PubMed Health⌕ Search

Biomedical subjects

Umberto Veronesi

Publications and source records attributed to Umberto Veronesi.

At least 19 recordsLinked to original sources

Breast conservation: current results and future perspectives at the European Institute of Oncology.

In the recent 10 years breast cancer treatments' scenario is radically changed. Extraordinary new surgical approaches give more and more conservative solutions both for the breast and especially for the axilla avoiding dissection in more than 80% of early cases. Instrumental early diagnosis and clinical prediction are now able to identify very initial cases often in premalignant stage. Technology arrived in the operating theatre for the intraoperative radiotherapy treatments giving to the patients the better quality of life with the help also of the plastic surgeons. There are still near horizons to reach: modern neo-adjuvant and adjuvant treatments are going quickly from the laboratory to patient's bed.

Breast Neoplasms↗

IART: intraoperative avidination for radionuclide treatment. A new way of partial breast irradiation.

A new procedure, known as Intraoperative Avidination for Radionuclide Therapy (IART), is described in breast cancer patients. In this paper, we provide proof of the principle that intraoperative injection of avidin in the tumour bed after quadrantectomy allows homing in of intravenously (IV) administered radioactive biotin to the target site. This approach of targeted therapy consists of two steps: (i) "avidination" of the anatomical area of the tumour with avidin injected by the surgeon, into and around the tumour bed; (ii) targeting the anatomical area of the tumour by IV injection of radiolabelled biotin. The scintigraphic images demonstrated fast and stable uptake of labelled biotin at the site of operated breast. The radiation dose released to the index quadrant was more than 5 Gy/GBq, consistent with a boost of 20 Gy for an activity of 3.7 GBq 90Y-biotin (100mCi). A further large clinical trial facing IART in combination with reduced external-beam radiotherapy is, in our opinion, fully justified.

Adult↗

Ipsilateral breast tumor reappearance in patients treated with conservative surgery after primary chemotherapy. The role of surgical margins on outcome.

BACKGROUND AND OBJECTIVES: To evaluate the ipsilateral breast tumor reappearance (IBTR) rate after breast conservative surgery (BCS) following primary chemotherapy (PC) and to assess whether positive margins affects IBTR rate and overall survival (OS). METHODS: Three hundred nine women candidates for mastectomy received PC before surgery. One hundred ninety-five patients (63.1%) underwent BCS and 114 patients (36.9%) a modified radical mastectomy. RESULTS: After a median follow-up of 41 months (range 7-90), 13 patients of the 195 treated with BCS had an IBTR (6.7%), 6 patients had a regional relapse (3.1%), 28 women had distant metastases (14.4%). Twenty-three patients died of breast cancer (11.8%). Twenty-four patients treated with BCS had positive margins (12.3%). At 3 years, the crude cumulative incidence of local recurrence was 4.7% in women with negative margins, and 13.3% in women with positive margins (P=0.05). Cumulative incidence of distant metastases was similar in patients with positive and negative margins (P=0.16) and there was no significant difference in terms of OS according to the margin status (P=0.577). CONCLUSIONS: BCS after PC has an acceptable rate of IBTR. After a short follow-up, the presence of positive margins does not affect OS.

Adult↗

Linking survival of HER2-positive breast carcinoma patients with surgical invasiveness.

The early peak of relapse in patients with breast carcinomas that overexpress HER2 oncoprotein and dissemination to the axillary lymph nodes might be related to proliferation of micrometastatic lesions induced by EGF family growth factors released at the time of surgery. If the levels of these growth factors have an impact on relapse, the survival of patients with positive nodes and HER2-positive tumours should be dependent on surgery wideness. To test this hypothesis, HER2 status of primary tumours from patients included in a randomized clinical trial addressing conservative quadrantectomy versus radical mastectomy was retrospectively analyzed. In HER2-negative patients, independently of node infiltration, and in HER2-positive patients without node infiltration, no differences in survival according to the type of surgery were observed. In patients with positive nodes and HER2-positive tumours the estimation of the time-dependent log-hazard ratios showed that radical mastectomy significantly increased early death rates (P=0.037).

Adult↗

Rethinking TNM: breast cancer TNM classification for treatment decision-making and research.

Current classification for solid tumors is based upon characteristics of their extent. Size of the primary tumor, presence of metastatic regional lymph nodes and/or of distant metastases are the key elements for their categorization. Treatment decision-making may depend upon defined extent of disease, but it requires the knowledge of several other factors. Furthermore, effective therapeutics is less dependent upon extent of disease, biological features being increasingly instrumental for treatment choice. A new classification that integrates both requisites is proposed. The scope of this proposal is to transform the current rigid and gross categorization into a more analytical and fine tuned listing including biological variables, making staging allocation more flexible and functional for proper clinical and research needs in the present and for the future. The significant changes we propose are:

Breast Neoplasms↗

Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study.

