Breast 2006 May 19; (Read article online)

Crowe JP, Patrick RJ, Rybicki LA, Escobar PF, Weng D, Thomas Budd G, Tubbs RR, Procop GW, Hicks DG

Recently published clinical trial data have produced compelling evidence for increased survival when Herceptin is administered to patients whose tumors are HER2 amplified. Therefore, the accuracy of HER2 status is essential to determine which patients should or should not receive Herceptin. Although HER2 results obtained by FISH and IHC are often in agreement, there is a persistent group of cases in which results are discordant, particularly among tumors with intermediate results. A multivariable analysis was undertaken to determine relative significance of various clinical and pathologic findings for patients diagnosed with infiltrating ductal carcinoma, and a data model was produced that predicts which patients are most likely to have HER2 amplified tumors. Correlates of HER2 amplification were higher Scarff-Bloom-Richardson grade, younger age at diagnosis, and a comedo ductal carcinoma in situ component.

J Plast Reconstr Aesthet Surg 2006; 59(6): 614-21 (Read article online)

Granzow JW, Levine JL, Chiu ES, Allen RJ

BACKGROUND: Several alternatives exist for breast cancer reconstruction with perforator flaps. For those patients in whom the buttock is the best choice as a source for autologous tissue, the IGAP and SGAP flaps are an excellent option. These flaps allow the reliable transfer of skin and soft tissue from the buttock without the associated donor site morbidity of a muscle flap. INDICATIONS: Most women requiring tissue transfer to the chest from the buttock for breast reconstruction or other reasons are candidates for IGAP or SGAP flaps. Do to an improved donor site contour and scar, we now prefer to use the IGAP to the SGAP flap. Absolute contraindications specific to perforator flap breast reconstruction in our practice include history of previous liposuction of the donor site or active smoking (within 1 month prior to surgery). ANATOMY AND TECHNIQUE: IGAP and SGAP flaps are based on perforators from either the superior or inferior gluteal artery. These perforators are carefully dissected free from the surrounding gluteus maximus muscle, which is spread in the direction of the muscle fibres and safely preserved. The vascular pedicle is anastomosed to recipient vessels in the chest and the donor site closed primarily. CONCLUSIONS: IGAP and SGAP flaps allow the safe and reliable transfer of tissue from the buttock for breast reconstruction as an alternative to soft tissue transfer from an abdominal donor site or even as a first choice in selected patients.

Radiat Med 2006 Feb; 24(2): 108-14 (Read article online)

Sundararajan S, Tohno E, Kamma H, Ueno E, Minami M

PURPOSE: The purpose of this study was preoperatively to diagnose the intraductal component, which is indispensable in planning for breast conservation therapy, and also to minimize local recurrence. This study investigated the efficacy of ultrasound (US) in the detection of intraductal component in comparison with magnetic resonance imaging (MRI) and histopathological findings. PATIENTS AND METHODS: In 47 patients with invasive breast cancer, US features of the intraductal component were classified as (a) solid ductal dilatation radiating from the tumor, (b) presence of satellite lesion in the same segment without ductal dilatation, and (c) ductal dilatation between the main tumor and satellite lesion. MRI depicted intraductal extension as the most enhanced area during the first or second phase of the dynamic study. Other criteria for the detection of the intraductal component by MRI were as follows: (a) a satellite lesion around the main tumor, (b) bridging enhancement between the main tumor and satellite lesions. The extent of the intraductal component was measured and classified as mimimal (0-5 mm), moderate (6-15 mm) or wide (>15 mm). RESULTS: In 28 of 47 (60.0%) patients, a wide intraductal component of more than 15 mm was proved histopathologically. Of 28 patients, US and MRI could accurately detect wide intraductal components in 16 patients and 14 patients, respectively. Sensitivity, specificity, and accuracy were 57.1%, 84.2%, and 68.1% respectively for US and 50.0%, 89.5% and 65.9% for MRI, respectively. When both US and MRI results were combined, sensitivity, specificity, and accuracy were 75.0%, 84.2%, and 78.7%. CONCLUSION: Current US examination depicted the intraductal component of breast cancer more accurately than MRI. Further, our study suggests that the use of both US and MRI together is complementary and offers more advantage than US alone.

