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Biomedical subjects

U Veronesi

Publications and source records attributed to U Veronesi.

At least 109 records · Page 6Linked to original sources
PubMed1995

European School of Oncology Advisory report to the European Commission for the "Europe Against Cancer Programme" European Code Against Cancer.

A European School of Oncology Advisory Group has reviewed the European Code Against Cancer after its initial use over a 6-year period. With minor modifications, the original ten recommendations were found to be adequate, although it was agreed that an Annex was necessary to explain the scientific evidence supporting each point, and is presented herewith. Tobacco smoking clearly remains the most important cause of cancer, and now it can be quantified better than ever before. It is also clear that it is never too late to stop smoking: stopping even in middle age, prior to the onset of serious illness has a beneficial effect on life expectancy. Alcohol drinking is an important cause of cancer, and yet modest consumption levels protect against cardiovascular disease mortality. The optimal strategy seems to be a consumption not exceeding 2-3 drinks per day, although this limit may be lower for women. Increased consumption of fruits and vegetables, reduction in consumption of fatty foods, reduction of obesity and increased physical activity can all be recommended to reduce cancer risk. Exposure to excessive sunlight remains a problem which should be limited. Control of occupational cancer is a three-way partnership: legislation identifies and limits exposure to known carcinogens, employers enact the legislation and workers should respect the measures introduced. There are a number of signs and symptoms which may lead to cancer being diagnosed earlier, and patients with these should be referred to a doctor. For women, participation in organised programmes of cervical cancer and breast cancer (after 50 years of age) should lead to a reduction in mortality from these forms of cancer. The key element is organised programmes, where quality control and quality assurance are in force. These revised recommendations are the result of an agreement following advice, review and dialogue with cancer experts throughout Europe. They were approved by the European Community Cancer Experts at their meeting in Bonn on 28-29 November 1994. Their implementation by the European population should greatly reduce cancer incidence and mortality.

Alcohol Drinking↗
PubMed1995

Conservation surgery after primary chemotherapy in large carcinomas of the breast.

OBJECTIVE: The authors evaluated the utility of preoperative chemotherapy in patients with large size breast carcinoma, with a view to rendering a conservative surgical approach possible or easier. SUMMARY BACKGROUND DATA: Two hundred twenty-six of 227 patients with breast cancer involving a tumor larger than 3 cm at greatest dimension were candidates for mastectomy. They were treated with various primary preoperative chemotherapies and evaluated for surgery. METHODS: After administering various chemotherapeutic regimens, the authors reevaluated the patients' conditions clinically and radiologically to plan definitive surgical treatment. If the tumor diameter was sufficiently reduced, quadrantectomy was planned; otherwise, mastectomy was performed. Complete axillary lymph node dissection was done in all cases. RESULTS: In 90% of the cases, the size reduction was sufficient to justify breast conservation; in 10%, tumor size did not decrease enough or increased, thus mastectomy was performed. In 11.8% of the cases, the tumor was no longer identifiable at surgical inspection, and in 3.5% no tumor was found on microscopic examination. Axillary lymph nodes were free of metastases in 39% of cases. Twelve local recurrences occurred among the 203 patients treated with breast conservation (5.9%) and five among the 23 patients treated with mastectomy (21.7%). CONCLUSIONS: Primary chemotherapy can expand the indication for breast conservation to large tumors; careful attention, however, must be paid to surgical technique. The position of the tumor should be marked with tattoo points on the skin before chemotherapy. The macroscopic extent of the tumor regression must be evaluated carefully, and multiple frozen section biopsies may be needed. The margins of the resected breast should be evaluated microscopically. All microcalcifications present before treatment must be resected. The skin incision and mammary resection must fulfill criteria of radicality as well as good cosmetic outcome.

Breast Neoplasms↗
PubMed1995

Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer.

PURPOSE AND METHODS: We evaluated, in 1,800 patients with node-negative tumors treated with locoregional therapy until relapse, the competitive risks for different types of metastasis by cell proliferation (3H-thymidine labeling index [3H-dT LI]), estrogen receptors (ERs), and progesterone receptors (PgRs), and by the integration of biologic and clinicopathologic information. RESULTS: Hormone receptor status and proliferative activity of the primary tumor were not indicative of contralateral failures. Hormone receptors failed to predict the 8-year incidence of locoregional recurrence, but they were significant indicators of distant metastasis and overall survival. The latter finding was confirmed even in multivariate analysis. Conversely, cell proliferation predicted both locoregional and distant metastases and survival, regardless of patient age, tumor size, and ER and PgR status. Recursive partitioning and amalgamation analysis ascribed to cell proliferation an important prognostic role for locoregional recurrence together with patient age and tumor size. CONCLUSION: Biologic markers, in particular cell proliferation, provide information for the different types of relapse and could complement the predictive role of pathologic staging.

