Biomedical subjects
Publications and source records attributed to V Sacchini.
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Methods such as immunohistochemistry that have enhanced the detection of carcinoma cells in bone marrow aspirates appear to be useful in identifying patients with aggressive tumours. To detect epithelial cells in bone marrow aspirates from breast carcinoma patients, we used a pool of five different monoclonal antibodies (MAbs), which recognise 100% of breast carcinomas, together with the alkaline phosphatase method on cytospun cells obtained from sternum and iliac crest. Primary tumours were also analysed for the expression of the c-erbB-1 and c-erbB-2 oncogene products, and of two differentiation-related markers and laminin receptors. Immunoreactive cells were detected in the bone marrow of 62 of the 197 patients tested (31%) without any correlation with clinical parameters such as tumour size or lymph node metastasis, whereas a significant (P < 0.01) correlation was found with enhanced monomeric laminin receptor expression in the primary tumour. In fact, this receptor was expressed in respectively 63% and 38% of primary tumours from patients with and without immunoreactive cells in the bone marrow aspirates. Thus, the presence of immunoreactive cells in bone marrow correlates with the expression in the primary tumour of a marker of the metastatic potential of the tumour, the 67 kDa laminin receptor.
Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.
Aromatase inhibitors are a useful therapeutic option in the management of endocrine-dependent advanced breast cancer. Formestane (Lentaron) is the first irreversible aromatase inhibitor to be extensively investigated. In a phase II study to determine the effects of formestane on serum estradiol and urinary 17-hydroxycorticosteroid (17-OHCS) levels and to evaluate its clinical activity, 72 postmenopausal patients with advanced breast cancer were given formestane 250 mg intramuscularly every 2 weeks. Of 66 patients fully evaluable, 56 were estrogen receptor (ER) positive, and 43 had a disease-free interval > or = 2 years. Metastases were assessable in soft tissue (53%), bone (53%) and viscera (47%); 34 patients had 1, 32 had > or = 2 metastatic lesions. Serum estradiol levels fell significantly (p < 0.01) after 2 weeks and remained unchanged thereafter, whereas urinary 17-OHCS levels did not change during treatment. Objective responses were obtained in 19 patients (29%), of whom 8 had complete response. In relation to disease sites, similar responses were obtained in soft tissue (33%) and viscera (30%), whereas response in bone was 18%. The overall tolerability of formestane was satisfactory, and only two patients complained of local side effects. We conclude that formestane is an effective aromatase inhibitor in postmenopausal patients with hormone-dependent breast cancer, and does not interfere with adrenal steroidogenesis.
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BACKGROUND AND METHODS: Conservative surgery and radiotherapy have become well-established treatments for breast cancer, and many trials in progress are attempting to define the most acceptable type of procedure. Between 1987 and 1989 we randomly assigned 567 women with small breast cancers (< 2.5 cm in diameter) to quadrantectomy followed by radiotherapy or to quadrantectomy without radiotherapy. All patients underwent total axillary dissection. The median follow-up period was 39 months (range, 28 to 54). RESULTS: The incidence of local recurrence was 8.8 percent among the patients treated with quadrantectomy without radiotherapy, as compared with 0.3 percent among those treated with postsurgical radiotherapy (P = 0.001). However, there was a substantial effect of age: patients more than 55 years old who did not receive radiotherapy had a low rate of local recurrence (3.8 percent). The four-year overall survival was similar in the two treatment groups. CONCLUSIONS: Administering radiotherapy after quadrantectomy reduces the risk of local recurrence in women with small cancers of the breast, but radiotherapy may not be necessary in elderly women.
Chemoprevention is a new branch of oncology which aims to use chemical agents to reduce the incidence of malignant diseases in humans. On the basis of a growing mass of experimental data, it is now felt that the importance of early, precursor lesions of clinically symptomatic cancer should be recognized. Just as in cardiovascular disease, there is now major emphasis on the natural history of tumors and some authors believe that the actual disease process is carcinogenesis, rather than cancer. Indeed, as the chemoprevention of cardiovascular illness with pharmacological agents that either lower blood cholesterol or prevent platelet aggregation is widespread, the effectiveness of different chemical compounds in preventing cancer or, at least in delaying its onset, is presently under investigation. For breast cancer, various agents have been suggested as having chemopreventive effects: vitamins C and E, difluoromethylornithine, selenium, retinoids and antiestrogens. Among retinoids, 4-(N-hydroxyphenyl)retinamide, fenretinide, is at present the most promising molecule, due to its ability to concentrate in the mammary gland. Attention has recently been focussed on tamoxifen because of its effectiveness in reducing the incidence of contralateral tumors in breast cancer patients. Finally, the recent discovery of the steroid receptor superfamily is expected to stimulate further research into combination chemoprevention (the use of multiple agents to achieve synergistic effects while diminishing toxicity). As retinoids and tamoxifen both increase the synthesis or activity or transforming growth factor-beta, a cytokine which is a potent inhibitor of epithelial cell proliferation, tamoxifen and fenretinide are now proposed as the first model of combination chemoprevention in breast cancer.