BACKGROUND: In women with breast cancer, sentinel-lymph-node biopsy (SLNB) provides information that allows surgeons to avoid axillary-lymph-node dissection (ALND) if the SLN does not have metastasis, and has a favourable effect on quality of life. Results of our previous trial showed that SLNB accurately screens the ALN for metastasis in breast cancers of diameter 2 mm or less. We aimed to update this trial with results from longer follow-up. METHODS: Women with breast tumours of diameter 2 cm or less were randomly assigned after breast-conserving surgery either to SLNB and total ALND (ALND group), or to SLNB followed by ALND only if the SLN was involved (SLN group). Analysis was restricted to patients whose tumour characteristics met eligibility criteria after treatment. The main endpoints were the number of axillary metastases in women in the SLN group with negative SLNs, staging power of SLNB, and disease-free and overall survival. FINDINGS: Of the 257 patients in the ALND group, 83 (32%) had a positive SLN and 174 (68%) had a negative SLN; eight of those with negative SLNs were found to have false-negative SLNs. Of the 259 patients in the SLN group, 92 (36%) had a positive SLN, and 167 (65%) had a negative SLN. One case of overt clinical axillary metastasis was seen in the follow-up of the 167 women in the SLN group who did not receive ALND (ie, one false-negative). After a median follow-up of 79 months (range 15-97), 34 events associated with breast cancer occurred: 18 in the ALND group, and 16 in the SLN group (log-rank p=0.6). The overall 5-year survival of all patients was 96.4% (95% CI 94.1-98.7) in the ALND group and 98.4% (96.9-100) in the SLN group (log-rank p=0.1). INTERPRETATION: SLNB can allow total ALND to be avoided in patients with negative SLNs, while reducing postoperative morbidity and the costs of hospital stay. The finding that only one overt axillary metastasis occurred during follow-up of patients who did not receive ALND (whereas eight cases were expected) could be explained by various hypotheses, including those from cancer-stem-cell research.

Adult↗

Atypia and Ki-67 expression from ductal lavage in women at different risk for breast cancer.

PURPOSE: Ductal lavage provides adequate material and detects atypical cells from ducts in women at increased risk of breast cancer, but the clinical significance of this finding is unclear. We studied the prevalence and predictors of atypia in addition to the proliferation-associated antigen Ki-67 expression in ductal lavage done in women at different risk of breast cancer. RESULTS: Ductal lavage was attempted in 202 women at increased risk and in 16 at average risk. Lavage could not be done in 20 women at increased risk because of anatomic impediments. Seven average-risk women (44%) had samples with inadequate cytology versus 30 women at higher risk (16%; P = 0.014). Atypia was observed in two average-risk women [22%; 95% confidence interval (95% CI), 3-60%]. The prevalence of atypia was 33% in women with a 5-year risk of > or =1.3% according to the Gail model (25 of 75; 95% CI, 23-45%), 36% in women with an increased probability of or ascertained BRCA mutation (9 of 25; 95% CI, 18-57%), and 52% in women with contralateral breast cancer (27 of 52; 95% CI, 38-66%). Ki-67 expression measured in a consecutive series of 80 women at increased risk was higher in atypical samples (P = 0.0001) and was positively associated with total cell count per slide (P = 0.002). CONCLUSIONS: Atypia is frequent in women at increased risk of breast cancer but it can also be found in average-risk women. Ki-67 expression is associated with atypia and cell yield and it might be assessed as a surrogate biomarker in early-phase chemoprevention trials.

Body Fluids↗

Real-time in vivo dosimetry using micro-MOSFET detectors during intraoperative electron beam radiation therapy in early-stage breast cancer.

PURPOSE: In a previous paper we reported the results of off-line in vivo measurements using radiochromic films in IOERT. In the present study, a further step was made, aiming at the improvement of the effectiveness of in vivo dosimetry, based on a real-time check of the dose. MATERIALS AND METHODS: Entrance dose was determined using micro-MOSFET detectors placed inside a thin, sterile, transparent catheter. The epoxy side of the detector was faced towards the beam to minimize the anisotropy. Each detector was plugged into a bias supply (standard sensitivity) and calibrated at 5 Gy using 6 MeV electrons produced by a conventional linac. Detectors were characterized in terms of linearity, precision and dose per pulse dependence. No energy and temperature dependence was found. The sensitivity change of detectors was about 1% per 20 Gy accumulated dose. Correction factors to convert surface to entrance dose were determined for each combination of energy and applicator. From November 2004 to May 2005, in vivo dosimetry was performed on 45 patients affected by early-stage breast cancer, who underwent IOERT to the tumour bed. IOERT was delivered using electrons (4-10 MeV) at high dose per pulse, produced by either a Novac7 or a Liac mobile linac. RESULTS: The mean ratio between measured and expected dose was 1.006+/-0.035 (1 SD), in the range 0.92-1.1. The procedure uncertainty was 3.6%. Micro-MOSFETs appeared suitable for in vivo dosimetry in IOERT, although some unfavourable aspects, like the limited lifetime and the anisotropy with no build-up, were found. Prospectively, a real-time action level (+/-6%) on dose discrepancy was defined. CONCLUSIONS: Excellent agreement between measured and expected doses was found. Real-time in vivo dosimetry appeared feasible, reliable and more effective than the method previously published.

