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U Veronesi

Publications and source records attributed to U Veronesi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Optimized sentinel node scintigraphy in breast cancer.

INTRODUCTION: Axillary lymph node dissection (ALND) represents an important staging procedure in the surgical treatment of breast cancer. However, it may result necessary in tumors of little dimensions because of low percentage of metastatic axillary lymph node (ALN). If a non invasive technique predicted the status of ALN, ALND procedures could be avoided. We carried out this study i) to establish the best technique to perform the lymphoscintigraphy for detecting the sentinel node in breast cancer and ii) to determine whether a clear sentinel node reliably predicts a disease free axilla. METHODS: 215 patients were submitted to the lymphoscintigraphy before surgery. Three different colloidal radiotracers with particle size ranging between < 50 and 1000 nm were injected sudermically or peritumorally. Early and late images were recorded in anterior and oblique projections and the SN was marked on the skin and biopsied using a gamma detection probe (GDP) during surgery. RESULTS: The SN was identified in 210/215 cases (97.6%). The SN accurately predicted axillary ALN status in 204/210 (97.1%) patients in whom a sentinel node was identified and in all the cases (45 patients) with tumor < 1.5 cm in diameter. In 38/101 cases with metastatic axillary nodes (37.7%) the only positive node was the SN. CONCLUSIONS: Lymphoscintigraphy can easily locate the SN in breast cancer. SN detection resulted easier when large size microcolloids were used. Subdermally administration appeared the best way of injection for palpable lesions. Breast cancer patients without clinical involvement of the axilla should undergo SN biopsy routinely and this may allow sparing complete axillary dissection when the SN is free of disease.

Antimony↗
PubMed1998

Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer.

UNLABELLED: Lymphoscintigraphy associated with radioguided biopsy of the sentinel node (SN) is well established in clinical practice for melanoma. In breast cancer, the SN concept is similarly valid, and lymphoscintigraphy is a useful method for localizing the axillary SN. The aim of this study was to optimize the lymphoscintigraphy technique in association with a gamma ray detecting probe (GDP) for identifying and removing the SN in breast cancer patients. METHODS: Two-hundred fifty patients with operable breast tumor underwent lymphoscintigraphy before surgery. Three different size ranges of 99mTc-labeled colloid particles (<50, <80 and 200-1000 nm) were used, with either subdermal (above tumor) or peritumoral injection. Early and late scintigraphic images were obtained in anterior and oblique projections, and the skin projection of the detected SN was marked. Sentinel nodes were identified and removed with the aid of the GDP during breast surgery; they were tagged separately. Complete axillary dissection followed. In 40 patients, a blue dye was also administered in addition to subdermal radiolabeled colloid to compare blue dye mapping with lymphoscintigraphy localization. RESULTS: Lymphoscintigraphy successfully revealed lymphatic drainage in 245 of 250 patients (98%). The axillary SN was identified in 240 patients (96%). SN biopsy correctly predicted axillary node status in 234 of 240 patients (97.5%). Lymphoscintigraphy and GDP detected the SN most easily and consistently when 200-1000 nm colloid was administered subdermally in an injection volume of 0.4 ml. Blue dye mapping was successful in 30 of 40 patients (75%). In 26 of these patients, the dye and lymphoscintigraphy identified the same node; in 4 cases different nodes were identified. None of these four patients had axillary disease. CONCLUSION: Lymphoscintigraphy is a simple procedure that is well tolerated by patients. Sentinel node identification is more reliable when large-size radiolabeled colloids are injected in a relatively small injection volume (0.4 ml). Use of a GDP greatly facilitates precise pinpointing and rapid removal of the SN.

Antimony↗
PubMed1997

Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes.

