Sentinel lymph node analysis in breast cancer: contribution of one-step nucleic acid amplification (OSNA).

One-step nucleic acid amplification (OSNA, Sysmex, Kobe, Japan) offers an excellent opportunity for accurate exhaustive sentinel lymph node (SLN) examination in breast cancer patients. Calibrated with conventional postoperative histology, this molecular technique yields comparable results intraoperatively, expressed as micrometastasis, macrometastasis or no metastasis depending on the CK19 mRNA copy number amplified in SLN lysates. We applied OSNA to detect metastasis in 810 SLNs from 367 patients with early stage breast cancer. We compared the rate of OSNA-positive SLNs in patients with invasive breast cancer (< 2 cm) versus the rate observed in a historical cohort using conventional histological examination of SLNs. No significant difference was observed, the OSNA assay was positive in 24.4% of patients, compared with positive histology in 24.8% in the historical cohort if including patients with isolated tumour cell (ITC) and in 23.4% excluding them. Opportunities for optimised patient management using OSNA are discussed: intraoperative detection of OSNA-positive SLNs enables axillary lymph node dissection (ALND) during the same procedure; standard OSNA techniques enable the establishment of homogeneous groups based on examination of whole SLNs for valid comparisons between different centres.

Pure flat epithelial atypia (DIN 1a) on core needle biopsy: study of 60 biopsies with follow-up surgical excision.

Flat epithelial atypia (FEA) is recognized as a precursor of breast cancer and its management (surgical excision or intensive follow-up) remains unclear after diagnosis on core needle biopsy (CNB). The aim of this study was to determine the underestimation rate of pure FEA on CNB and clinical, radiological, and pathological factors of underestimation. 4,062 CNBs from 5 breast cancer centers, performed over a 5-year period, were evaluated. A CNB diagnosis of pure FEA was made in 60 cases (1.5%) (the presence of atypical ductal hyperplasia, lobular neoplasia, radial scars, phyllodes tumor, papillary lesions, ductal carcinoma in situ or invasive carcinoma at CNB were exclusion criteria), and subsequent surgical excision was systematically performed. The histological diagnosis was retrospectively reviewed using standardized criteria and the precise terminology of the World Health Organization by two pathologist physicians. At surgical excision, 6 (10%) ductal carcinoma in situ and 2 (3%) invasive carcinoma were diagnosed. The total underestimation rate was 13%. FEA was associated with atypical ductal hyperplasia in 10 (17%) cases and with lobular neoplasia in 2 (3%) at final pathology. Residual FEA was found in 14 (23%) cases. No clinical, radiological or pathological factors were significantly associated with underestimation. Our data highlight the importance of recognizing and diagnosing FEA in core needle biopsies. Thus, the presence of FEA on CNB, even in isolation, warrants follow-up excision.

Cementoplasty for painful bone metastases: a series of 42 cases.

The aim of this study is to assess the interest of cementoplasty in the management of bone metastases, based on a retrospective study involving 42 cementoplasty procedures. The median age of the patients is 59 years, with 24 women (57%) and 18 men, all of them presenting with an advanced disease. The cementoplasty was situated in long bones (ten patients), dorsal or lumbar vertebrae (13) and flat bones (20). The principal indication was pain, sometimes with consolidation. The intensity of pain decreases between the day before and the month following the treatment (P = 0.04) among the 25 patients who had pain assessment before and after the procedure. We note 57% good results (24 patients), 9.5% failures (4 patients), and 31% with partial results (13 patients), that is, a total of 88% with "partial or full" alleviation. 16 patients out of 22 (73%) who were no longer able to walk (because of the pain or risk of fracture) were able to resume walking. We observed in this series 40.5% of complications, all of them benign. Cementoplasty improves the quality of life of patients with bone metastases, by decreasing the pain in 88% of cases and allowing the resumption of walking in almost three-quarters of the patients who had lost the ability to walk.

Atypical hyperplasia of the breast: the black hole of routine breast cancer screening.

