cT2 ≤ 2,5 cm, cN0, G1-2, age over 35 years, M0., Results: The average age was 51.7 (range 38 - 75) with an average follow up of 11.7 months (range 6 - 18). The pathologic stage of the lesions resulted pT1 in 29 cases (96,6%), in particular: one case pT1a (3,3%), 21 cases pT1b (70,0%) and 7 cases pT1c (23,3%). One case (3,3%) was pT2 with a diameter of 2.5 cm. The grading was G2 in 20 cases (66,6%) and G1 in 10 cases (33,3%). The toxicity, evaluated according to the EORTC-RTOG criteria, was G0 (33.3%) in 10 cases, G1 (63,3%) in 19 cases, G2 in one case (3,4%); there was no G3 toxicity. The time needed for a complete healing of the wound was less than 10 days in 96,7% of the cases, with one case of limphocele (3,3%). There were no infections of the surgical wound nor any mastitis, neither in the treated quadrant nor in the other ones. We observed a light fibrosis in 5 cases (16,6%), moderate in 2 cases (6,6%) but never severe. Cosmetics, evaluated in four levels, according to Danoff et al., was excellent in 3 cases (43,3%), good in 15 cases (50%), sufficient in 2 cases (6,7%), never insufficient. As regards local control, there was no local relapse. The global survival was 100%., Conclusions: The IORT in early breast cancer, at the doses used in this study, proved itself as a secure technique, repeatable, with limited complications. The advantages of its use are the possibility of a direct control, by the surgeon and the radiotherapist, of the structures to treat and those to protect; the absence of time needed for cellular repopulation between surgery and radiotherapy; a good cosmetic outcome; and logistic advantages. It is necessary to have a long term follow up to evaluate the efficacy in terms of long term cosmetic and local control.

Thanks to a retrospective analysis of the first 250 cases of sentinel lymph nodes in breast cancer assessed by the authors over the period from October 1998 to December 2000 in the light of a careful review of the literature, it has been possible to establish the importance of careful patient selection, strict compliance with the execution technique and, above all, the need for an adequate learning curve, before the procedure is used in particular protocols and/or in routine clinical practice in the near future. In particular, the training should first of all ensure that all personnel involved, i.e. surgeons, nuclear medicine specialists, and histopathologists, should attend specific courses at qualified Institutions followed by the actual management of a certain number of consecutive cases. In order to perfect the methodology and organisation, a preliminary study in a group of patients at different stages of evolution of the disease is recommended (50 cases in the study population reported). The next phase should include a group of highly selected patients, numbering at least 50-100. The training may be considered complete when in at least 20 cases, an identification rate of at least 90% is achieved with an incidence of false negatives of not more than 5%. In the authors' experience, these results were reached after 100 selected patients, and were later consistently confirmed after a further 50 cases.

The prognosis of soft tissue sarcomas has dramatically improved over the past few decades thanks to the use of increasingly suitable multidisciplinary therapeutic approaches. An assessment of the results of our series of 21 patients, carried out in the light of the most recent literature data, has led us to revise our approach to a number of problems regarding the natural history, the nosographical classification and the therapy of these cancers. This type of tumour arises in a muscle compartment and then spreads proximally and distally within the compartment without involving adjacent structures, except in a relatively advanced phase, while as regards remote metastases the preferential diffusion route is via the bloodstream. Thorough assessment of the clinical and morphological characteristics is essential for adequate treatment: echotomography, CT, and MRI are particularly useful in preoperative staging; a microscopic examination should always include precise classification and accurate assessment of the tumour grade. Surgical management consists in extensive en bloc resection, followed by radiotherapy in the event of unclear margins and/or high grade tumour even when dealing with small sarcomas. The main indications for chemotherapy are locally advanced cases or cases with distant metastases. Thanks to these therapeutic approaches today, good results can be achieved, with 5-year survival rates of 80 and 67%, respectively, in stages I and II, and of 12 to 50% in the more advanced stages.

