Breast cancer among HIV-infected patients: the experience of the European Institute of Oncology.
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Adult↗
Biomedical subjects
Umberto Veronesi
Publications and source records attributed to Umberto Veronesi.
Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results.
We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5-year follow-up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified.
Adult↗
Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial.
OBJECTIVE: To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SETTING AND PARTICIPANTS: 5408 healthy women who had had hysterectomies, recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy. INTERVENTION: Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years. MAIN OUTCOME MEASURE: Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (> or = 1.5 times upper limit of normal) over a six month period. RESULTS: During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo)--hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to 7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial hypertension (2.0, 1.0 to 3.8). Twenty women had liver biopsies: 15 were diagnosed as having mild to moderate steatohepatitis (12 tamoxifen, 3 placebo), and five had fatty liver alone (1 tamoxifen, 4 placebo). No clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 8.7 years. CONCLUSIONS: Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome, but the disease, in both the tamoxifen and the placebo group, after 10 years of follow up seems to be indolent.
Adult↗
Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial.
BACKGROUND: Tamoxifen, a selective estrogen-receptor modulator, increases venous thromboembolic events (VTE), but the factors explaining this risk are unclear. Atherosclerosis may induce VTE, or the 2 conditions may share common risk factors. We assessed the effect of tamoxifen on VTE in a breast cancer prevention trial and studied its association with risk factors for VTE. METHODS AND RESULTS: The incidence of VTE was studied in 5408 hysterectomized women randomly assigned to tamoxifen 20 mg/d or placebo for 5 years. There were 28 VTEs on placebo and 44 on tamoxifen therapy (hazard ratio [HR]=1.63; 95% confidence interval [CI], 1.02 to 2.63), 80% of which were superficial phlebitis, accounting for all of the excess due to tamoxifen within 18 months from randomization. Compared with placebo, the risk of VTE on tamoxifen was higher in women aged 55 years or older, women with a body mass index > or =25 kg/m2, elevated blood pressure, total cholesterol > or =250 mg/dL, current smoking, and a family history of coronary heart disease (CHD). Of the 685 women with a CHD risk score > or =5 who entered the trial, 1 in the placebo arm and 13 in the tamoxifen arm developed VTE (log-rank P=0.0013). In multivariate regression analysis, age > or =60 years, height > or =165 cm, and diastolic blood pressure > or =90 mm Hg had independent detrimental effects on VTE risk during tamoxifen therapy, whereas transdermal estrogen therapy concomitant with tamoxifen was not associated with any excess of VTE (HR=0.64; 95% CI, 0.23 to 1.82). CONCLUSIONS: Women with conventional risk factors for atherosclerosis have a higher risk of VTE during tamoxifen therapy. This information should be incorporated into counseling women on its risk-benefit ratio, particularly in the prevention setting.
Adult↗
Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution.
BACKGROUND: Reliable predictors of metastatic involvement would enable a better selection of candidate patients for sentinel lymph node biopsy (SLNB) and possibly allow identification of patients with such a low risk of axillary sentinel lymph node (SLN) involvement to be even spared SLNB. METHODS: The authors evaluated 4351 consecutive patients surgically treated for breast carcinoma who also underwent SLNB. Clinicopathologic features significantly associated with SLN metastases by univariate analysis were included in a multivariate model. RESULTS: By multivariate analysis, the prevalence of SLN metastases was associated directly with tumor size, multifocality, and with the occurrence of peritumoral vascular invasion (PVI; all P < 0.0001), and was associated inversely with a favorable histotype (P = 0.0007) and lack of progesterone receptors (P = 0.004). A predictive model based on the features more closely associated with SLN status documented that the patients with a favorable tumor type </= 1 cm in size and without PVI (n = 178 [4% of the population]) had the lowest risk of SLN metastases (9.5%) whereas patients with tumors > 2 cm and with PVI (n = 250 [5.7% of the population]) had the highest risk (77.2%) of SLN involvement. CONCLUSIONS: Tumor size and PVI emerged as the most powerful independent predictors of SLN metastases. Although no combination of features identified patients with a < 9.5% risk of SLN metastases, the current data may be used to tailor the management of patients with breast carcinoma with the aim of minimizing as much as possible the diagnostic and therapeutic procedures, thus improving the quality of life of the patients without any adverse effect on their survival rates.
