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U Veronesi

Publications and source records attributed to U Veronesi.

At least 127 records · Page 7Linked to original sources
PubMed1993

p53 as an independent prognostic marker in lymph node-negative breast cancer patients.

BACKGROUND: At present, most decisions concerning the use of adjuvant therapy in lymph node-negative breast cancer patients are made on the basis of traditional factors such as tumor size, nodal status, and histopathologic features. However, prognostic factors are being investigated that could identify high-risk groups and that could better address treatment efforts for those patients. Identification of more accurate prognostic markers, such as the expression of the mutant p53 protein encoded by the p53 (also known as TP53) tumor suppressor gene, that are reproducible, easily assessable, and independent in predicting clinical outcome would have a beneficial impact on cancer treatment decisions. PURPOSE: Our purpose was to analyze the predictive relevance of mutant p53 protein expression on 6-year relapse-free and overall survival in node-negative breast cancer patients in relation to menopausal status, tumor size, cell kinetics, and estrogen receptor status. METHODS: Expression of mutant p53 protein was detected by an immunohistochemical technique using a 1:50 dilution of PAb1801 monoclonal antibody on paraffin-embedded tumor specimens obtained from 256 axillary lymph node-negative breast cancer patients, with long-term follow-up (median, 72 months). The [3H]thymidine labeling index, a measure of cell kinetics, was evaluated on histologic sections after fresh tumor tissue was labeled with [3H]thymidine. Estrogen receptor status was determined by the dextran-coated charcoal absorption technique. Statistical comparisons were made for levels of p53 protein expression, [3H]thymidine labeling index, estrogen receptor status, tumor size, and menopausal status with respect to 6-year relapse-free survival and overall survival. RESULTS: Overexpression of the p53 protein, defined as the presence of more than 5% positive cells, was detected in 113 (44%) of 256 tumors. Odds ratios (ORs) for multiple regression analysis of 6-year relapse-free survival were significantly higher for p53 (OR = 3.24; 95% confidence limits [CL] = 2.01-5.23) and [3H]thymidine labeling index (OR = 1.92; 95% CL = 1.19-3.12), both of which appeared to be the most relevant indicators of relapse, than for tumor size (OR = 1.49; 95% CL = 0.94-2.38) and estrogen receptor status (OR = 0.91; 95% CL = 0.55-1.51). Overexpression was found to be unrelated to menopausal status. CONCLUSIONS: Immunohistochemically detected p53 overexpression is an independent marker for shortened 6-year relapse-free and overall survival in node-negative patients with resectable breast cancers. Based on these findings, p53 overexpression should be used with other established prognostic factors, such as [3H]thymidine labeling index and estrogen receptor status, to further refine the prognostic assessment of node-negative breast cancer.

Adult↗
PubMed1993

Radiotherapy after breast-preserving surgery in women with localized cancer of the breast.

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.

Breast Neoplasms↗
PubMed1993

Mammographic patterns in breast cancer chemoprevention with fenretinide (4-HPR).

In 1987 a chemoprevention trial was started at the Istituto Nazionale Tumori of Milan to evaluate the efficacy of fenretinide or 4-HPR (an effective agent against carcinogen-induced epithelial tumours in experimental animals) in reducing the incidence of contralateral breast cancer in women previously treated for an early breast cancer (pT1, pT2, N-). Patients were randomised into two groups: 4-HPR 200 mg/day vs. no treatment. We reviewed the mammograms of 149 patients who received 4-HPR for at least 4 years to examine whether changes seen in the mammary glands of rats could also be seen in women. For each patient, at least five mammograms (one at baseline and four annual controls) of the contralateral breast were classified according to Wolfe's parenchymal patterns (N1, P1, P2, DY). With the daily dosage of 200 mg and after follow-up, no changes in mammographic patterns were observed.

Adult↗
PubMed1993

Retinoids, breast cancer and NK cells.

N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid which reduces the incidence of experimental tumours in animals and has been chosen for its weak toxicity to be tested as a chemopreventive agent in humans. The mechanism of antineoplastic action is still unknown but a possible immunoenhancing effect may be postulated. We investigated the NK activity of PBMC from a group of women treated with 4-HPR as a part of a large scale randomised phase III trial on chemoprevention of contralateral disease in mastectomised women. After 180 days of treatment the NK activity was augmented 1.73 times as compared to that of patients given a placebo. The NK activity of PBMC from 4-HPR treated women is maximised, being higher than the basal and even the rIL-2 or alfa-rIFN stimulated activity of controls. For this reason in the majority of cases it cannot be further augmented by incubation with either rIL-2 or alfa-rIFN in vitro. The increased NK activity of 4-HPR treated women is not due to an enhanced production of endogenous IL-2, because PBMC cultures from patients treated with 4-HPR or placebo, incubated in vitro with a panel of different stimulators (recall antigens, PHA, allogeneic and xenogeneic cells) produce similar amounts of IL-2. The functional activity, but not the number of NK cells is increased in 4-HPR treated women. The mechanism by which 4-HPR stimulates NK activity is not a function of direct action on NK cells. Indeed incubation of PBMC from blood donors with 4-HPR or its major metabolite N-(4-methoxyphenyl) retinamide (4-MPR) does not modify their natural cytotoxicity.