Of 836 nonpalpable breast lesions histologically assessed between 1985 and 1991 at the Milan Cancer Institute, 427 were malignant (51%). Microcalcifications were present in 283 tumors (66%), alone in 200 cases or associated with a mass (72 cases) or within a focal distortion (11 cases). Several mammographic, clinical and histological features were analyzed, comparing the 283 lesions with microcalcifications with the 144 tumors represented only by nodular opacities or distortions. This was done to assess the existence of morphologic and prognostic characters differentiating the two subsets and to investigate the reliability of mammography in estimating lesion size. On the average, in our series of cases, the patients with microcalcifications were younger, had a higher rate of dense breasts and a large number of partially or totally intraductal carcinomas. In situ carcinomas were frequent and minimal lesions (< 5 mm) accounted for 43% of the whole at pathologic examination. However, the lesions with microcalcifications were associated with more positive nodes (32% vs 18%). Therefore, microcalcifications, although generally representing an early sign of cancer, appear to suggest a less favorable prognosis.
The widespread use of mammography in breast cancer screening has increased the number of non-palpable breast lesions being detected in which the differential diagnosis between benign and malignant cases requires surgical biopsy. In order to remove these mammographically identified lesions the surgeon must be guided, which is why the techniques guiding the surgeon during lesions ablation have become most important. Accurate preoperative lesion localization must be done so that the excision can be complete and with the best cosmetic result. In this report we discuss localization methods, from the simplest to the most complicated ones. The commonest method has the advantage of employing no special instruments, and it is very simple, safe and fast. It requires a skilled hand and a little training. Instrumental methods are then discussed, from the simple dedicated compressor to the stereotactic techniques and, finally, the role of ultrasonography both in preoperative localization and in cytologic biopsy. The importance of mammographic examination of the surgical specimen is also stressed.
148 consecutive patients treated by two different types of conservative surgery were objectively and subjectively evaluated for cosmetic outcome. In 73 patients, tumorectomy, axillary dissection, external radiotherapy (45 Gy) plus iridium implant (15 Gy) were performed, while in the other group of 73 patients a more extensive surgical approach was carried out: quadrantectomy, axillary dissection plus external radiotherapy (50 + 10 Gy). The appearance of the patients' breasts was analysed for symmetry by computer, and differences in symmetry were correlated with tumour location and breast size. A subjective assessment was given by a 3-member panel and the results were correlated with objective measurements. In addition, patients were asked to fill out a self-assessment questionnaire on the aesthetic result of the operated breast. Better results were generally noted in the group of patients treated by more conservative surgery. Substantial differences in the aesthetic outcome were noted between the patient's own evaluation, the computer's measurement of symmetry and the assessment of the panel of observers.
An immunocytochemical method for the detection of cancer cells, in the cell suspension obtained by scraping the surface of the surgical resection margins is described and its sensitivity compared to the conventional histology performed on random biopsies from the same margins. The reactivity of the cells with a pool of monoclonal antibodies (Mab) directed against epithelial markers indicated that in 80% of the 42 cases tested, the scraping method was adequate for the gathering of cells from the margins. The analysis of the samples using B72.3 Mab specific for tumor cells revealed that, among B72.3-positive tumor cases, 31% of breast margins contained tumor cells, whereas only 12% were histologically positive. Our results indicate that the immunocytological methodology is therefore more sensitive and should be used alongside histological examination to detect the tumor contamination in the surgical resection margins.
From June 1985 to August 1989, 344 cases of mammographic non-palpable breast lesions were operated on at the National Cancer Institute in Milan. The mammographic findings consisted of clusters of microcalcifications in 162 cases (42.1%), suspicious opacities with irregular borders in 116 cases (37.7%) and opacities containing microcalcifications in 66 cases (19.2%). The mean age of the patients was 51 years (range 31-77 years). In all patients localization was performed 1 day before the operation, introducing a self-retaining anchor wire into the mammary parenchyma. The histological findings showed benign breast disease in 184 cases (53.4%); proliferative dysplasia without atypia in 150 cases (81.5%); proliferative dysplasia with atypia in 22 cases (12%); fibroadenoma in nine and papilloma in three cases. Of 160 patients with carcinoma, 37 had non-infiltrating carcinoma: 28 of these cases (17.5%) had non-infiltrating ductal carcinoma and nine cases (5.6%) had lobular carcinoma in situ. In the 123 cases with infiltrating breast cancer the histological types were ductal infiltrating carcinoma (32.5%), lobular infiltrating carcinoma (9.8%), and 34.1% of the cases an associated or prevalent intraductal carcinoma was found. In 138 cases (85.6%) a conservative surgical procedure (quadrantectomy or more limited excision) was done, and in 22 (14.4%) cases a total mastectomy was necessary because of the extent of the disease. Axillary dissection was performed in 116 of the 123 patients with histological invasive carcinoma. Nodal metastases were found in 24 cases (20.7%), and only one node was involved in nine of the cases (37.5%), two to three nodes in nine cases (37.5%) and four to ten nodes in six cases (25%).