The role of proliferation-related markers on breast cancer pathogenesis has been only occasionally investigated. The immunocytochemical expression of P53 and Bcl-2 (using PAb1801 and anti-bcl-2 monoclonal antibodies) and cell proliferation (evaluated as the H-3-thymidine labeling index [H-3-dT LI]) were determined on 62 benign breast lesions at different risk. Accumulation of the P53 protein was never observed; Bcl-2 was detected in 50% of cases and it was unrelated to biologic and clinicopathologic features. Median H-3-dT LI was about three times lower than that observed on large series of invasive breast cancer. It was only slightly higher in lesions from patients younger than 35 years or with a positive family history than in those under 35 or with a negative family history and appeared unrelated to histology or risk classification. Such findings indicate that the investigated biomarkers fail to identify women at increased risk for breast cancer.

Twenty-one operable breast cancer patients were treated with interferon-beta (IFN-beta) at the dosage of 3 x 10(6) IU every other day for a median time of 16 days. Estrogen receptors (ER), progesterone receptors (PgR), labelling index (LI) and DNA ploidy were evaluated on tumour tissue obtained during diagnostic biopsy and surgery, before and after treatment respectively. The study showed a statistically significant rise of ER (18 out of 21 evaluable cases) (p = 0.04) and no influence on ploidy status (8/21) in all evaluable samples. We also noticed a rise of PgR (18/21) and a decrease of LI (10/21 cases), but they were not statistically significant. Moreover, in the patients in whom both determination of ER and LI was possible (10 cases), a significant inverse correlation between the differences pre- and post-treatment was observed (p = 0.016). These preliminary results induce us to study a greater number of patients with the aim to confirm the biological effects of IFN-beta on ER, to clarify the trend of the rise of PgR and the decrease of LI and to analyse the relationship between these parameters.

In a large number of patients suffering from breast carcinoma the surgeon is still forced, for strictly technical reasons and/or by the patient's choice, to perform a radical operation that psychologically and practically compromises the quality of life of the patient, in varying degrees from patient to patient. The authors have analyzed the main characteristics of BR from the esthetic-functional, psychological, and oncological points of view, in the light of a careful examination of the literature and of the data relating to a sample group of 500 BR treated according to a protocol in which BR has been included, with times and modalities depending on the histological type of tumor and the level of local evolution of the disease. The variety of BR techniques available is such as to permit this option in a great variety of cases. Whenever possible, immediate BR, with placement of a breast prosthesis at the same time or after positioning a tissue expander, is to be preferred. If additional skin or muscle is needed, BR is to be performed at a later time by means of more complex techniques (latissimus dorsi myocutaneous flap plus prosthesis, TRAM flap, free flap). When performed after adequate evaluation and in a technically valid way, BR gives good esthetic and psychological results, has a low incidence of complications or sequelae, and does not affect the natural history of the disease; in particular, BR does not change the percentage of local recurrence or its early diagnosis and allows adequate multidisciplinary treatment.

The efficacy of the addition of prednisolone to tamoxifen as adjuvants to mastectomy in patients with primary breast cancer who were at a high risk of recurrence was investigated in a randomized trial. Primary carcinomas were collected from a series of 169 patients with loco-regional disease, undergoing mastectomy. The activities of alpha-glycerolphosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the carcinomas were estimated biochemically and the ratio of the two enzymes was used to as the parameter to determine the risk of recurrence. 116 patients with a high risk of recurrence within five years of mastectomy were then randomized to either tamoxifen (2x20 mg/day) or tamoxifen+prednisolone (3x2.5 mg/per day) until recurrence. The patients are currently followed quarterly. The data were analysed at a median follow-up of 26 months (range 7-62 months). The probabilities of both disease-free and overall survival were not significantly different in either arm of the trial, indicating that there is no advantage in combining prednisolone with the antioestrogen. Recently, similar findings in terms of response have been reported for patients with metastatic disease treated with the same combination, raising doubts over the role of prednisolone in the management of patients with endocrine treatments.