Adult↗
PubMed1993

Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations.

PURPOSE: Monitoring of fenretinide (4HPR) levels, kinetics, and effects on retinal was performed in patients who participated in a phase I trial and who continued to be treated for 5 years as phase III trial patients. Accumulation of 4HPR in the breast was also assessed. PATIENTS AND METHODS: Plasma concentrations of 4HPR, of its main metabolite N-(4-methoxyphenyl)retinamide (4MPR), and of retinol were assayed by high-performance liquid chromatography (HPLC) in breast cancer patients treated orally with 4HPR 200 mg/d for 5 years with a 3-day drug interruption at the end of each month. RESULTS: 4HPR, at 200 mg/d, resulted in average 4HPR plasma levels of approximately 1 mumol/L, which remained steady and caused steady retinol level reduction; 4MPR levels, similar to those of 4HPR, slightly but significantly increased during the first 35 months, but at 5 years they were similar to those at 5 months. During daily treatment, baseline retinol concentrations were reduced by 71%; after a 3-day drug interruption, all patients recovered and the mean reduction was 38%. After discontinuation of 5-year treatment, 4HPR and 4MPR half-lives (t1/2 beta) were 27 and 54 hours, respectively, similar to those reported after 28 daily treatments. After 6 and 12 months, the concentrations of 4HPR were at the limit of detectability (0.01 mumol/L), whereas those of 4MPR were five times higher. Baseline retinol concentrations were already recovered after 1 month. Accumulation of this retinoid in the breast was evidenced by concentrations of 4HPR and 4MPR in nipple discharge and in breast biopsies that were 10 and 20 times higher, respectively, than those found in plasma. CONCLUSION: 4HPR, at 200 mg/d for 5 years, resulted in constant drug plasma levels and constant retinol level reduction. After treatment interruption, 4HPR plasma concentrations decreased at the limit of detectability at 6 months and baseline retinol plasma concentrations were recovered after 1 month.

Adult↗
PubMed1993

Cell kinetics as a predictive factor in node-positive breast cancer treated with adjuvant hormone therapy.

PURPOSE: The fraction of cells that incorporate 3H-thymidine (3H-dT labeling index [3H-dT LI]) proved to be a prognostic indicator in patients with node-negative and node-positive resectable breast cancers treated with locoregional treatment alone or with adjuvant combination chemotherapy. In this study, we assessed the prognostic role of 3H-dT LI alone and in association with other pathologic and biologic variables in a series of 249 women with node-positive breast cancers treated with adjuvant endocrine therapy. PATIENTS AND METHODS: All patients were postmenopausal, had resectable estrogen receptor-positive (ER+) tumors, and had received tamoxifen for at least 1 year after radical or conservative surgery plus radiotherapy. The median follow-up duration was 48 months. RESULTS: The 4-year relapse-free survival (RFS) rates were significantly lower for patients with large tumors (> 2 cm), with more than three positive lymph nodes, with low (< 150 fmol/mg proteins) ER content, without progesterone receptors (PgRs), or with rapidly proliferating tumors. 3H-dT LI provided prognostic information independent of axillary node involvement, ER content, PgR status, and tumor size, with an estimated odds ratio (OR) higher than that of tumor size, lymph node involvement, or ER concentration. In addition, 3H-dT LI and PgR in association were able to identify patients with different risks of relapse within subsets of tumors with less or more than three positive nodes. CONCLUSION: 3H-dT LI provides prognostic information complementary to PgR, tumor size, lymph node involvement, and ER content in the prediction of RFS of postmenopausal patients with node-positive, ER + resectable tumors treated with adjuvant hormone therapy.

Aged↗
PubMed1992

Breast cancer (3).

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Antineoplastic Agents↗
PubMed1992

Breast cancer (1)

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Breast Neoplasms↗
PubMed1992

Breast carcinoma presenting as axillary metastases without evidence of a primary tumor.

BACKGROUND: Sixty cases of axillary metastases from clinically occult breast cancer were analyzed. All cases had histologic evidence of metastatic nodes compatible with breast carcinoma. METHODS: Thirty-three patients underwent breast surgery at the time of histologic diagnosis of the axillary metastases, 6 patients were treated with radiation therapy to the breast, and 17 patients did not receive any immediate treatment of the breast carcinoma (9 of these subsequently had a primary breast carcinoma) during the follow-up. Thirty-seven of 60 patients underwent adjuvant therapy (29 underwent chemotherapy and 8 underwent tamoxifen therapy). From the histologic point of view, the number of metastatic nodes was 1 in 13 patients, 2 to 3 in 10 patients, and 4 or more in 23 patients; the number of metastatic nodes was not evaluable in 14 cases. Invasion was extranodal in 92% of cases. Eighty-six percent of cases were histologically classified as Grade 3 according to Bloom and Richardson. RESULTS: The 5-year and 10-year survival rates were 77% and 58%, respectively. The comparison between the survival curves of the patients treated with immediate surgery/radiation therapy and of the patients whose cases were followed-up without treatment to the breast showed no difference. Adjuvant treatments did not improve prognoses. CONCLUSIONS: The coexistence of a minimal (or unidentifiable) primary carcinoma with an extensive involvement of axillary nodes and a predominance of the undifferentiated histologic type, together with an unexpectedly good prognosis, makes this type of presentation an interesting example of a dissociated host resistance.