One thousand, four hundred and forty-six patients with carcinoma of the breast treated with Halsted mastectomy (167), Patey mastectomy (732), and conservative surgery with axillary dissection, either at the same time (340), or separately (207), were evaluated with regard to the number and distribution of axillary lymph nodes. A total of 29,378 were removed and examined, on average 20.3 per patient. The average number of nodes was 13.5 at the first level, 4.5 at the second and 2.3 at the third. The same number of nodes were removed in patients treated with extensive surgery, such as Halsted mastectomy and limited surgery such as lumpectomy and in independent axillary dissection. In 839 cases metastases were found in the axilla. The average number of involved nodes was 6.4. Out of 839 patients, the first level was the site of metastases in 828, the second level in 364 and the third in 187. When a single lymph node was involved, it was nearly always at the first level. In only 11 cases, were the second and/or third levels invaded without metastases at the first level. Therefore, the percentage of cases with skipping metastases was very low (1.3%). It appears from the present data that the spread of breast cancer to the axilla follows a regular pattern; the first level is invaded first, whilst in most cases, the second and third levels are involved only when the first is substantially affected.
Dissemination of tumor cells along the needle tract after needle aspiration biopsy has been reported in the literature, but it is an extremely uncommon event, especially when 'fine needles' (above 21 Gauge) are used. In the work presented, a patient with a mammary nodule of doubtful nature is reported. After histological evaluation the node proved to be an intra-mammary dissemination of poorly differentiated adenocarcinoma of the lung via the needle track after aspiration biopsy. The needle used was a 20 Gauge, which is not included in the fine needle category recommended by most authors. The possibility of tumor cells dissemination after needle biopsies is discussed.
In breast cancer surgery, axillary dissection is currently considered an essential step. Nevertheless, procedures commonly used include the resection of the pectoralis minor muscle and/or pectoralis nerves. Since 1984 we have performed axillary dissection by sparing both the pectoralis muscles and their nerves. In this paper we present the surgical technique. The comparison of the two groups with clinical N0 N1a assessment, the former of 103 patients submitted to this kind of surgical procedure, the latter (108 women) treated by resection of the pectoralis minor muscle, showed that the mean number of dissected lymph nodes in both procedures was superimposable.
In photodynamic therapy, systemic administration of photosensitizing agents induces cutaneous photosensitization in patients. This side-effect can be avoided by topical administration of the agents when only surface lesions are involved. A hydroalcoholic solution of tetrasodium-meso-tetraphenylporphinesulfonate (TPPS) containing Azone, a percutaneous penetration enhancer, was investigated to evaluate its photosensitizing potential in the treatment of 33 primary and recurrent neoplastic lesions of the skin. A complete remission was obtained of lesions with clinical thickness of less than 2 mm. Treatment effectiveness depends on both light and drug penetration through skin. Further studies are in progress to optimize treatment parameters.
Five hundred and thirty-nine patients with carcinoma of the breast treated with total axillary dissection and with positive axillary nodes were evaluated. The total number of lymph nodes removed was 11,082, with an average of 20.5 nodes per patient. The average number of lymph nodes at the first level was 13.8, at the second level 4.5, at the third level 2.2. The average number of nodes was 20.7 in cases treated with Halsted mastectomy, 20.9 with total mastectomy and axillary dissection, 20.3 with quadrantectomy and axillary dissection. Of 3259 metastatic nodes, 64 were site of micrometastases; 797 were partially involved, 441 were totally involved and 1957 were site of metastases with extracapsular invasion. In 314 (58.2%) the first level only was involved, in 117 cases (21.7%) metastases were present at the first and second level, whereas in 88 cases (16.3%) all the three levels were sites of metastases. Only 20 cases showed skipping distribution. In 1.5% of the cases the first level was skipped by metastases, in 0.4% the first nodes of the first level are clear the chances that metastatic nodes are present at the second and third levels are negligible. When the nodes at the first level are positive, the chances that metastases are also present at the higher levels are of the order of 40.0%.
Cutaneous photosensitization by topical administration of a porphyrin derivative has been previously reported from experimental studies. Preliminary clinical trials performed at the National Cancer Institute of Milan in the last six months have confirmed the feasibility of treating skin lesions by topical application of photosensitizers. Fourteen cases of basal cell carcinoma were treated by local administration of tetraphenylporphinesulphonate (TPPS), vehicled by azone. Later, the tumor was exposed to a wavelength of 630 nm from a dye laser. We noted complete remission, as documented by biopsies, in all tumors, with clinical thickness less than 2 mm, whereas partial remission was obtained in tumors with clinical thickness more than 2 mm. Our experience suggests the possibility of a routine treatment by this method for flat basal cell carcinoma and pre-malignant lesions, with remarkable advantages to conventional therapies. Our results have to be confirmed by increasing the number of cases and length of follow up; our short follow up does not allow us to make definitive claims regarding this therapy.