Radiat Med 2006 Jan; 24(1): 35-40 (Read article online)

Yamamoto A, Fukushima H, Okamura R, Nakamura Y, Morimoto T, Urata Y, Mukaihara S, Hayakawa K

PURPOSE: The purpose of this study was to determine whether dynamic helical computed tomography (CT)-mammography could assist in selecting the most appropriate surgical method in women with breast cancer. MATERIALS AND METHODS: Preoperative contrast-enhanced helical CT scanning of the breast was performed on 133 female patients with suspicion of breast cancer at the same time as clinical, mammographic, and/or ultrasonographic examinations. The patients were scanned in the prone position with a specially designed CT-compatible device. A helical scan was made with rapid intravenous bolus injection (3 ml/s) of 100 ml of iodine contrast material. Three-dimensional maximum intensity projection (MIP) images were reconstructed, and CT findings were correlated with surgical and histopathological findings. RESULTS: Histopathological analysis revealed 84 malignant lesions and seven benign lesions. The sensitivity, specificity, and accuracy levels of the CT scanning were 94.6%, 58.6%, and 78.9%. Helical scanning alone revealed additional contralateral carcinomas in three of four patients and additional ipsilateral carcinomas in three of five patients. However, the technique gave false-positive readings in 24 patients. The preoperative CT-mammogram altered the surgical method in six patients. CONCLUSION: Dynamic helical CT-mammography in the prone position may be one of the choices of adjunct imaging in patients with suspected breast cancer scheduled for surgery.

Radiat Med 2006 Jan; 24(1): 77-9 (Read article online)

Murata Y, Ogawa Y, Yamawaki Y, Kohsaki S, Kubota K, Nishioka A, Yoshida S, Tochika N

We describe a 53-year-old woman with tumor marker abnormality caused by an umbilical metastasis from breast cancer. She had undergone breast conservation therapy (BCT) for breast cancer (T2N1M0) 9 years previously. Umbilical metastasis was detected 9 months after tumor marker elevation was first noted. After resection of the umbilical metastasis, tumor marker level decreased immediately and normalized. The patient is alive without other metastasis.

J Clin Oncol 2006 May 22; (Read article online)

Cachin F, Prince HM, Hogg A, Ware RE, Hicks RJ

PURPOSE: This study examines the use of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of the therapeutic response for patients treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation for metastatic breast cancer (MBC) focusing on prognostic stratification. PATIENTS AND METHODS: Forty-seven patients with MBC were treated with a maximum of three cycles of HDC. Therapeutic response was assessed with conventional imaging (CImg; including a computed tomography in all cases and ultrasound, mammography, and bone scanning as clinically indicated) and by FDG-PET study performed after the last cycle of HDC. Parameters analyzed for predicting survival were FDG-PET and CImg results, pattern of disease, prior treatment, and HDC regimen. RESULTS: Complete responses were observed in 16 patients (37%) with CImg and 34 patients (72%) with FDG-PET. The FDG-PET result was the most powerful and independent predictor of survival; patients with a negative post-treatment FDG-PET had a longer median survival than patients with a positive FDG-PET (24 months v 10 months; P < .001). By multivariate analysis the relative risk (RR) of death was higher in patients with FDG-PET-positive disease (RR, 5.3), prior anthracycline treatment (RR, 3.3), or with visceral metastasis (RR, 2.4). CONCLUSION: A single FDG-PET study performed after completion of HDC for MBC can powerfully stratify for survival. This may have implications for how we should assess outcome after conventional-dose therapy for MBC and warrants additional study.