Adolescent↗
Full-dose intraoperative radiotherapy with electrons in breast surgery: broadening the indications.
HYPOTHESIS: Although postoperative fractionated radiotherapy (PFR) remains the standard method for conservative treatment of breast carcinomas, widespread experience in the use of full-dose intraoperative radiotherapy with electrons (ELIOT) merits its application in novel clinical situations, although long-term results of ongoing clinical trials have not been fully reported. DESIGN: Retrospective case series. SETTING: Division of breast surgery in a comprehensive cancer center. PATIENTS: From June 1999 to September 2003 ELIOT was used as the sole radiotherapy in 355 patients with unifocal invasive carcinoma who were candidates for breast-conserving surgery and most of whom were participating in an ongoing institutional trial. In a group of patients in whom PFR was not considered safe or feasible (because of previous mantle field irradiation for Hodgkin disease, cosmetic breast augmentation, severe cardiopathy, large hypertrophic scarring from skin burns, vitiligo, and geographic or social obstacles), ELIOT was performed outside of the ongoing trial. RESULTS: No particular adverse effects, unusual acute reactions, late sequelae, and local or systemic events were noted in these patients after a mean follow-up of 27.3 months. CONCLUSIONS: In appropriated selected patients, when it is critical to perform PFR after breast-conserving therapy, a single dose of ELIOT may be considered to avoid mastectomy, reduce potential treatment toxicity, improve quality of life, and resolve logistic problems. The long-term results of ongoing clinical trials will further delineate patients in whom ELIOT may replace PFR.
Aged↗
Conservative treatment of breast cancer: its evolution.
BACKGROUND: Over recent decades, breast carcinoma surgery has witnessed a considerable evolution. The extent of surgery undertaken has progressively reduced, leading to less disfigurement and a significant improvement in quality of life, thereby offering women considerable motivation to seek early diagnosis. From an oncological perspective, outcome was found to be equally effective, and this key observation provided us with significant impetus to investigate the effects of reducing the radiotherapy field. PATIENTS AND METHODS: We present the achievements made so far in the conservative treatment of breast carcinoma, based on experiences at the European Institute of Oncology in Milan and, prior to 1994, at the Milan Cancer Institute. RESULTS AND DISCUSSION: Conservative surgery of breast carcinoma, both in the breast and in the axillary nodes, has yielded very good results in terms of overall survival and impact on quality of life. The reduction of the radiation field, conducted in our Institute by means of electron intraoperative radiotherapy (ELIOT), is currently the subject of evaluation via a randomised trial.
Breast Neoplasms↗
The pilot trial on intraoperative radiotherapy with electrons (ELIOT): update on the results.
BACKGROUND: Intraoperative radiotherapy with electrons (ELIOT) is under evaluation in the conservative treatment of breast carcinoma. At the European Institute of Oncology we started our study on ELIOT in 1999; the first step has been a phase I-II trial to test feasibility and tolerance of ELIOT in patients candidate to breast conserving surgery. PATIENTS AND METHODS: From July 1999 to September 2000, 101 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by ELIOT. The trial was based on a dose-escalation starting from 10 Gy: we tested the dose-levels of 10, 15, 17, 19 and 21 Gy. The dose-levels of 10 and 15 Gy were followed by a reduced course of external fractionated radiotherapy. Most patients received 21 Gy intraoperatively. Patients were evaluated 1, 3, 6 and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. RESULTS: After a mean follow-up of 42 months, 16 patients (16%) developed breast fibrosis, mild in 15, severe in one, which resolved within 24 months. Two patients suffered of postoperative infection, and four developed a lyponecrosis in the treated area. CONCLUSION: The first group of patients treated with ELIOT in the phase I-II trial are confirming the good impact of the procedure in terms of tolerance and quality of life.
Aged↗
Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection.
Sentinel node biopsy in patients with breast carcinoma accurately predicts the axillary nodal status. However, in some 6% of patients with negative sentinel nodes the remaining axillary nodes harbour metastases. Our purpose was to observe a large number of patients who did not undergo an axillary dissection after a negative sentinel node biopsy for the appearance of overt axillary metastases. 953 patients treated from 1996 to 2000, with negative sentinel nodes not submitted to axillary dissection, were followed-up to 7 years, with a median follow-up of 38 months. Fifty-five unfavourable events occurred among the 953 patients, 37 (4%) related to the primary breast carcinoma. Three cases of overt axillary metastases were found: they received total axillary dissection and are presently alive and well. The 5 year overall survival rate of the whole series was 98%. Patients with negative sentinel node biopsies not submitted to axillary dissection show during follow-up a rate of overt axillary metastases that is lower than that expected.