AIM: Determination of the prevalence, of the radiological and clinical characteristics, and outcome of atypical hyperplasia (AH) of the breast within a population subjected to routine screening (double-view mammography with double reading, performed every two years between 50 and 75 years of age). PATIENTS AND METHODS: The clinical and radiological records and histological findings of percutaneous and surgical biopsy specimens of sixty-eight patients presenting with AH were reviewed together with patient follow-up data after percutaneous and surgical biopsy. RESULTS: AH incidence in the population was 0.19‰ with the following distribution of lesions: atypical epithelial hyperplasia (AEH, 53%), columnar cell metaplasia with atypia (CCMA, 32%), and lobular intraepithelial neoplasia (LIN, 8%). The mean patient age was 58 years and 24% of patients were receiving hormone replacement therapy. The main radiological finding was the presence of microcalcifications for AEH and CCMA lesions in particular, and the mammograms were valid (correlation between American College of Radiology score and risk of lesion, only 3% of lesions were recognized on the second reading). A total of 13.7% of AH cases were underestimated and a real risk of AH progression was observed, regardless of whether or not surgical biopsy had been performed. CONCLUSION: The clinical and radiological characteristics of AH observed in a population subjected to routine breast cancer screening are identical to those for patients with the same lesions referred to specialist centers. Surgical biopsy remains the recommended option due to the risk of underestimation of lesions by percutaneous biopsy and the risk of progression justifies the need for continued close monitoring.

Dosimetry based on 99mTc-macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinoma patients treated with 90Y-loaded glass microspheres: preliminary results.

UNLABELLED: Radioembolization of liver cancers using (90)Y-loaded microspheres is experiencing more widespread use. However, few data are available concerning the doses delivered to the tumors and the healthy liver. This retrospective study was conducted to calculate the tumor dosimetry (planned tumor dose [T(plan) D]) and nontumor dosimetry in patients treated by (90)Y-loaded glass microspheres and determine whether tumor dosimetry could predict response and survival. METHODS: Thirty-six patients with hepatocellular carcinoma (HCC), including 16 with portal vein thrombosis (PVT), were treated with (90)Y-loaded glass microspheres. The T(plan) D and the dose delivered to the injected healthy liver were calculated using a quantitative analysis of the (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) SPECT/CT exam. Responses were assessed after 3 mo, using the criteria of the European Association for the Study of the Liver. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier tests. RESULTS: The response rate was 69% for the overall population and 75% for the PVT patients. The dose delivered to the tumor was the only parameter associated with response with multivariate analysis (P = 0.019). A threshold T(plan) D value of 205 Gy was predictive of response, with a sensitivity of 100% and an accuracy of 91%. Quantitative (99m)Tc-MAA SPECT/CT allowed us to increase the injected activity for 4 patients with large lesions. PFS was only 5.2 mo and OS 9 mo when using a T(plan) D of less than 205 Gy versus 14 mo (P = 0.0003) and 18 mo (P = 0.0322), respectively, with a T(plan) D of 205 Gy or more. CONCLUSION: Quantitative (99m)Tc-MAA SPECT/CT is predictive of response, PFS, and OS. Dosimetry based on (99m)Tc-MAA SPECT/CT can be used for the selection of patients and for an adaptation of treatment planning, especially in selected patients (particularly in the case of large tumors). These results also confirm the efficacy and safety of (90)Y-loaded microspheres in treating HCC, even in the presence of PVT (and especially when (99m)Tc-MAA uptake is seen inside the PVT).

Intraoperative touch imprint cytology of axillary sentinel nodes for breast cancer: a series of 355 procedures.

AIMS: Our objective was to evaluate intraoperative sentinel node touch imprint cytology (IOSNTI) for breast cancer. Three hundred and fifty-five patients with invasive breast cancer (pT1N0, lobular or ductal subtype) were included in our study. IOSNTI consists of touching glass slides to the surfaces of interest after gently pressing the spatially localized specimen, taken according to predetermined conditions, in order to perform a final histological examination consisting of H&E and immunohistochemical staining. RESULTS: The total sensitivity (Se) of IOSNTI was 36% and 15% of patients with nodal metastasis went undetected during the intraoperative examination. Sensitivity was significantly lower for the oldest patients (aged over 57 years: 25%), small tumors (smaller than 12 mm: 23.3%), lobular subtypes (8.3%), in the absence of vascular emboli (33%) and for detection of micrometastases (10%). DISCUSSION: This simple, fast and relatively inexpensive method could be combined with intraoperative molecular biology methods in populations in which cytology is less efficient and produces negative results.