Toxicol Appl Pharmacol 2006 May 20; (Read article online)

Silva E, Lopez-Espinosa MJ, Molina-Molina JM, Fernández M, Olea N, Kortenkamp A

Prompted by reports about strong estrogenic effects of cadmium, attempts were made to reproduce these observations using the yeast estrogen screen (YES) and the E-Screen assays. For the first time, possible activation of the Src/MAPK pathway was also investigated. In the YES, only a slight activation (10% of a maximal effect) of the estrogen receptor alpha (ERalpha) was observed at cadmium concentrations between 5 x 10(-7) M and 5 x 10(-6) M. In the E-Screen assay, carried out by two laboratories, the heavy metal was without observable cell proliferative effects when tested in the range between 6 x 10(-11) M and 1 x 10(-5) M. However, in both assays, cadmium led to a reduction of the effects of 17beta-estradiol (E2). Treatment of MCF-7 human breast cancer cells with 1 x 10(-7) M cadmium failed to induce phosphorylation of Src and the MAP kinases Erk1 and Erk2-effects shown to occur with E2 and epidermal growth factor (EGF). In summary, we were unable to confirm the strong estrogenicity of cadmium reported recently by a number of laboratories. This apparent absence of effects in our hands is not due to a lack of uptake of the metal or to effective protection against cadmium by high levels of glutathione or metallothionein, since toxicity and an antagonism of E2 responses were observed both in the YES and the E-Screen.

J Plast Reconstr Aesthet Surg 2006; 59(6): 585-93 (Read article online)

Alonso-Burgos A, García-Tutor E, Bastarrika G, Cano D, Martínez-Cuesta A, Pina LJ

BACKGROUND: Autologous breast reconstruction with abdominal tissue is one of the best options after mastectomy. Reconstruction with deep inferior epigastric perforator (DIEAP) flaps requires a precise location and preoperative evaluation of perforating vessels. The objective of this report is to demonstrate the usefulness of multislice-CT (MSCT) angiography for preoperative planning in patients undergoing DIEAP flap reconstruction. METHODS: Six consecutive women were considered for breast reconstruction with DIEAP flaps after previous mastectomy for breast cancer. Preoperative MSCT angiography was performed to localise the arterial perforators. Axial images, multiplanar reconstructions (MPR) and 3D volume-rendered images were analysed. Findings were correlated with surgery. Initial experience and imaging findings will be described. RESULTS: Accurate identification of the main perforators was achieved in all six patients with a very satisfactory concordance between MSCT angiography and surgical findings. No unreported vessels were found. Location, course, anatomical variations and relations of the superficial inferior epigastric artery were reported. The very small perforators, were equally evaluated and described. CONCLUSIONS: Preoperative evaluation of perforator arteries with MSCT angiography is feasible in patients undergoing breast reconstruction. This technique provides a noninvasive global approach of the vascular anatomy and the entire anterior abdominal wall. However, more patients need to be evaluated in order to clarify the potential aspects pointed in this report.

Rheum Dis Clin North Am 2006 May; 32(2): 383-400 (Read article online)

Molloy ES, McCarthy GM

Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate crystals are the most common types of pathologic calcium-containing crystals. Although these crystals long have been associated with a variety of rheumatic syndromes, recent evidence implicates BCP crystals in the pathogenesis of breast cancer and atherosclerosis. Although understanding of molecular mechanisms involved in generating these pathologic effects has been advanced significantly in recent years, they still are understood incompletely. Such advances are essential to the ongoing search for effective therapies for crystal-associated diseases.

Rapid Commun Mass Spectrom 2006 May 19; 20(12): 1954-1962 (Read article online)

Mareck U, Geyer H, Guddat S, Haenelt N, Koch A, Kohler M, Opfermann G, Thevis M, Schänzer W

Anastrozole (2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1.3-phenylene]bis(2-methylpropionitrile)) and exemestane (6-methylenandrostan-1,4-diene-3,17-dione) are therapeutically used to treat hormone-sensitive breast cancer in postmenopausal women. For doping purposes they may be used to counteract adverse effects of an extensive abuse of anabolic androgenic steroids (gynaecomastia) and to increase plasma testosterone concentrations. Excretion study urine samples and spot urine samples from women suffering from metastatic breast cancer, being treated with anastrozole or exemestane, were collected and analyzed to develop/optimize a detection system for anastrozole and exemestane to allow the identification of athletes who do not comply with the internationally prohibited use of these cancer drugs. The assay was based on liquid-liquid extraction after enzymatic hydrolysis following liquid chromatography/tandem mass spectrometry (LC/MS/MS). Anastrozole, exemestane and its main metabolite (17-dihydroexemestane) were identified in urine by comparison of mass spectra and retention times with respective reference substances. An assay validation for the analysis of anastrozole and exemestane was performed regarding lower limits of detection (anastrozole: 0.02 ng/mL; exemestane: 3.1 ng/mL; dihydroexemestane: 0.5 ng/mL), interday precisions (6.6-11.1%, 4.9-9.1% and 5.6-8.3% for low [10 ng/mL], medium [50 ng/mL] and high [100 ng/mL] concentration) and recoveries (ranged from 85-97%). Copyright (c) 2006 John Wiley & Sons, Ltd.

