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U Veronesi

Publications and source records attributed to U Veronesi.

At least 19 recordsLinked to original sources
PubMed1996

Results of a breast-cancer-surgery trial compared with observational data from routine practice.

BACKGROUND: The strength of randomised controlled trials (RCTs) is that they allow investigators to draw reliable inferences about treatment differences; physicians can then make a choice between different options. Their weakness is that they are conducted on a set of patients who cannot be regarded as a random sample from the population that will be treated outside the trial. Observational data collected in a prospective clinical database may provide more realistic estimates. METHODS: At the Istituto Nazionale de Tumori of Milan an RCT was started in 1973 (MI1) in which Halsted mastectomy was compared with quadrantectomy plus axillary dissection and radiotherapy (QUART), a breast conserving treatment, for "early-stage" primary breast cancer. In addition, a prospective clinical database was established to collect, in standard format, information on all women undergoing breast conservation thereafter and followed up at the Institute. 1760 women were treated with QUART, 350 of them being accrued in the years 1973-80 in the context of the MI1 trial. The remaining 1408 received QUART after the MI1 trial, up to December, 1984. RESULTS: In the years after the trial, the criteria for use of QUART became more liberal. However, after adjustment for baseline characteristics, out-trial patients fared no worse than trial patients in terms of survival or distant metastasis. Out-trial patients did have a slightly higher rate of local recurrence, probably because of subtle and multiple changes in the surgical procedures since the time of the trial. INTERPRETATION: The results of QUART in out-trial patients resembled those reported from research settings. In this instance, the results of clinical trials did not exaggerate the benefits obtainable in routine practice.

Adult↗
PubMed1996

Breast cancer surgery: a century after Halsted.

In the early years of this century prevailing currents of medical opinion led to the imposition of surgery 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 flanked by additional local treatment, and often by systemic therapy. Studies conducted in Milan were the first to demonstrate that conservative surgery plus an 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 the surgery, and to investigating the biological and genetic factors that influence the disease.

Breast Neoplasms↗
PubMed1995

Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events.

BACKGROUND: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment. PURPOSE: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment. METHODS: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quadrantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches. RESULTS: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (< 2 years) local failure predicted for distant metastases compared with later failure. In local failure patients, the 5-year survival rate was 69% from failure. CONCLUSIONS: Local recurrences and distant metastases are partially independent events that occur at different times; several predicting factors also differ. However, women with local recurrences have increased risk of distant metastases. In particular, women 35 years old or younger at first diagnosis who had initial peritumoral lymphatic invasion and local recurrence within 2 years are at high risk for distant spread. For recurrence in cases with an extensive intraductal component or where initial local surgery was possibly inadequate, women are at lower risk.

Adult↗
PubMed1995

Controlled clinical trials with fenretinide in breast cancer, basal cell carcinoma and oral leukoplakia.

We are conducting three randomized studies (breast cancer, basal cell carcinoma, oral leukoplakia) and report our methodological approach and accrual here. The aim of the breast cancer study is prevention of a contralateral primary lesion in women already treated for breast cancer; the aim of the basal cell carcinoma study is prevention of recurrences or new occurrence after surgical resection; and the aim of the oral leukoplakia study is prevention of recurrences and new occurrence after CO2 laser resection. The studies were planned according to a randomized design with an intervention arm vs a no-treatment arm. Patients in the intervention group receive 4-HPR at a dose of 200 mg po. The duration of treatment is five years in the breast cancer study, and one year in the basal cell carcinoma and oral leukoplakia studies. The breast cancer study started in March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the control group). Of 2,849 evaluable patients, 867 completed the first five years, 1,142 are still ongoing, and 840 patients have interrupted the study for various reasons. Follow-up is ongoing. The basal cell carcinoma study started in January 1990. As of January 1994, a total of 786 patients had entered the study; 760 were evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients in the study, 568 completed the first year, 62 are ongoing and 130 discontinued for various reasons. The study is ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticarcinogenic Agents↗
PubMed1995

Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients.

Breast conservation has become well-established in the treatment of early mammary carcinoma. However, a standardised treatment modality has not emerged. We have analysed the data from 1,973 patients treated in three consecutive randomised trials by four different radiosurgical procedures: Halsted mastectomy, quadrantectomy plus radiotherapy, lumpectomy plus radiotherapy, and quadrantectomy without radiotherapy, to compare the outcomes of these procedures in terms of local recurrence rate and overall survival. Eligibility criteria were similar in the three trials, and comparability between the four subgroups was excellent. Median follow-up for all patients was 82 months. The annual rates of local recurrence varied markedly according to the treatment. Patients treated with Halsted mastectomy and quadrantectomy plus radiotherapy had low annual rates of local recurrence (0.20 and 0.46, respectively) while both lumpectomy plus radiotherapy and quadrantectomy without radiotherapy had significantly higher rates (2.45 and 3.28, respectively). Patients under 45 years of age had a much higher incidence of local recurrences, while in women over 55 years local recurrences were much less frequent. Overall survival curves were identical in the four groups of patients, so that the three breast conserving radiosurgical procedures had the same survival rates as Halsted mastectomy. However, local recurrence rates were markedly influenced by the treatment method, patient age and specific histological features.

Adult↗
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↗
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↗