Breast Neoplasms↗

Nipple-sparing mastectomy in association with intra operative radiotherapy (ELIOT): A new type of mastectomy for breast cancer treatment.

BACKGROUND: Breast-conserving surgery has become the standard approach for about 80% of patients treated for primary breast cancer in most centres. However, mastectomy is still required in case of multicentric and/or large tumours or where recurrences occur after conservative treatment. When a total mastectomy is performed, the removal of the nipple areola complex (NAC) is a strongly debated issue. In fact, although removal of the NAC greatly increases the patient's sensation of mutilation, and the risk of tumor involvement of the areola is reported as a very variable percentage, NAC excision still remains the standard treatment. PATIENTS AND METHODS: From March 2002 to September 2003, 106 nipple sparing mastectomies (NSM) were peformed in 102 patients, 63% of whom had invasive carcinoma and 37% of whom had in situ carcinoma. Four patients underwent bilateral surgery. In all cases, a large or multicentric tumour and/or diffuse microcalcifications, clinically distant from the NAC, were present. During surgery, the tissue under the areola was routinely sampled to exclude the presence of tumor. If disease-free at the frozen sections, the NAC was spared and a NSM was performed. Additionally, a total dose of 16 Gy of radiotherapy (ELIOT) was delivered intraoperatively in the region of the NAC. All the patients underwent an immediate plastic breast reconstruction. RESULTS: In eleven patients (10.4%), the breast tissue under the areola resulted infiltrated at the definitive histological examination: in 10 cases a single or multiple foci of in situ carcinoma and in one case an invasive component were present. Eleven patients (10.4%) developed a superficial skin areolar slough followed by spontaneous healing, and 5 patients (4.7%) lost their NAC due to total necrosis. Among these, one patient had a poor cosmetic result on the NAC with asymmetrical location and required further surgical removal and reconstruction with tattoo and local flap in a better position. When rating the results from 0 (bad) to 10 (excellent), on average, the colour of the areola was rated 9/10, the sensitivity of nipple 3/10, the overall aesthetic result was rated 8/10 by both the surgeon and the patients. Early radiodystrophy (pigmentation) was observed in eight cases (7.5%). After an average follow up of 13 months, one local recurrence, located under the clavicula, far from the NAC, was observed. The preliminary results of the psychological study show a very high satisfaction with the preservation of the nipple (97.6 %), with younger women expressing a higher satisfaction than older counterparts. CONCLUSIONS: In selected cases, NSM with ELIOT of NAC has so far permitted good local control of the disease and satisfactory cosmetic results. Wider surgical experience is required to minimise the risk of leaving tumor cells in the region of the spared NAC and a longer follow up is necessary to evaluate the long term tumor recurrence rate at the NAC.

Breast Neoplasms↗

Second biopsy of axillary sentinel lymph node for reappearing breast cancer after previous sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. METHODS: Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. RESULTS: In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. CONCLUSIONS: Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.

Adult↗

A new option for early breast cancer patients previously irradiated for Hodgkin's disease: intraoperative radiotherapy with electrons (ELIOT).

INTRODUCTION: Patients who have undergone mantle radiotherapy for Hodgkin's disease (HD) are at increased risk of developing breast cancer. In such patients, breast conserving surgery (BCS) followed by breast irradiation is generally considered contraindicated owing to the high cumulative radiation dose. Mastectomy is therefore recommended as the first option treatment in these women. METHODS: Six patients affected by early breast cancer previously treated with mantle radiation for HD underwent BCS associated with full-dose intraoperative radiotherapy with electrons (ELIOT). RESULTS: A total dose of 21 Gy (prescribed at 90% isodose) in five cases and 17 Gy (at 100% isodose) in one case were delivered directly to the mammary gland without acute complications and with good cosmetic results. After an average of 30.8 months of follow up, no late sequelae were observed and the patients are free of disease. CONCLUSION: In patients previously irradiated for HD, ELIOT can avoid repeat irradiation of the whole breast, permit BCS and decrease the number of avoidable mastectomies.

Combined Modality Therapy↗