Adult↗
PubMed1992

Chemoprevention of breast cancer with retinoids.

Fenretinide [N-(4-hydroxyphenyl)retinamide, 4-HPR] is an effective agent for the inhibition of N-nitroso-N-methylurea-induced breast cancer in rats. This compound has been studied extensively and proved to be safer and less teratogenic than many other retinoids. A major characteristic of 4-HPR is its ability to concentrate in the granular and fat tissue of the breast instead of in the liver. Between January and June 1986, we carried out a phase I study on 101 patients divided into four randomized groups receiving placebo and 100, 200, and 300 mg/day of 4-HPR. Patients received the drug for 6 months without any major toxic effect. This finding was confirmed by another 6-month study in which patients received a common dose of 200 mg/day. In March 1987, a phase III study was started to evaluate the effectiveness of 4-HPR in preventing contralateral primary tumors in women who had already been treated for breast cancer. If 4-HPR succeeds in preventing second primaries in breast cancer patients, it may be useful for a wider group of subjects at high risk for breast cancer. This randomized study was designed with two arms: an intervention group versus a group receiving no treatment. Patients in the intervention group will be treated with 200 mg/day 4-HPR for 5 years. Patients in the control group will not be treated. A further 2 years of follow-up is planned for both groups. Currently, 2450 patients have been recruited. We expect a total accrual of 3500 patients by the end of 1992.

Adult↗
PubMed1991

Narrow excision (1-cm margin). A safe procedure for thin cutaneous melanoma.

We analyzed the results at 8 years of an international, randomized, prospective study carried out by the World Health Organization Melanoma Programme aimed at evaluating the efficacy of 1-cm-margin excision of primary melanomas not thicker than 2 mm. Data for 612 patients were assessable; 305 were randomized to receive 1-cm-margin excision and 307 to receive wide excision (margins of greater than or equal to 3 cm). The major prognostic criteria were similar in the two groups. Breslow thickness was 0.99 mm in the narrow excision group and 1.02 mm in the wide excision group. Disease-free and overall survival rates (mean follow-up period, 90 months) were similar in the two groups. Only four patients had a local recurrence as a first relapse. All underwent narrow excision, and each had primary melanomas thicker than 1 mm.

Adult↗
PubMed1991

Evaluation of resection margins after breast conservative surgery with monoclonal antibodies.

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.

Antibodies, Monoclonal↗
PubMed1991

New developments in breast cancer research.

The last few years have shown an extraordinary development of laboratory and clinical research in breast cancer. The areas which appear particularly important for possible clinical application are many and diversified. In this review we will update the present knowledge regarding four major issues: 1) biologic and molecular tests of prognostic significance in operable breast cancer patients; 2) detection of breast cancer cells in the bone marrow; 3) the endocrine aspects of breast cancer treatment; and 4) the indication of conservative treatments.

Breast Neoplasms↗
PubMed1990

Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more.

In 165 women with breast cancer who were candidates for mastectomy because the largest diameter of the tumor was 3 cm or more, we administered primary chemotherapy in the attempt to substitute conservative for mutilating surgery. We then systematically quantitated tumor reduction by clinical, radiologic, and histopathologic evaluations. Five consecutive groups of 33 patients received cyclophosphamide, methotrexate, and fluorouracil (CMF); fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC); or fluorouracil, epirubicin, and cyclophosphamide (FEC). The regimens for the five groups were as follows: group 1, three cycles of CMF; group 2, four cycles of CMF; group 3, three cycles of FAC; group 4, four cycles of FAC; and group 5, three cycles of FEC. In response to primary chemotherapy, 157 of the 161 assessable patients showed measurable tumor shrinkage; progressive disease was documented in four. Tumor shrinkage to less than 3 cm was documented in 127 (81%) of the 157 women subjected to surgery, thus allowing a breast-saving procedure, rather than modified radical mastectomy, in these 127 women. Histopathologic complete remission was documented in seven patients. Tumor response was unrelated to age, menopausal status, DNA content (ploidy), [3H]thymidine-labeling index, drug combination used, or number of treatment cycles in excess of three. The degree of response was inversely proportional to the initial tumor size, and the frequency of response was greater in receptor-negative tumors. Severe vomiting and hair loss were less frequent with CMF than with anthracycline-containing regimens, and the frequency of severe leukopenia and thrombocytopenia was minimal. Our results challenge the classical indication for primary mastectomy by showing that use of full-dose primary chemotherapy, sequentially combined with conservative surgery and radiation, can offer an effective and safe alternative to women concerned about the preservation of body integrity.

Antineoplastic Combined Chemotherapy Protocols↗