Early invasive cancer and partial intraoperative electron radiation therapy of the breast: experience of the jules bordet institute.

Objectives. The aim of this prospective phase II study is to evaluate the treatment of early-stage breast cancer (T1 N0) with intraoperative electron radiation therapy (IOERT) in terms of local control, early complications, and cosmesis. Patients and Methods. From February 2010 to February 2012, 200 patients underwent partial IOERT of the breast. Inclusion criteria were unifocal invasive ductal carcinoma, age ≥40 years, histological tumour size ≤20 mm, and no lymph node involvement. A 21 Gy dose was prescribed over the 90% isodose line in the tumour bed. Median follow-up is 23.3 months (7-37). Results. Acute toxicity was not frequent (Grade 1: 4.5%, Grade 2: 1%). The cosmetic result was considered to be very good or good in 92.5%. One ipsi lateral out-quadrant recurrence at 18 months was observed. The crude and actuarial local recurrence rates after median follow-up were 0.5% and 0.9%, respectively. Conclusion. The preoperative diagnostic work-up must be comprehensive and the selection process must be rigorous for this therapeutic approach reserved for small ductal unifocal cancers. After a 23.3-month median follow-up time, the clinical results of IOERT for selected patients are encouraging for the locoregional recurrence and the toxicity rates. The satisfaction of our patients in terms of quality of life was extremely high.

Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes.

BACKGROUND: In breast cancer patients, the status of the sentinel lymph nodes (SLNs) has been shown to accurately reflect the presence of metastases in the axillary lymph nodes (ALNs). Intra-operative SLN evaluation by frozen section histology may miss positive cases, leading to a second surgery for complete ALN dissection. Permanent section histology itself has tissue sampling limitations and is partially dependent on pathologist expertise. METHODS: A prospective study (N=78) was conducted in our institution to validate a new intra-operative molecular assay, the GeneSearch breast lymph node (BLN) assay. This assay quantifies the expression of mammaglobin and cytokeratin-19 genes using quantitative RT-PCR technology to determine SLN status. Fresh SLN sections (2 mm thick) were analyzed alternatively by BLN assay or post-operative histology (haematoxylin-eosin and immunohistochemistry). The subject was considered positive when histology revealed a focus >0.2 mm. RESULTS: BLN assay results corroborated with histologic results in 75 out of 78 patients for an overall agreement of 96%, a sensitivity of 92%, and a specificity of 97%. The positive and negative predictive values of the BLN assay were of 86% (12/14) and 98% (63/64), respectively. Interestingly, a statistically significant correlation was observed between the metastases' histologic size and both assay markers' expression levels as represented by cycle time to positivity (rho > or = 0.71, all p<0.0001). CONCLUSIONS: The performance of the BLN assay in identifying nodal metastases >0.2 mm was similar to that of permanent section histology, with the added advantages of an objective and rapid output that could be used for intra-operative decision to remove additional ALN.

Isotope labelling and axillary node harvesting strategies for breast cancer.

AIMS: The objective of this study was to assess the value of superficial (intradermal) and paratumoral (above the tumor) (ID) injection of labeled colloids for imaging sentinel lymph nodes (SLN) as a rescue technique in breast cancer patients for whom deep (intraparenchymatous) and peritumoral (around the tumor) (IP) injections had failed. METHODS: We assessed data from 2 groups of women: 469 women for whom IP injections successfully visualized a SLN (IP-only) and 52 women for whom IP injections were unsuccessful and ID injection was performed (IP0-ID). Patient characteristics and SLN results were compared. RESULTS: Most characteristics of the two patients series were similar. However, IP0-ID patients were on average 10years older than the IP-only patients and had more grade-III tumors. The false negative rate (FNR) for the IP0-ID patients (9/25, 23.8%) was significantly higher than for the IP-only patients (12/240, 5%; p<0.01) and for a subgroup of IP-only patients older than 50 years (8/159, 5%; p=0.009). Four of five false negatives in the IP0-ID group involved a tumor in the outer quadrants. The FNR for cases with external tumors was 33% for the IP0-ID patients, a percentage significantly higher than the corresponding values for the IP-only patients (5.8%) and for the IP-only patients older than 50 years (5.7%). CONCLUSION: In patients with unsuccessful deep IP injections, superficial ID injections lead to a high percentage of false negative SLN conclusions, merely when tumours were located in the outer quadrants. Thus, it is recommended that patients with unsuccessful intra-parenchymatous and peritumoral injections of radiocolloids for tumors in outer quadrants undergo complete axillary dissection.