BACKGROUND: Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla. METHODS: In a consecutive series of 163 women with operable breast carcinoma, we injected microcolloidal particles of human serum albumin labelled with technetium-99m. This tracer was injected subdermally, close to the tumour site, on the day before surgery, and scintigraphic images of the axilla and breast were taken 10 min, 30 min, and 3 h later. A mark was placed on the skin over the site of the radioactive node (sentinel node). During breast surgery, a hand-held gamma-ray detector probe was used to locate the sentinel node, and make possible its separate removal via a small axillary incision. Complete axillary lymphadenectomy was then done. The sentinel node was tagged separately from other nodes. Permanent sections of all removed nodes were prepared for pathological examination. FINDINGS: From the sentinel node, we could accurately predict axillary lymph-node status in 156 (97.5%) of the 160 patients in whom a sentinel node was identified, and in all cases (45 patients) with tumours less than 1.5 cm in diameter. In 32 (38%) of the 85 cases with metastatic axillary nodes, the only positive node was the sentinel node. INTERPRETATION: In the large majority of patients with breast cancer, lymphoscintigraphy and gamma-probe-guided surgery can be used to locate the sentinel node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel-node biopsy routinely, and may be spared complete axillary dissection when the sentinel node is disease-free.

Adult↗
PubMed1997

Expression of p53, glutathione S-transferase-pi, and Bcl-2 proteins and benefit from adjuvant radiotherapy in breast cancer.

BACKGROUND: In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer. PURPOSE: The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990. METHODS: The expression of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered. RESULTS: After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST-pi protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers. CONCLUSIONS: Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.

Biomarkers, Tumor↗
PubMed1997

Prognostic factors for metachronous contralateral breast cancer: a comparison of the linear Cox regression model and its artificial neural network extension.

The purpose of the present study was to assess prognostic factor for metachronous contralateral recurrence of breast cancer (CBC). Two factors were of particular interest, namely estrogen (ER) and progesterone (PgR) receptors assayed with the biochemical method in primary tumor tissue. Information was obtained from a prospective clinical database for 1763 axillary node-negative women who had received curative surgery, mostly of the conservative type, and followed-up for a median of 82 months. The analysis was performed based on both a standard (linear) Cox model and an artificial neural network (ANN) extension of this model proposed by Faraggi and Simon. Furthermore, to assess the prognostic importance of the factors considered, model predictive ability was computed. In agreement with already published studies, the results of our analysis confirmed the prognostic role of age at surgery, histology, and primary tumor site, in that young patients (< or = 45 years) with tumors of lobular histology or located at inner/central mammary quadrants were at greater risk of developing CBC. ER and PgR were also shown to have a prognostic role. Their effect, however, was not simple in relation to the presence of interactions between ER and age, and between PgR and histology. In fact, ER appeared to play a protective role in young patients, whereas the opposite was true in older women. Higher levels of PgR implied a greater hazard of CBC occurrence in infiltrating duct carcinoma or tumors with an associated extensive intraductal component, and a lower hazard in infiltrating lobular carcinoma or other histotypes. In spite of the above findings, the predictive value of both the standard and ANN Cox models was relatively low, thus suggesting an intrinsic limitation of the prognostic variables considered, rather than their suboptimal modeling. Research for better prognostic variables should therefore continue.

Adult↗
PubMed1996

Effect of tamoxifen on measurements of hemostasis in healthy women.