Differences in breast carcinoma in situ between menopausal and premenopausal women.

AIM: To seek differences between ductal carcinoma in situ (DCIS) according to the menopausal status of patients and to analyze their repercussions on patient care. PATIENTS AND METHODS: A multicenter retrospective study of 384 patients from 3 centers specialized in breast cancer surgery was carried out based on an analysis of the various characteristics (clinical, therapeutic, histologic, outcome) of DCIS between two groups of post- and pre-menopausal patients. RESULTS: At the time of diagnosis, 58.6% of the patients were menopausal. Compared to these patients, DCIS in premenopausal women was more frequently associated with initial clinical signs (p=0.006), a larger tumor size (p=0.02), involved margins after initial surgery (p=0.005), and surgical re-excision (p=0.03). The mammograms of the menopausal patients indicated a worse prognosis (using the American College of Radiology Classification) (p=0.025), and according to the histology report findings, more marked comedo necrosis (p=0.01). There was no difference in the other criteria (nuclear grade, multifocality, benign lesions associated with malignancy, relapse and its time of occurrence). The use of hormone replacement therapy had no effect on these data. CONCLUSION: The characteristics of DCIS are similar, whether occuring before or after the menopause, but the phenotypic expression is different. Menopausal status should not be a criterion for changing patient care.

Isolated skin recurrence following salvage mastectomy for intramammary recurrence (after initial breast conservation therapy): is it a fatal event?

AIMS: The authors analyzed the outcome of patients with Isolated Skin Recurrence After Salvage Mastectomy (ISRASM) performed after conservative treatment for breast carcinoma, taking into account initial tumor characteristics, intramammary recurrence (first recurrence) characteristics, local skin recurrence (second recurrence) characteristics, and the type of treatment at each stage of the breast cancer continuum. METHODS: Forty-two patients who had ISRASM between 1976 and 2007 were included in this retrospective study. Twenty-six factors were studied in univariate and multivariate analyses. RESULTS: Mean Overall Survival (OS) was 70.3 (±4.1) months. The 5-year OS rate was 66.6%. 31% of patients did not present any recurrence, 52% had locoregional recurrence and 14% metastatic recurrence following ISRASM. Univariate analysis showed that 4 prognostic factors were significantly related to OS and/or Disease-Free Survival (DFS): (1) initial chemotherapy after primary breast cancer (P = 0.09 and 0.01 respectively), (2) presence of emboli at the site of intramammary recurrence (first recurrence) (P = 0.02 and 0.03), (3) interval between first and second surgery of less than 3 years (P = 0.09 and 0.0003), and (4) inflammatory skin involvement at ISRASM (P = 0.005 and 0.17). Multivariate analysis showed that presence of emboli at the site of intramammary recurrence was significantly related to OS and that an interval between first and second recurrence of less than 3 years was significantly related to DFS. CONCLUSION: Our results show that ISRASM affects a group of breast cancer patients with predominantly local rather than metastatic disease. Prognostic factors depend on characteristics at initial breast cancer, first recurrence and second recurrence. Evidence-based guidelines are still required for ISRASM management.

Utility of Quantitative Tc-MAA SPECT/CT for yttrium-Labelled Microsphere Treatment Planning: Calculating Vascularized Hepatic Volume and Dosimetric Approach.