[Neoadjuvant radiochemotherapy and surgery of locally advanced cervical carcinoma: review of 22 patients treated at the Bordet Institute]. / Traitement par radio-chimiothérapie néoadjuvante et chirurgie du cancer du col utérin localement avancé: revue de 22 patientes à l'Institut Bordet.

OBJECTIVES: Concomitant chemoradiation is the "new gold standard" for dealing with locally advanced cervical carcinoma, but what about surgery? We don't know yet to what extent surgery is necessary and how radical it must be when it is performed. In this study, we present the analysis of the results obtained in patients treated by concomitant chemoradiation followed by radical surgery. MATERIALS AND METHODS: Twenty-two patients, median age 49 years, with I(b) - III(a) cervical tumors were enrolled to be treated by concomitant chemoradiation followed by radical surgery. The chemoradiation protocol included external radiotherapy to the pelvis: 45 Gy; Cisplatin 40 mg/m(2) in continuous intravenous infusion once a week (5 weeks) followed by brachytherapy one week later. Surgery was performed 4 to 6 weeks later and consisted in radical hysterectomy with pelvic lymphadenectomy. RESULTS: 20/22 patients underwent surgery after chemoradiation because of a diagnosis of lung metastases in one and presence of a nonresectable metastasis for the other. A complete pathological response was demonstrated in 12/20 patients (60%), a microscopic residual tumor in 7 patients (35%), and residual disease <1cm in 1 patient (5%). CONCLUSION: This study showed a particularly high rate of pathologic responses (T(0)+T(mic): 95%) and of local control. We don't know yet if surgery is a real necessity or if it could be less extended after concomitant chemoradiation.

Sentinel lymph node imaging and research after bone scintigraphy in breast cancer patients.

The aim of the study is to see if Bone Scan (BS) - when performed the day before the operation-interferes with the results of the Sentinel Lymph Node (SLN) technique using radiocolloids (their pre-operative imaging and their peroperative research). Therefore, the data of 393 patients who had one selective lymphadenectomy of the SLN(s) followed by the complete axillary node (AxN) clearance for Breast Cancer and among whom 309 patients had one BS the day before the operation (and just before the injection-s for the SLN) and 84 did not, were analysed and compared. The two series presented the same characteristics with regard to: age, clinical staging of the tumour, kind of injection-s performed (intradermic and paratumoural and/or intraparenchymal and peritumoral), pathological size of the tumour, percentage of cases with no AxN invasion, total number of AxN removed by the surgeons. The percentages of no axillary SLN visualisation, the mean numbers of axillary SLN visualised on pre-operative lymphoscintigram as well as of SLN removed by the surgeons were not statistically different in the groups of patients with (respectively, 12.11, 2.6 and 3.03) and without BS (respectively, 12.99, 2.7 and 2.96). More noteworthy, the false negative (FN) rate of the SLN technique, albeit having a higher observed value in the group with BS (9.6%, 12/125), did not differ significantly from that in the group without BS (5.6%, 2/36). The accuracies (overall correct classification rates), the sensitivities and the negative predictive values of the SLN technique also did not differ significantly between the two groups. It is concluded that the SLN technique can be accurately performed just after one BS.

How 'hot' is the pathologically positive sentinel lymph node in breast cancer patients?

