A. Luini

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

BACKGROUNDnIn 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.nnnMETHODSnWomen 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.nnnFINDINGSnOf 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).nnnINTERPRETATIONnSLNB 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.

Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons

Intraoperative radiotherapy with electrons (ELIOT) after conservative surgery for breast carcinoma was introduced at the IEO in 1999 as a research programme. The results on 1,822 patients treated from January 2000 to December 2008 are reported. Women with unicentric primary breast carcinoma of less than 2.5xa0cm in the largest diameter were assessed by imaging. All patients were treated with breast-conserving surgery (quadrantectomy). ELIOT was delivered by two mobile linear accelerators immediately after breast resection with a single dose of 21xa0Gy. Local side effects of ELIOT were mainly liponecrosis (4.2%) and fibrosis (1.8%). After a mean follow-up of 36.1xa0months, 42 women (2.3%) developed a local recurrence, 24 (1.3%) a new primary ipsilateral carcinomas and 26 (1.4%) distant metastases as first event. Forty-six women died (2.5%), 28 for breast carcinoma and 18 for other causes. Five- and ten-year survivals were, respectively, 97.4 and 89.7%. ELIOT appears a promising feature in early breast cancer treated with breast conserving surgery, reducing the exposure of normal tissues to radiations and shortening the radiation course from 6xa0weeks to one single session.

Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer

BACKGROUNDnThere is limited knowledge about prognosis of selected breast cancer subtypes among very young women.nnnPATIENTS AND METHODSnWe explored patterns of recurrence by age according to four immunohistochemically defined tumor subtypes: Luminal A and Luminal B (estrogen receptor positive and/or progesterone receptor positive and either human epidermal growth factor receptor 2 (HER2) positive and/or high Ki-67), HER2-positive (and) endocrine receptor absent and Triple Negative, in 2970 premenopausal patients with pT1-3, pN0-3 and M0 breast cancer.nnnRESULTSnPatients <35 years of age (315, 11%) presented a significantly increased risk of recurrence and death [hazards ratio (HR) = 1.65, 95% confidence interval (CI) 1.30-2.10 and HR = 1.78, 95% CI 1.12-2.85, respectively] when compared with older patients (2655, 89%) with similar characteristics of disease. This was true considering patients with Luminal B [HR = 1.62, 95% CI 1.21-2.18 for disease-free survival (DFS) and HR = 2.09, 95% CI 0.96-4.53 for overall survival (OS)] and with Triple Negative (HR = 2.04, 95% CI 1.11-3.72 for DFS and HR = 2.20, 95% CI 1.10-4.41 for OS) breast cancer, observing the highest risk of recurrence in the younger patients with HER2-positive breast cancer (HR = 2.37, 95% CI 1.12-5.02) when compared with older patients.nnnCONCLUSIONSnVery young patients with Triple Negative, Luminal B or HER2-positive breast cancer have a worse prognosis when compared with older patients with similar characteristics of disease.

Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: the experience of the European Institute of Oncology and review of the literature.

BackgroundMetaplastic carcinoma of the breast is a rare form of breast cancer and has an uncertain prognostic significance. The purpose of the present study was to compare the clinical course, and prognosis, between this type of tumor and poorly differentiated ductal carcinoma.Patients and methodsWe analyzed 37 cases of metaplastic carcinoma of the breast treated at our institution (European Institute of Oncology in Milan, Italy) between 1997 and 2004, comparing them with 72 cases (control group) of poorly differentiated ductal carcinoma. All 109 patients had negative receptors and were G3 at final histology. The control cases were matched according to year of surgery, pT (pT1 vs. pT2/3/4), and pN (absent vs. present).ResultsOf the 37 patients, eleven died from disease progression, eight developed metastatic disease and two experienced local recurrence. In the control group (72 patients) we observed three deaths due to disease progression, 13 distant metastases, and two local recurrences.ConclusionThe overall survival in the metaplastic carcinoma group was significantly worse than in the control group. As regards to disease-free survival, there was no statistically significant difference between the two groups.

Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer.

Local recurrences after breast-conserving surgery occur mostly in the quadrant harbouring primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area while irradiation of the whole breast may be avoided. We have developed a new technique of intraoperative radiotherapy of a breast quadrant after the removal of the primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Different dose levels were tested from 10 to 21 Gy without important side effects. A randomized trial is currently ongoing in order to compare conventional irradiation and ELIOT. More than 400 patients have been enrolled. In addition a new approach for nipple and areola complex conservation, including ELIOT, is under investigation.

The value of radiotherapy on metastatic internal mammary nodes in breast cancer. Results on a large series

The regional nodal mapping, is a fundamental step to stage breast carcinoma. In addition to the axillary nodes status, the involvement of internal mammary nodes is an important prognostic factor. Six hundred and sixty-three patients with breast carcinoma, mainly in the inner quadrants, underwent a biopsy of internal mammary nodes. Positive internal mammary nodes were found in 68 out of 663 cases (10.3%) representing 27.2% of all cases with regional node metastases (250). When histologically proven metastases were detected, radiotherapy was administered to the internal mammary nodes chain. In 254 cases, the surgeons exploration was guided by a gamma probe. Out of these cases, 28 (11.0%) showed metastatic involvement. Out of the other 409 cases, not radioguided, 40 showed positive nodes (9.8%). Patients with internal mammary metastases treated with radiotherapy and appropriate systemic treatment showed an excellent survival (95% at 5 years), a result which is in opposition to the previous experience, which stated that invasion of internal mammary nodes is an ominous prognostic sign. We assume that this excellent result is due to radiotherapy to internal mammary nodes and we propose that exploration of internal mammary nodes should be part of the staging process of carcinomas of the medial part of the breast.

The surgical margin status after breast-conserving surgery: discussion of an open issue

Hypothesis The best therapeutic approach to the involved or proximal surgical margins has not been defined yet; surgical margins status can influence the local relapse of disease in breast carcinoma, but the impact on overall survival has not been clearly demonstrated. Purpose of this work is to find in the available literature further evidence to guide the therapeutic behaviour in patients with close margins by invasive carcinoma. Design Review of the currently available literature on the evaluation of surgical margins in breast conserving surgery; influence of margin involvement by invasive component or intraductal component. Patients or other participants Literature research by PubMed on the topics of breast carcinoma, conservative surgery and margin definition and status; therapeutic approach to involved margins. Main outcome measure We reviewed the available literature focusing our attention to the definition of clear surgical margins and to the value of the close proximity of margins in relation to the local control of disease and the best therapeutic management of different situations. Results Further evidence is needed on large numbers of patients to understand how to evaluate surgical margins in invasive breast carcinoma. Conclusions There is no consensus on the definition of “clear surgical margins”, and the ideal approach to the close proximity of margins has not been defined. It is not sure whether a new surgical procedure is really needed in every case of close proximity of tumor cells to the margins. Radiation therapy could be a good option in the management of these cases, but further evidence is needed to establish the real impact of clear surgical margins on local control of disease and, furthermore, on survival.

Paget’s disease of the breast: the experience of the European institute of oncology and review of the literature