Adult↗
PubMed1995

[Italian study on the chemoprevention of breast cancer with tamoxifen].

There is currently a large breast cancer chemoprevention trial in Italy. The trial is based on the use of the antioestrogen tamoxifen, which is one of the most successful and most studied anticancer drugs. There is a strong evidence that this drug can prevent the growing of controlateral cancer in women previously operated for breast cancer. The chemoprevention trial using tamoxifen includes healthy women, aged 35 to 70 and hysterectomised. The participants are taking either 20 mg/day of tamoxifen or placebo for 5 years, in double blind; then they are followed-up clinically and instrumentally every 6 months for the further 5 years. The main end-point of the study is to verify the reduction of incidence and mortality from breast cancer. It was decided to recruit only hysterectomised women on the consideration that, according to some studies, tamoxifen could give an additional risk of endometrial cancer: the Italian study was especially designed with the intention of avoiding this unjustified risk.

Adult↗
PubMed1995

[Surgery of the breast: 100 years after Halsted].

In the early years of this century prevailing currents of medical opinion led to the imposition of surgery that was even more aggressive than the radical mastectomy proposed by Halsted to treat breast cancer. More recently breast conservation surgery has become established but is always accompanied by additional local treatment and often the option of systemic therapy. Studies conducted in Milan were the first to demonstrate that conservative surgery plus and adjuvant therapy such as radiotherapy is efficacious in treating small-size breast cancer. As the year 2000 approaches it has become clear that breast cancer is curable in a high proportion of cases and attention is turning to improving the aesthetic outcome of surgery, and to investigating biological and genetic factors that influence the disease.

Adult↗
PubMed1994

Effect of menstrual phase on surgical treatment of breast cancer.

1175 premenopausal women whose date of last menstrual period was known were followed up for up to 20 years (average 8 years) after surgery for breast cancer. 525 patients were in the follicular phase and 650 in the luteal phase. We observed 192 unfavourable events among patients operated on during the follicular phase (36.6%) and 192 among patients operated on during the luteal phase (29.6%). The effect of phase was restricted to patients with positive axillary nodes. The 5-year relapse-free survival was 75.5% in 246 node-positive patients operated on during the luteal phase and 63.3% in 190 node-positive patients who had surgery during the follicular phase. The hazard ratio at Cox multivariate analysis was 1.329 for all patients (p = 0.006) and 1.431 for node-positive patients (p = 0.03). In our study, premenopausal patients with breast cancer and positive axillary nodes operated on during the luteal phase had a significantly better prognosis than patients operated on during the follicular phase. It may be that the processes of cell metastases, such as loss of adhesiveness, may be enhanced by high concentrations of unopposed oestrogens or by reduced activity of natural killer cells during the first half of the menstrual cycle.

Adult↗
PubMed1994

The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients.

BACKGROUND: The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. PURPOSE: We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. METHODS: The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. RESULTS: A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events. CONCLUSION: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.

Breast Neoplasms↗
PubMed1994

Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide.

Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized in the United States in the late 1960s. This retinoid shows a preferential accumulation in breast instead of liver, is effective in the inhibition of chemically induced mammary carcinoma in rats, and has proved to be less toxic than many other vitamin A analogues. The Milan Cancer Institute has put a particular effort in this molecule in both the experimental and clinical fields. We have demonstrated, in animals and humans, that fenretinide induces a rapid reduction of retinol plasma concentration, that its blood levels remain constant during administration for as long as 5 years, and that the drug is able to accumulate in the human breast. To date, 2969 stage I breast cancer patients have been randomized to evaluate the efficacy of this retinoid to prevent contralateral new primaries, 709 subjects have been accrued in a prevention trial of basal cell carcinoma of the head and neck, and 153 patients entered a study the preliminary results of which already show the capability of fenretinide to prevent recurrences and new localizations of oral leukoplakia. Further studies on fenretinide will be aimed at evaluating its preventive efficacy in superficial bladder and prostate cancers and at exploring possible synergism with tamoxifen and interferons in breast cancer and skin cancer, respectively.

Anticarcinogenic Agents↗
PubMed1994

Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer.

At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed.

Aged↗
PubMed1994

Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features.

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.

Age Factors↗
PubMed1994

Prognosis based on primary breast carcinoma instead of pathological nodal status.