Adult↗
Chemoprevention: from research to clinical oncology.
Chemoprevention is by now an emerging area of clinical oncology addressed to healthy individuals at higher risk for cancer, subjects with precancerous conditions, and patients who are at risk for a second primary cancer. The important results of large trials with various agents and the more accurate methods of risk assessment have already had implications in clinical practice. Recently, a number of compounds have shown to be clinically effective at various organ levels, often covering all the three settings of primary, secondary and tertiary prevention. There is proof today that at least 3 of the 4 'big killers' in oncology--breast, colon and prostate cancer--and oral cancer are to a certain extent preventable by chemopreventive drugs. The missing piece so far is lung cancer. The expanding molecular drug development is providing the tools for a more effective and safer molecular-targeted prevention. Combination chemoprevention and the use of agents with multiple effects are other particularly promising chemoprevention strategies.
Anticarcinogenic Agents↗
Intraoperative electrons.
Intraoperative radiotherapy (IORT) has been used for many years for treating patients with various locally-advanced malignancies, usually combined with external-beam radiation therapy (EBRT). Long-term results confirm that IORT improves local control, which is generally associated with increased survival. Recently, electron-beam IORT has been used as the sole treatment for patients with earlier-stage cancers, especially for breast tumors, with extremely promising results. Most of this work has been done at the European Institute of Oncology in Milan. We report the rationale and techniques of the use of electron intraoperative treatment (ELIOT) and the results of our different clinical studies. In our opinion, ELIOT may be an excellent alternative to EBRT for the treatment of patients with early-stage breast cancer. However, intensive long-term follow-up is needed to fully evaluate local control and possible side effects.
Beta Particles↗
Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery: experience with 590 cases.
BACKGROUND: Previous studies show that local recurrences after breast-conserving treatment occur in the site of the primary tumor. The need for postoperative radiotherapy on the whole breast is challenged in favor of radiotherapy limited to the area of the breast at high risk of recurrence. The new mobile linear accelerators easily moved close to the operating table to allow the full-dose irradiation during surgery. PATIENTS AND METHODS: From July 1999 to December 2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by intraoperative radiotherapy with electrons (ELIOT). Most patients received 21 Gy intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. RESULTS: After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19 patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which resolved within 24 months. Three patients (0.5%) developed local recurrences, 3 patients ipsilateral carcinomas in other quadrants and other 5 patients contralateral breast carcinoma. One patient (0.2%) died of distant metastases. CONCLUSIONS: ELIOT is a safe method for treating conservatively operated breasts, avoids the long period of postoperative radiotherapy, and reduces drastically the cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs. Results on short-term and middle-term toxicity up to 5 years of follow-up are good. Data on local control are encouraging.
Adenocarcinoma↗
The 6th Milan Breast Cancer Conference, Milan, Italy, 16-18 June 2004.
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Breast Neoplasms↗
Clinicopathologic characteristics of 143 patients with synchronous bilateral invasive breast carcinomas treated in a single institution.
BACKGROUND: Synchronous bilateral invasive breast carcinoma (SBIBC) ranged in incidence from 0.3% to as high as 12%. METHODS: Between April 1997 and February 2003, 143 consecutive patients with SBIBC were treated at the European Institute of Oncology (Milan, Italy). Their information was collected prospectively in a database. The bilateral tumors were divded into left and right tumors. Tumor size, histology, grade, lymph node status, estrogen (ER) and progesterone receptor (PgR) status, HER-2 expression, peritumoral vascular invasion (PVI), Ki-67 expression, extensive in situ component (EIC), and multifocality between the two groups were analyzed. During the same time period, 6218 patients with unilateral invasive breast carcinoma (UIBC) were analyzed in the same manner for comparison with the patients with SBIBC. RESULTS: There were no significant differences between left and right tumors, and the observed histopathologic agreement within the same patient was significantly superior than statistically expected for all characteristics except size, lymph node status, and multifocality. When compared with patients with UIBC, patients with SBIBC were more likely to present with smaller tumors and showed a higher frequency of invasive lobular carcinoma, lower histologic grade, higher rate of ER and PgR positivity, and lower PVI and Ki-67 expression. CONCLUSIONS: The high concordance of histopathologic characteristics between SBIBC within the same patient could reflect a particular hormonal environment that influenced either the initiation and development of these lesions simultaneously and independently from the single or multi-clonal origin, either a less aggressive biological behavior compared with UIBC. In particular, the strong agreement of the observed EIC in SBIBC within the same patient seemed to definitively exclude the metastatic origin of these tumors.