Cancer Chemother Pharmacol 2006 May 23; (Read article online)

Ardavanis A, Mavroudis D, Kalbakis K, Malamos N, Syrigos K, Vamvakas L, Kotsakis A, Kentepozidis N, Kouroussis C, Agelaki S, Georgoulias V,

Purpose: To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. Patients and treatment: Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performance status of 0-1, 30 (83%) had visceral disease and 83% had received prior taxanes while 50% anthracyclines. Treatment consisted of pegylated liposomal doxorubicin (40 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 15) every 4 weeks. Results: In an intention-to-treat analysis 2 (6%) complete and 12 (33%) partial responses were observed (overall response rate 39%; 95% CI: 23-54.8%); 8 (22%) and 14 (39%) patients experienced stable and progressive disease, respectively. The median TTP was 6.5 months and the median survival time 14.2 months. The 1-year survival rate was 54.1%. Grade 3 and 4 neutropenia occurred in 21 (58%) patients, grade 3-4 anemia in four (11%) and grade 4 thrombocytopenia in one (3%). Two (6%) patients developed febrile neutropenia. Non-hematologic toxicity was mild and easily manageable. There was no clinically important cardiac toxicity or treatment-related deaths. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated salvage regimen in patients with metastatic breast cancer which merits further evaluation.

Mol Cell Biochem 2006 May 23; (Read article online)

Dinesh KP, Devaraj H, Murugan V, Rajaraman R, Niranjali S

BRCA1 is a tumour suppressor gene (TSG), which predisposes cancer to both breast and ovary. The primary objective of the present study is to ascertain the involvement of BRCA1 gene in the pathogenesis of sporadic breast cancer women in Chennai (South India) by analysing its protein expression by immunohistochemistry (IHC) and loss of heterozygosity (LOH) for confirmation of the involvement of TSG in the study population. We found down regulation of BRCA1 protein (54%) in IHC and it was correlated with the clinicopathological parameters of the patients. We found near significant correlation (P < 0.063) between BRCA1 protein expression and clinicopathological parameters. We found 30% LOH in our study and it was also correlated with the clinicopathological parameters. No correlation was found between LOH and clinicopathological parameters. Though we found no correlation, the results revealed in this study support the involvement of BRCA1 TSG in the pathogenesis of sporadic breast cancer women in Chennai (South India).

J Plast Reconstr Aesthet Surg 2006; 59(6): 644-52 (Read article online)

Hamdi M, Van Landuyt K, de Frene B, Roche N, Blondeel P, Monstrey S

INTRODUCTION: Anatomy and classification of intercostal perforator flaps in addition to our experience with will be demonstrated for different indications. MATERIAL AND METHODS: The intercostal vessels form an arcade between the aorta and the internal mammary vessels. Different pedicled perforator flaps can be raised on this neurovascular bundle to cover defects on the trunk. They are classified as following: dorsal intercostal artery perforator flap (DICAP); lateral intercostal artery perforator (LICAP); and anterior intercostal artery perforator (AICAP) flap. RESULTS: Between 2001 and 2004, 20 pedicled (ICAP) flaps were harvested in 16 patients. The indications were: immediate partial breast reconstruction in eight patients who had a quadrantectomy for breast cancer; midline back and sternal defects in three patients who had radical excisions for a dermatofibrosarcoma or malignant melanoma; and autologous breast augmentation (four bilateral and one unilateral flap) in five post-bariatric-surgery patients. The average flap dimension was 18x8cm(2) (range 8x5-24x12cm(2)). There were two DICAP flaps, two (AICAP) flaps and 16 (LICAP) flaps. All but two flaps were based on one perforator. Mean harvesting time was 45min for a single flap. Bilateral breast augmentation with LICAP flap necessitated longer operative time (range 2-3h) depending whether it was combined or not with mastopoexy. Complete flaps survival was obtained. All donor sites were closed primarily. CONCLUSION: The (ICAP) flaps provide valuable options in breast surgery; and for challenging defects on the trunk without sacrifice of the underlying muscle.