When many lymph nodes are found by using lymphoscintigraphic techniques performed to detect the sentinel lymph nodes (SLNs) in breast cancer, it is usual to find that the 'hottest' SLN is not always the node that is pathologically positive (pN+). Various criteria have been proposed to define which radioactive lymph nodes should be removed. In order to determine the frequency with which the hottest SLN 'fails' to be pN+, and to determine which criteria best define the radioactive lymph node to be removed, we reviewed and analysed our cases in which more than one SLN was detected and where there was also at least one pN+ node. From a series of 181 patients, 40 were selected. In 11 of these 40 cases (27.5%), the hottest SLN was not pN+. Radioactivity levels in the pN+SLN of these 11 patients ranged from 2% to 94% of the activity of the hottest SLN. Twenty-one patients (52.5%) showed only micrometastatic (pN1a) disease in one or more SLNs. In four of these patients (19%) the pN1a SLN was not the hottest node. Two of the patients had radioactivity levels in the pN+SLN which were more than 50% of that of the hottest SLN. In another two of these patients (9.5%), radioactivity levels were lower than 50% of that of the hottest node (respectively, 38% and 2%). However, in these two last cases, the first and hottest SLN removed surgically was found, by the pathologist, to consist of six nodes. Macrometastases (dimensions greater than 2 mm) were found in 19 patients. In 12 of these patients, the hottest SLN was macrometastatic although macrometastases and/or micrometastases were found in other 'cooler' SLNs in four of them. In another seven of these patients (36.8%), macrometastases were found in SLNs with radioactive levels lower than 51% of that of the hottest node. One patient (with three SLNs) out of the 40 (2.5%) had one SLN pN+ with less than 10% of that of the hottest. In fact, it contained only one micrometastasis and its activity was equal to 2%. Upon pathological examination, however, the hottest lymph 'node' was found to consist of six nodes. It is concluded that, with four intra-mammary and peritumoural injections of 99mTc labelled nanosized colloids of Human Serum Albumin (Nanocoll R: Sorin: 74 MBq and 0.05 mg per injection) performed 18-24 h before using a gamma probe to detect the SLNs, the hottest SLN was not the pathologically positive node in 27.5% of patients in our series. By using the activity in the hottest SLN as the reference point, and 10% of this activity as the lower threshold for removing active SLNs, the sensitivity of the technique is 97.5%.

Immediate breast reconstruction with implants and adjuvant chemotherapy: a good option?

Immediate breast reconstruction using implants is a currently practiced intervention. However, it is exposed to the potential adverse effects of adjuvant therapies necessitated for cancer control. Patients with implants, receiving adjuvant chemotherapy, were compared with those not necessitating chemotherapy to evaluate the real impact of this combination of treatment modalities on the final outcome. Cosmetic results were not influenced by the adjunction of chemotherapy, but a higher rate of implant infection was observed in the chemotherapy group (10.7% versus 1.5% p = 0.0084). This observation needs to be kept in mind when selecting patients for immediate breast reconstruction with implants.

Endometrial disorders in 406 breast cancer patients on tamoxifen: the case for less intensive monitoring.

OBJECTIVES: To describe the endometrial appearance in postmenopausal breast cancer patients on tamoxifen and to assess a routine surveillance scheme for endometrial lesions. STUDY DESIGN: Three hundred and seventeen postmenopausal breast cancer women already on tamoxifen at the start of the study (group I) and 89 breast cancer women assessed before any tamoxifen intake (group II) underwent an initial and then yearly scans with transvaginal ultrasonography, followed by an hysteroscopy and biopsy for women with an endometrium thickened above 8mm. Endometrial thickness was also measured in 823 women with no breast cancer nor tamoxifen intake (group III). RESULTS: Initial mean endometrial thickness was 8.2mm in group I, 4.4mm in group II and 3.4mm in group III (P<0.001). Eighteen percent endometrial lesions were found in group I and 3.3% in group II. We observed a significant association between endometrial pathology and both cumulated dose and total duration. Polyps were the most frequent and first to appear pathology. Five cancers were detected in group I, and all of them had taken tamoxifen for more than 3 years. CONCLUSION: Our surveillance scheme could be lightened; an acceptable screening scheme might include a baseline assessment before the start of tamoxifen and, if normal, yearly screening after 3 years of tamoxifen therapy, yearly surveillance for women with an abnormal baseline assessment and immediate investigation for symptomatic women.

[Sentinel node involvement in T0-T1 breast cancers]. / Envahissement du ganglion sentinelle dans les cancers mammaires T0-T1.

