A radical approach to achieve complete cytoreductive surgery improve survival of patients with advanced ovarian cancer.

INTRODUCTION: Cytoreductive surgery of locally advanced ovarian cancer has evolved in the last few years from surgery to remove macroscopic residual disease (<1cm; R2b) to macroscopic complete cytoreductive surgery with no gross residual disease (R1). The aim of this study was to evaluate the impact of the adoption of a maximalist surgical approach on postoperative complications, disease recurrence and survival. MATERIALS AND METHODS: This was a retrospective study using prospectively collected data on patients who received either conservative approach (CA) or radical approach (RA) surgical treatment for primary ovarian cancer stage IIIc/IVa/IVb between June 2006 and June 2013. RESULTS: Data for 114 patients were included, 33 patients in the CA group and 68 patients in the RA group were consequently analysed. In the RA group, operative time was longer, in relation to more complex surgical procedures; with more blood losses and a higher rate of compete macroscopic resection. Totally, 77% of the patients had postoperative complications, with more grade I/II complications in the RA group but the same rates of grade III/IV complications in the both groups (P=0.14). For all patient study population, the overall and disease-free survivals were improved in case of no macroscopic residual disease. Overall survival was improved in the RA group (P=0.05), with no difference in terms of disease-free survival (P=0.29) CONCLUSION: A radical approach in advanced ovarian cancer allows a higher rate of complete cytoreductive surgery impacting overall survival. However, a non-significant trend for increased mild complications (grade I/II) rate is observed in this group.

[Not Available]. / Utilisation de la radiothérapie intra-opératoire dans le traitement conservateur d'un cas de cancer du sein invasif chez un home.

Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer cases. It is often diagnosed late, at a more advanced stage than its female counterpart. Therefore, it is more commonly treated with mastectomy. In early stages, a conservative treatment associating lumpectomy, sentinel lymph node (SLN) biopsy and whole-breast external beam radiotherapy (EBRT) is possible and has been described. Recently, intra-operative radiation therapy (IORT) has been assessed as an alternative to EBRT in selected female breast cancer cases. Its use has never been described in male patients. In this article, we present the case of a 56 years old man treated with lumpectomy with the excision of the nipple-areola complex, SLN biopsy, and IORT with electron beams (IOERT), for early breast cancer disease. This case demonstrates that the IORT technique is feasible on men with early breast cancer (pT1N0).

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.

Genome-wide gene expression profiling to predict resistance to anthracyclines in breast cancer patients.

Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-alpha (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines. Here we describe in details the contents and quality controls for the gene expression and clinical data associated with the study published by Desmedt and colleagues in the Journal of Clinical Oncology in 2011 (Desmedt et al., 2011). We also provide R code to easily access the data and perform the quality controls and basic analyses relevant to this dataset.

[Breast cancer: towards an evolution of minimalist locoregional therapy]. / Cancer du sein: vers une evolution minimaliste du traitement locorégional.

Breast cancer remains by far the most frequent cancer in women, for that matter it is the most frequent cancer in Belgium affecting both men and women. At the moment, more than 9000 cases are detected annually. The development of screening allows us, fortunately, to detect lesions and stages earlier, in that way locoregional treatmenthas considerably evolved. Since the seventies, radical mastectomy, which consists of the removal ofthe mammary gland, the axillary glands (lymph nodes) and sometimes the pectoral muscle, has been progressively replaced by conservatory treatment. This consists of a wide excision of the tumour with a safety resection margin, followed by a complete removal of the axillary glands (lymph nodes) then followed by a course of external radiotherapy testing treated six weeks daily on a five days week basis. During the nineties, in cases with certain precise indications, the complete axillary gland removal has been replaced by the removal of the first gland chain (lymph node chain) called "sentinel nodes". This technique avoids all morbidity associated to the complete lymph node removal. Finally, very recently, the classic external radiotherapy has been replaced by partial radiotherapy delivered exclusively in a few minutes during the surgical operation. Therefore, we can offer patients with early stage lesions a locoregional treatment carried out in one to two hours with an in-stay hospitalisation of two nights. This new technique manifestly offers a better locoregional control of the illness and very likely enhances (improves) their chances of recovery.