Background Paget’s disease of the breast is an uncommon presentation of breast malignancy, accounting for 1–3% of all the breast tumors and presents in different histopathologic patterns: in association with an underlying invasive or non invasive carcinoma, or without any underlying neoplasia. In the literature, different methods are used for the treatment. Mastectomy with or without axillary dissection has been considered as the standard treatment procedure for many years. Several studies have already shown that breast conservation with radiation therapy is an oncologically safe option. Regarding the axillary approach, several studies have documented the presence of positive sentinel lymph node even in Paget’s disease alone. The objective of this study was to retrospectively analyze outcome of patients affected by Paget’s breast disease and to define our institutional experience. Patients and methods Between May 1996 and February 2003, 114 patients with confirmed Paget’s disease of the breast were retrieved and underwent surgery at the European Institute of Oncology of Milan, Italy. The median age of the patients was 54xa0years at the time of the diagnosis. In our study, the histopathological examination of the operated specimen revealed one hundred seven patients with Paget’s disease associated with an underlying invasive or non invasive carcinoma, and seven patients without underlying carcinoma. Patients underwent either conservative breast surgery or mastectomy, with or without sentinel lymph node biopsy and/or axillary surgery. Each patient was evaluated after surgery at a multidisciplinary meeting to selecting systemic therapy. Results Seven patients had “pure” Paget’s disease of the breast and one hundred seven had the disease associated with an underlying carcinoma. As surgical techniques 71 mastectomies and 43 breast conserving surgeries have been performed. Complete axillary dissection was done in patients with clinically positive lymph node and/or sentinel lymph node biopsy positive. Sentinel lymph node biopsy was performed in nineteen patients with invasive component and five were positive and underwent axillary dissection. Eleven sentinel lymph node biopsies were done in patients with non invasive component and none of them was positive. Adjuvant systemic therapies were based on the final tumor, node and metastasis stage: thirty patients received adjuvant chemotherapy alone, fourteen received endocrine treatment alone, twenty-six patients were evaluated to receive both chemo and endocrine therapy. The median duration of follow up was 73xa0months and was updated in the last 6xa0months. Five patients developed local recurrence, one had regional recurrence, another two had loco-regional recurrences and fourteen had distant metastasis as a first event. Malignancy-related deaths were censored in the statistical analyses cancer for and due to another tumor in eleven patients. Additionally, deaths were not related to malignancy totally in thirteen patients. Conclusions Screening examination and imaging techniques are fundamental. Breast conserving surgery combined with breast irradiation for patients with invasive and non invasive breast carcinoma has become the treatment of first choice. All surgical conservative approaches should include the complete nipple–areolar complex and margins of resected specimen free of tumor. Thanks to the evolution of the conservative approach, good cosmetic result can be obtained. To be informed about the axillary lymph node status and to avoid the patient to have a second surgical approach, sentinel lymph node biopsy should be performed.

The pilot trial on intraoperative radiotherapy with electrons (ELIOT): Update on the results

SummaryBackground: 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 2.5xa0cm received wide resection of the breast followed by ELIOT. The trial was based on a dose-escalation starting from 10xa0Gy: we tested the dose-levels of 10, 15, 17, 19 and 21xa0Gy. The dose-levels of 10 and 15xa0Gy were followed by a reduced course of external fractionated radiotherapy. Most patients received 21xa0Gy intraoperatively. Patients were evaluated 1, 3, 6 and 12xa0months after surgery, and thereafter every 6xa0months, to look for early, intermediate, late complications, and other events.Results. After a mean follow-up of 42xa0months, 16 patients (16%) developed breast fibrosis, mild in 15, severe in one, which resolved within 24xa0months. 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.

Radiation protection in radioguided surgery of breast cancer

The protocols for sentinel lymph node biopsy and radioguided occult lesion localization could potentially be of great value in the management of breast cancer patients. Both involve the injection of a 99Tcm-labelled radiopharmaceutical close to or into the lesion, localization of the sentinel lymph node or occult lesion by scintigraphy, and surgical removal with the aid of a hand-held gamma-ray detector. We present dosimetric data on patients and hospital personnel involved in these procedures. For evaluation of radiation protection, we measured the absorbed dose and air kerma rate. Activity levels in excised tissues and surgical instruments were also determined. For patients, the mean absorbed dose to the abdomen was 0.45 mGy, which is low compared to doses received from other diagnostic examinations. For surgeons after 100 operations, the mean absorbed dose to the hands was 0.45 mGy and the mean effective dose 0.09 mSv. Absorbed doses to all hospital personnel involved in the procedures were very low compared to recommended annual limits stipulated by the International Commission on Radiological Protection. We conclude that these procedures, performed according to protocols laid down by the European Institute of Oncology, Milan, are safe from the point of view of radiological protection and that only routine precautions are necessary.