In breast cancer patients, prognostic information required to plan post-surgical therapy is obtained mainly through axillary dissection. This study was designed to establish a new prognostic score based solely on parameters of the primary tumour as an alternative to axillary surgery in assessing prognosis. Eight different prognostic factors, including menopausal status, tumour size, grading, lymphatic invasion, desmoplasia, necrosis, c-erbB-2 and laminin receptor expression, were evaluated retrospectively on a large series of primary breast carcinoma patients. From multivariate analysis, four independent parameters were selected and examined, alone and in combination, for their prognostic potential. These parameters were used to generate a prognostic score that was analysed retrospectively in 467 N0-N1a patients to determine its predictive value for survival. The score, which includes variables such as tumour size, grading, laminin receptor and c-erbB-2 overexpression, was established based on the number of negative prognostic factors: score 1 refers to cases in which all four parameters reflect a good prognosis, scores 2 and 3 refer to tumours in which, respectively, one or two of the four parameters reflect a poor prognosis, whereas score 4 refers to tumours with three or four poor prognosis factors. Analysis of the overall survival of the four score groups shows that patients with score 1 tumours (22% of the total) had the best prognosis with a 15 year survival of 82%, patients with score 2 and 3 had an intermediate prognosis, whereas score 4 patients had the poorest prognosis with a 15 year survival of only 38%. Moreover, survival in the N+ score 1 cases was found to be longer than that in the total N- patients. Our data suggest that the primary tumour score provides more reliable prognostic information than pathological nodal status, and that axillary dissection can be avoided in a large number of patients.

Breast Neoplasms↗
PubMed1994

Protection against doxorubicin-induced alopecia in rats by liposome-entrapped monoclonal antibodies.

Alopecia is a common side effect of several anti-cancer drugs, including doxorubicin. Based on our recent observation that a monoclonal antibody (MAD11) directed against this anthracycline inhibits the systemic toxic effect of the drug in mice, we investigated the possibility that MAD11 administered topically might protect against doxorubicin-induced alopecia. In 31 of 45 young rats treated intraperitoneally with doxorubicin, alopecia was completely prevented by topical treatment of the skin with liposome-incorporated anti-doxorubicin monoclonal antibody. This type of treatment might find relevance in preventing anthracycline-induced alopecia in cancer patients. Our findings also provide the first demonstration that liposome-entrapped monoclonal antibodies are capable of penetrating the stratum corneum of the skin without losing their function.

Alopecia↗
PubMed1994

Surgical pitfalls after preoperative chemotherapy in large size breast cancer.

Preoperative chemotherapy in 226 women with large breast cancers reduced tumour size sufficiently for breast conservation surgery, according to our criteria, in 203 patients (90%). After 50 months' mean follow-up there were 13/203 local relapses (5.3%). This approach is therefore effective but only if the breast can be conserved with good aesthetic result, otherwise mastectomy plus reconstruction is preferable. The type of surgery must be decided during operation after careful assessment of tumour regression, resection margins, tumour size in relation to breast size and extent of microcalcifications.

Antineoplastic Agents↗
PubMed1993

N-(4-hydroxyphenyl)retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid.

N-(4-Hydroxyphenyl)retinamide (HPR) is a synthetic retinoid of particular clinical interest in cancer chemoprevention. We have examined the in vitro effects of HPR on lymphoid and myeloid malignant cell lines and found that at concentrations between 10(-5) and 3 x 10(-7) M it induces a dose-dependent growth inhibition (the peak plasma concentration in patients treated with HPR is 1 to 2 x 10(-6) M). The antiproliferative effect of HPR was, in all cell lines except K422, more potent than that induced by an equimolar dose of all-trans retinoic acid (RA). Also, this effect was irreversible on HL60 and DoHH2 cells that had been exposed to HPR (3 x 10(-6) M) for 24 h, but reversible on Raji and DHL4 exposed to the retinoid for 48 and 72 h, respectively. Time-course growth analysis showed that HPR at 3 x 10(-6) M or below induces a rapid fall of thymidine uptake and viability (> 90%), whereas between 10(-6) and 3 x 10(-7) M exhibits cytostatic effects. Interestingly, the RA-resistant HL-60R and NB306 cells, characterized by a point mutation in the retinoic acid receptor (RAR) and by the loss of the pml/RAR protein, respectively, were, like the parental RA-inducible HL-60 and NB4 cell lines, fully responsive to HPR, thereby suggesting that HPR and RA could act through different receptors or pathways. DNA flow-cytofluorimetric analysis revealed that HPR does not block cells in a specific phase of the cell cycle but triggers programmed cell death or apoptosis. This phenomenon was evidenced both by the visualization, on gel electrophoresis, of fragmented DNA, and by the "in cell" enzymatic labeling of DNA breaks with fluorescent dUTP. With the latter method, apoptotic cells become detectable by 6 h following exposure to 3 x 10(-6) M HPR. Ultrastructural examination of HPR-treated samples showed cells with chromatin compaction and cytoplasm condensation, characteristic of apoptotic cells. In conclusion, our study demonstrates that HPR suppresses malignant cell growth and induces apoptosis at pharmacologically relevant doses. The differential responsiveness by a number of cell lines, especially HL-60R and NB306, to HPR and RA indicates that these compounds may act through different receptors. The clinical use of HPR, particularly in retinoic acid-unresponsive acute promyelocytic leukemia patients, is suggested.

Apoptosis↗