BACKGROUND: Tamoxifen citrate is being evaluated for primary prevention of breast cancer, but this drug with estrogen-like properties may cause changes in the hemostatic system that would increase the risk of thrombosis. METHODS: Women who had undergone hysterectomy were consecutively enrolled in the placebo-controlled, randomized, double-blind Breast Carcinoma Chemoprevention Tamoxifen Study, which was designed to evaluate the efficacy of oral tamoxifen citrate (20 mg/d). Our substudy of hemostasis and lipid measurements included the first 68 consecutive women assigned to tamoxifen (n = 31) or placebo (n = 37). Blood specimens were obtained before treatment and after 1,2,4, and 6 months of treatment. Measurements included blood cell counts, lipid levels, coagulation activation markers, clotting factors, and anticoagulant and fibrinolysis proteins. RESULTS: Hematocrit and hemoglobin and platelet levels fell slightly but significantly in women treated with tamoxifen. No between-treatment differences were observed in any of the clotting factors. Naturally occurring anticoagulant proteins such as antithrombin and protein C fell slightly in women treated with tamoxifen. However, no significant changes were observed in any of the markers of activated coagulation or fibrinolysis (fibrinopeptide A, prothrombin fragment 1 + 2, thrombin-antithrombin complex, D-dimer). Total and low-density lipoprotein cholesterol levels fell significantly in women treated with tamoxifen. CONCLUSIONS: Tamoxifen induced a modest decrease in anticoagulant proteins, but without biochemical signs of activation of coagulation and fibrinolysis. Tamoxifen improved the lipid profile and induced changes in blood cell counts, which should determine an improvement in blood rheologic factors. These preliminary findings seem to justify continuation of the double-blind study in healthy women, but only direct comparison of thromboembolic complications in the 2 treatment groups will establish whether tamoxifen carries a risk of thrombosis.

Administration, Oral↗
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↗
PubMed1996

Optimal Surgical Treatment of Breast Cancer.

Large-scale, controlled trials in the 1970s and 1980s demonstrated that wide resection (for example, quadrantectomy) was as effective as mastectomy for the treatment of breast cancer up to 3 cm in maximum diameter. Conservative treatment may also be extended to larger cancers following pre-operative chemotherapy to reduce tumor mass and leave sufficiently wide resection margins to ensure oncological radicality. Quadrantectomy is an operation of curative intent, distinct from "lumpectomy" or "tumorectomy," whose main aim is to debulk the tumor mass; nevertheless, wide resection should, in most cases, be flanked by radiotherapy to sterilize the tumor bed and by complete axillary dissection to remove any metastatic nodes and provide full prognostic information. This triple approach provides a high cure rate and low relapse rate for breast cancer, while providing an acceptable cosmetic outcome; we believe it is the optimal treatment for breast cancer at the present time. Modifications include simultaneous remodeling of the affected breast if, because of tumor position, the result of conservative surgery is less than satisfactory; and use of radioguided surgery to detect the sentinel node which, if not involved, may indicate that full axillary dissection is unnecessary.

Journal Article↗
PubMed1996

Validation of p53 accumulation as a predictor of distant metastasis at 10 years of follow-up in 1400 node-negative breast cancers.

Most studies are in favor of a prognostic relevance of p53 accumulation determined by immunohistochemistry in breast cancer, but negative results are not lacking. On a series of 1400 patients with lymph node-negative cancers treated with local-regional therapy alone until relapse and with a median follow-up of 10 years, we validated the prognostic relevance for overall relapse and death of p53 accumulation observed in a pilot study and analyzed its predictivity on different adverse events. p53 protein accumulation was immunocytochemically detected using PAb1801. The case series had also been previously characterized for hormone receptor content [estrogen receptors (ERs) and progesterone receptors (PgRs)] and for cell proliferation [[3H]thymidine labeling index ([3H]dT LI)]. p53 expression, considered as a dichotomous variable with a cutoff value of 5% positive cells, significantly predicted the occurrence of overall relapse, distant metastasis, and death with an interaction with cell proliferation. p53 accumulation, cell proliferation, and their interaction term, along with tumor size and patient age, retained a predictive role for overall relapse, and together with tumor size and PgR, also for overall survival. When considered as continuous variables, we observed that the hazard of metastasis increased linearly with the increase of [3H]dT LI and decreased linearly with the increase of ER and PgR. Conversely, the hazard increased with the increase of p53-positive cells only for tumors with a [3H]dT LI lower than 7.5%. In multivariate analysis, the same prognostic factors for distant metastasis were identified when the biomarkers were considered as continuous or dichotomous variables.

Adult↗
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↗