STUDY AIM: Determination of axillary lymph node status is crucial in diagnosis of early breast cancer. However thanks to an early diagnosis, an increasing number of axillary lymph node dissections are free of disease. This raises questions about the need for this procedure. The study aim was to report an experience with lymphadenectomy and sentinel node mapping in patients with T0-T1 carcinoma of the breast. METHODS: Between November 1997 and December 1999, 84 consecutive women (T0-T1 N0 according to the 1987 UICC classification) with recently diagnosed breast cancer, were included in this study for identification of the sentinel lymph node (SLN). The SLN was removed and submitted for histological examination. All patients underwent axillary dissection; nodes from levels I and II (Berg's classification) were excised and submitted to histological examination. RESULTS: The average tumor diameter was 12.7 mm (range, 3 to 25 mm). The lymphatic mapping technique was obtained after injection of the isotope into the breast around the tumor in 53/84 patients: the sentinel lymph node was the only positive node in 10 patients and it was positive in 5 patients with other axillary nodes. In 15/84 patients, an intradermal injection of blue dye was used; two sentinel nodes were positive and one falsely negative. In 16/84 patients, an interdermal injection of blue dye was used to make up for. In this study, the sentinel node was positive in three patients and falsely negative in one patient. The discrepancy was due to an important involvement of an axillary area excluded from the lymphatic channels. 22/84 patients (26%) had a metastatic spread to the axillary nodes. 30/84 patients had also an isotopic captation in another lymph node group (internal mammary). CONCLUSION: This study confirms that lymphatic mapping is technically possible in the patients with T0-T1 breast cancer and that the histological characteristics of the sentinel node probably reflect the histological characteristics of the rest of the axillary lymph nodes, but do not provide any information about the other lymph node sites.

Immediate breast reconstruction with saline-filled implants: no interference with the oncologic outcome?

The possible adverse effects on cancer control due to immediate breast reconstruction have been addressed recently for both silicone-filled implants and flap reconstruction. To evaluate those possible effects after immediate breast reconstruction with saline-filled implants, 49 patients reconstructed with saline-filled breast implants at the Jules Bordet Cancer Institute were studied. Selection was only based on the possibility to find a matched patient. These patients were matched with a control group of 49 matched women with breast cancer treated in the same center by mastectomy without any type of breast reconstruction. The two groups were comparable according to age at diagnosis (within 3 years), year of diagnosis (same year), stage of the tumor, histology, and nodal status. The only difference between the two groups was that radiation therapy was applied to some of the patients who were not reconstructed (due to tumor location). The results show, in terms of local recurrences, distant metastasis, and deaths, no significant difference between the two groups, even for the irradiated patients, within a mean follow-up period of 72 months (range, 24 to 108) months.

[Breast cancer and pregnancy. Review of the literature]. / Mise au point: cancer du sein et grossesse. Revue de la littérature.

INTRODUCTION: The pregnancy-associated breast cancer seems to have become increasingly common with a high frequency of advanced breast cancer with axillary node metastases and so associated with poor prognosis. MATERIALS AND METHODS: This review examines the diagnosis, prognosis, and management of cancer during pregnancy; both in terms of the cancer's effect on the pregnancy, and the pregnancy's effect on the cancer. RESULTS: Diagnostic procedures (breast sonography) and excisional biopsies are necessary to reduce the delay of several months or more after discovery of a mass and before treatment. No histological difference, between patients with pregnancy-associated breast cancer and patients with non-pregnancy-associated breast cancer, was diagnosed. CONCLUSION: The treatment is linked to the effects of adjuvant therapy on the fetus.

Sensitivity of HER-2/neu antibodies in archival tissue samples of invasive breast carcinomas. Correlation with oncogene amplification in 160 cases.

Overexpression and amplification of the HER-2 oncogene in patients with breast cancer has correlated with early onset of metastasis, resistance to hormonal therapy and some forms of chemotherapy, and shortened survival. Therefore, evaluation of this putative prognostic or predictive factor seems critical. Because different antibodies are used for the detection of the 185-kd HER-2 oncoprotein, we studied the sensitivity of 3 frequently used antibodies. Immunohistochemistry results were correlated with gene amplification level as assessed by fluorescence in situ hybridization. Protein overexpression was found in 17.2% and 12.5% of cases using antibodies against the external (TAB250) and internal (CB11) domains of the protein, respectively, and in 38.0% of cases using a rabbit polyclonal antibody. Fluorescence in situ hybridization was successful in all 160 tumors, and amplification was found in 37 tumors (23.1%). The monoclonal antibody TAB250 had the lowest misclassification rate, 9.6% (sensitivity, 67%; specificity, 97.5%).