Objectives. The aim of this study was to assess the effectiveness of SPECT/CT for volume measurements and to report a case illustrating the major impact of SPECT/CT in calculating the vascularized liver volume and dosimetry prior to injecting radiolabelled yttrium-90 microspheres (Therasphere). Materials and Methods. This was a phantom study, involving volume measurements carried out by two operators using SPECT and SPECT/CT images. The percentage of error for each method was calculated, and interobserver reproducibility was evaluated. A treatment using Therasphere was planned in a patient with three hepatic arteries, and the quantitative analysis of SPECT/CT for this patient is provided. Results. SPECT/CT volume measurements proved to be accurate (mean error <6% for volumes ≥16 cm(3)) and reproductive (interobserver agreement = 0.9). In the case report, (99m)Tc-MAA SPECT/CT identified a large liver volume, not previously identified with angiography, which was shown to be vascularized after selective MAA injection into an arterial branch, resulting in a large modification in the activity of Therasphere used. Conclusions. MAA SPECT/CT is accurate for vascularized liver volume measurements, providing a valuable contribution to the therapeutic planning of patients with complex hepatic vascularization.

Effectiveness of quantitative MAA SPECT/CT for the definition of vascularized hepatic volume and dosimetric approach: phantom validation and clinical preliminary results in patients with complex hepatic vascularization treated with yttrium-90-labeled microspheres.

The goal of this study was to assess the use of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) analysis for vascularized volume measurements in the use of the yttrium-90-radiolabeled microspheres (TheraSphere). A phantom study was conducted for the validation of SPECT/CT volume measurement. SPECT/CT quantitative analysis was used for the measurement of the volume of distribution of the albumin macroaggregates (MAA; i.e., the vascularized volume) in the liver and the tumor, and the total activity contained in the liver and the tumor in four consecutive patients presenting with a complex liver vascularization referred for a treatment with TheraSphere. SPECT/CT volume measurement proved to be accurate (mean error <7%) and reproducible (interobserver concordance 0.99). For eight treatments, in cases of complex hepatic vascularization, the hepatic volumes based on angiography and CT led to a relative overestimation or underestimation of the vascularized hepatic volume by 43.2 ± 32.7% (5-87%) compared with SPECT/CT analyses. The vascularized liver volume taken into account calculated from SPECT/CT data, instead of angiography and CT data, results in modifying the activity injected for three treatments of eight. Moreover, quantitative analysis of SPECT/CT allows us to calculate the absorbed dose in the tumor and in the healthy liver, leading to doubling of the injected activity for one treatment of eight. MAA SPECT/CT is accurate for volume measurements. It provides a valuable contribution to the therapeutic planning of patients presenting with complex hepatic vascularization, in particular for calculating the vascularized liver volume, the activity to be injected and the absorbed doses. Studies should be conducted to assess the role of quantitative MAA/SPECT CT in therapeutic planning.

Patient age and positive margins are predictive factors of residual tumor on mastectomy specimen after conservative treatment for breast cancer.

AIMS: To determine factors predictive of the presence of residual tumor on the specimen from mastectomy performed after conservative treatment for breast cancer in order to limit potentially unnecessary mastectomies (free of residual lesions). MATERIALS AND METHODS: 294 patients treated in 2 expert centers for breast cancer with breast-conserving therapy (BCT) followed by mastectomy, according to French recommendations, were investigated between January 1, 1998 and January 1, 2005. Patients with residual tumor on the mastectomy specimen were compared with patients whose mastectomy specimens did not reveal any residual tumor. All the clinical risk factors (age, previous history of breast cancer, tumor focality) and histological risk factors (tumor size, histological type, positive margins, estrogen and progesterone receptor expression, histological grade) for residual tumor after BCT were compared between the 2 patient groups. RESULTS: Of the 294 patients studied, 202 (68.71%) mastectomies had residual tumor and 92 (31.29%) were tumor-free. Four predictive factors for residual tumor were found in the univariate analysis: age under 45 years (p=0.01), absence of estrogen receptor expression (p=0.05), positive margins (p=0.01), and presence of lymph node metastases (p=0.05). The multivariate analysis revealed only 2 independent risk factors that were significantly associated with increased risk of residual tumor on the mastectomy specimen: age under 45 years (p=0.05) and presence of positive margins on the lumpectomy specimen (p=0.05). CONCLUSION: Young age of patients (under 45-years-old) and presence of positive margins on the operative specimen are independent risk factors of residual tumor after conservative treatment of breast cancer.