Evaluation of the histological size of the sentinel lymph node metastases using RT-PCR assay: a rapid tool to estimate the risk of non-sentinel lymph node invasion in patients with breast cancer.

A RT-PCR assay (GeneSearch™, Veridex, LLC), FDA approved and CE marked to detect metastases > 0.2 mm in sentinel lymph nodes (SLNs) is used intra-operatively for the management of patients with breast cancer. The assay provides qualitative results by applying cut-off values to cycle times (Ct) for mammaglobin (MG) and cytokeratin-19 (CK19) genes. Aims of this study were to evaluate the performance of the quantitative Ct values to estimate the size of nodal metastases and the risk of additional disease in non-SLNs. SLNs from 367 patients were clinically processed using both BLN assay and post-operative histology. Complementary axillary lymph node dissection (ALND) was performed concurrently in case of BLN assay positivity or tumour size > 2 cm. BLN positivity was reported in 19.6% of the patients for a sensitivity of 89%. BLN specificity (94.5%) and negative predictive value (97.5%) clearly demonstrated its reliability to guide ALND decision. All, except one, residual axillary metastases were found in BLN-positive patients. Considering the 78 patients with SLN positivity or discordant status according to both criteria, the metastases histological size was significantly correlated to the expression level of MG (ρ = 0.62) and CK19 (ρ = 0.64) genes (P < 10E-6). Moreover, ALND status positivity was significantly associated to Ct value of MG (z = 2.4; P = 0.018) and CK19 (z = 3.2; P = 0.001). The high intra-operative quality performance of the BLN assay minimizes the need for second surgeries for ALND. Results from this investigational study suggest that markers Ct value may provide, intra-operatively, valuable metastases size data and a risk prediction of additional disease in non-SLNs.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

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.

A significant proportion of elderly patients develop hormone-dependant "luminal-B" tumours associated with aggressive characteristics.

INTRODUCTION: To investigate the influence of ageing on the incidence of breast cancer (BC) molecular subtypes, patient age at diagnosis was correlated with bio-pathological data collected retrospectively from 2723 consecutive patients diagnosed/treated at our Institute between 2000 and 2003. METHODS: According to their bio-characteristics, 61% of the samples could be assigned to a molecular subtype: the "HER-2+", the "ER & HER2 negative" or one of the two "luminal-like" subtypes divided according to their histological grade ("A" [HER-2-/ER+/grade 1-2] and "B" [HER-2-/ER+/grade 3]). RESULTS AND CONCLUSION: Age is highly influencing the incidence of BC molecular subtypes. Patients younger than 40 develop a statistically higher rate of high grade proliferating "HER-2" (27%) and "ER & HER2 negative" (31%) BC whereas patients older than 50 develop mostly less aggressive hormone-dependant "luminal-A" BC (>67%). Nevertheless, a significant proportion of patients older than 70 develop "luminal-B" (19%) tumours associated with high proliferation, high grade, large size and nodal invasion.

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.

Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.

BACKGROUND: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. PATIENTS AND METHODS: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. RESULTS: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. CONCLUSION: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.

[Breast cancer screening]. / Le dépistage du cancer du sein.

Regarding the number of female cases (1/9) and incidence increasing, breast cancer remains the greatest public health issue. Presently, the best treatment for our patients is to screen and to treat the disease at an early stage. In our screening process " Mammotest", all women in Belgium, between 50 and 69 years, are called to a certify center every 2 years to have a mammogram. Therefore, the general practitioner has an important roll to play for a better contact in the screening process of the patients.

[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.

[Breast cancer treatment in 2004: towards a tailored approach]. / Le cancer du sein en 2004: vers une prise en charge plus personnalisée.

Breast cancer remains one of the most frequent malignancies that general practitioners are confronted with. Given their key-counselling role for the affected families, they need regular updates on the multi-disciplinary management of the disease. This has been characterized by an evolution towards less aggressive surgery, sparing many women the morbidity of a full axillary node dissection; in parallel, there is increasing hope for "individualized" adjuvant medical treatment, given the development of new technologies that provide an "identity card" of the genes expressed by each tumour. These technologies should improve our ability to identify which women truly need adjuvant chemotherapy and to select the best medical treatment on an individual basis. While providing these messages of hope, this chapter also reviews the major classes of drugs used for the treatment of advanced breast cancer.

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.