A multicentre study comparing cervicography and cytology in the detection of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate in a multicentre setting the performance of cervicography compared with cytology for the detection of cervical intraepithelial neoplasia. DESIGN: Prospective comparative multicentre study. SETTING: Three hospitals with outpatient gynaecology clinics and three cancer screening clinics. PARTICIPANTS AND METHODS: Cervical cytology and cervicography were performed on 5724 women. If one or both tests showed an abnormality suggestive of at least a low grade squamous intraepithelial lesion, a colposcopy with directed biopsy was carried out. Cervicograms were evaluated by four experienced 'senior' assessors and by ten new 'junior' assessors. RESULTS: Results were fully analysed for 5192 women (91%). A cervical biopsy was carried out on 228 women and this confirmed a true positive lesion in 116 cases (incidence rate: 2.2%). Of these, 72 cases (62.1%) were detected by cervicography and 64 (55.2%) by cytology. This difference was not statistically significant (McNemar: P=0.475). Only 20 cases of CIN (17%) were concordantly detected by both tests. Senior assessors performed significantly better with a detection capacity of 80.6% compared to a detection capacity of 56.6% for the junior assessors (chi2 test: P=0.034). CONCLUSIONS: Cervicography must be considered as a complementary test to cytology. Overall detection of CIN is improved, but this is mainly due to the detection of more low grade lesions. The lower sensitivity and specificity in high grade lesions compared with cervical cytology is the main limitation of cervicography in screening for CIN. An important finding was that the performance of cervicography was highly dependent on the assessors' experience.

[Breast cancer: apropos of "in situ"]. / Le cancer du sein: à propos des "In Situ".

Since the introduction of screening mammography, the proportion of ductal carcinoma in situ (DCIS) has significantly increased. Their early detection result in the majority of the cases in an exclusive radiologic expression and a histopathologic measure inferior to 20 mm. Newly formulated proposals of histologic classifications may permit in the future to identify subtypes of DCIS with a different clinical behaviour and prognosis. In analogy to the treatment's evolution for invasive mammary cancers, the concept of conservative breast surgery is evaluated in prospective randomized trials, together with the impact of adjuvant radiotherapy. Preliminary results report high survival rates, despite a considerable number of local recurrences. Radiotherapy seems not to reduce proportionally the risk for non-invasive and invasive recurrences.

Is there a role for cervicography in the detection of premalignant lesions of the cervix uteri?

The characteristics of cervicography and the Papanicolaou smear test have been compared for the detection of cervix lesions classified as CIN I or more. A total of 4,015 women were entered into the study. The sensitivity of cervicography is significantly higher (McNemar test, P < 0.0001), but its specificity remains significantly lower (McNemar test, P < 0.0001), and its higher sensitivity does not apply to lesions classified as CIN II or more (high-grade lesions). Hence, if patients with a positive screen result are to be referred for colposcopy-biopsy, cervicography is not a suitable alternative to the smear test for the screening of cervical cancer. However, cervicography can be envisaged as a complementary tool to the smear test because of (a) its higher capability to detect high-grade lesions among women less than 35 years old and (b) its potential superiority in following low-grade lesions. It may also serve as a tool for quality assurance audit of the smear test.

[Breast-preserving treatment of breast cancer and peroperative curietherapy]. / Traitement conservateur du cancer du sein et curiethérapie peropératoire.

From May 1988 to December 1990, 35 patients benefitted from a breast-conserving treatment (tumor resection with at least 1 cm of free margin, axillary dissection and peroperative brachytherapy). The iridium sources were introduced 24 h later, delivering between 15 to 17.5 Gy. Three weeks later an additional course of external radiation delivered a dose of 50 Gy in 5 weeks to the whole breast. In this series, only very early breast lesions were included and no patient received additional chemotherapy. Due to the short period of observation, we only report on the acute side effects even if until now we have not seen any case of tumor relapse. We did not observe any major complications after this combined approach: only three patients developed a local infection requiring antibiotics. Esthetic evaluation is quite encouraging with all women showing good and excellent results from the physician's and patient's points of view. This approach seems to be quite interesting cosmetically as it allows to correct the breast shape while preserving an adequate position of the implant and so preserving a good oncological approach.