Adenocarcinoma, Mucinous↗
Re: Trends in the treatment of ductal carcinoma in situ of the breast.
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Breast Neoplasms↗
Sentinel node biopsy in elderly breast cancer patients.
INTRODUCTION: Even if an increasing body of data suggests that sentinel node biopsy is a safe and accurate method of screening the axillary nodes for metastasis, there is a tendency to perform less extensive or no axillary surgery in older breast cancer women. The aim of this study therefore was to assess the safety of the procedure as well as the rate of axillary recurrences after sentinel node biopsy in this older population. METHODS: Between May 1997 and March 2003, 241 consecutive elderly patients (>or=70 years) with operable breast cancer up to 3 cm and clinically negative axillary lymph nodes were entered into this study. Sentinel node was identified using 5-10 MBq of 99 mTc-labeled colloidal particles and examined with immediate complete intraoperative frozen-section. RESULTS: The sentinel node identification rate was 100%. Ninety-seven percent of the patients underwent breast-conserving surgery. In 90 out of 241 patients (37.3%) the sentinel node was positive for metastasis and complete axillary dissection was immediately performed. In 56.7% of these patients the sentinel node was the only lymph node involved. Micrometastasis in the sentinel node was detected in 30 of the 90 (33.3%) patients. A total of 151 patients (62.7%) were sentinel node negative and no further surgical treatment was done. There were no axillary recurrences at a median followup of 29.7 months (range 3-87 months). The overall survival of this group of patients was 97.9%. CONCLUSIONS: Sentinel node biopsy is a safe and accurate method of screening the axillary nodes for elderly women with operable breast cancer less than 3 cm. The absence of axillary recurrences after sentinel node biopsy without complete axillary dissection supports the hypothesis.
Age Factors↗
Intraoperative radiotherapy: the debate continues.
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Breast Neoplasms↗
Male breast cancer: a special therapeutic problem. Anything new? (Review).
Carcinoma of the male breast (MBC) is an uncommon phenomenon, accounting for <1% of all malignancies in man. It represents a biologically heterogeneous disorder, and its clinical course may vary from indolent and slowly progressive to rapidly metastatic disease. Most of our current knowledge regarding its biology, natural history, and treatment strategies has been extrapolated from its female counterpart. Information regarding prognostic relevance of new molecular markers is limited. At the European Institute of Oncology we performed a study showing data in which p21Waf1 and p27Kip1 proteins were evaluated in a series of male breast cancer patients. Our data suggest that the immunohistochemical evaluation of p21Waf1 and p27Kip1 expression in male breast carcinomas may be a further useful marker for selecting patients who express functional proteins that can be predictive for the most efficient endocrine response. Moreover, searching for more conservative treatment, we introduced in our clinical practice sentinel node biopsy, and if present, sentinel node biopsy of the internal mammary chain. The potential clinical implications of complete nodal staging are far-reaching, and give us a major new opportunity to stratify male patients with breast cancer for appropriate surgery as well as giving valuable prognostic information. Male breast cancer has biological differences compared with female breast cancer. It responds to hormonal manipulation and chemotherapy, but optimal treatment regimens in males are unknown. By analogy to the female breast cancer, post-mastectomy radiotherapy should be proposed in case of advanced T stage and/or lymph node positivity (considering the small volume of the male mammary gland, we suggest post-mastectomy irradiation in case of T >1 cm and/or presence of >1 metastatic axillary lymph node). Breast conserving surgery, performed in selected cases of male breast cancer, should be always followed by radiotherapy. Despite a wealth of small retrospective studies on MBC, its rarity means there is a lack of prospective randomized controlled treatment trials, which needs to be addressed if significant advances are to be made in the treatment of this unusual challenging disease.
Breast Neoplasms, Male↗