World J Surg 2006 May 19; (Read article online)

Wolfort RM, Li BD, Johnson LW, Turnage RH, Lilien D, Ampil F, Burton G, Chu QD

BACKGROUND: The role of whole-body fluorine-18-FDG positron emission tomography (FDG-PET) as an adjunct localize recurrence in stages II and III breast cancer patients who present with clinical suspicion for recurrence is not well established. We report our experience in such a patient population. METHODS: A retrospective review of all patients with stages II and III breast cancer who had a whole-body FDG-PET scan was performed. RESULTS: Of the 23 patients who fit the criteria, 9 had stage II and 14 had stage III breast cancer. Overall sensitivity, specificity, and accuracy were 81%, 100%, and 87%, respectively. Positive and negative predictive values for stages II and III were 100% and 83%, respectively, and 100% and 50%, respectively. FDG-PET detected two recurrences that were missed by conventional imagings, but such recurrences were local and amenable for biopsy. CONCLUSIONS: In patients with stages II and III breast cancer who present with a suspicion for recurrent disease, a whole-body FDG-PET scan may be a useful adjunct in the evaluation of recurrence. However, its added benefit over conventional imaging should be questioned.

Eur J Nucl Med Mol Imaging 2006 May 23; (Read article online)

Carlsson J, Eriksson V, Stenerlöw B, Lundqvist H

PURPOSE: The purpose of this study was to identify combinations of dose rate and exposure time that have the potential to provide curative treatment with targeted radionuclide therapy applying low dose rate beta irradiation. METHODS: Five tumour cell lines, U-373MG and U-118MG gliomas, HT-29 colon carcinoma, A-431 cervical squamous carcinoma and SKBR-3 breast cancer, were used. An experimental model with 10(5) tumour cells in each sample was irradiated with low dose rate beta particles. The criterion for successful treatment was absence of recovery of cells during a follow-up period of 3 months. The initial dose rates were in the range 0.1-0.8 Gy/h, and the cells were continuously exposed for 1, 3 or 7 days. These combinations covered dose rates and doses achievable in targeted radionuclide therapy. RESULTS: Continuous irradiation with dose rates of 0.2-0.3 and 0.4-0.6 Gy/h for 7 and 3 days, respectively, could kill all cells in each tumour cell sample. These treatments gave total radiation doses of 30-40 Gy. However, when exposed for just 24 h with about 0.8 Gy/h, only the SKBR-3 cells were successfully treated; all the other cell types recovered. There were large cell type-dependent variations in the growth delay patterns for the cultures that recovered. The U-118MG cells were most resistant and the U-373MG and SKBR-3 cells most sensitive to the treatments. The HT-29 and A-431 cells were intermediate. CONCLUSION: The results serve as a guideline for the combinations of dose rate and exposure time necessary to kill tumour cells when applying low dose rate beta irradiation. The shift from recovery to "cure" fell within a narrow range of dose rate and exposure time combinations.

Cancer 2006 May 22; (Read article online)

Feigelson HS, Patel AV, Teras LR, Gansler T, Thun MJ, Calle EE

BACKGROUND: Although the link between postmenopausal breast cancer and adiposity is well established, the association between weight gain and specific histopathologic characteristics of breast carcinoma has not been studied carefully. METHODS: Using 1200 incident invasive breast cancers among 44,161 postmenopausal women who were not taking hormone therapy in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort, the authors computed age-adjusted rates and rate ratios (RR) for breast cancer by histology, stage, grade, and estrogen receptor (ER) and progesterone receptor (PR) status by categories of adult weight gain. RESULTS: Age-adjusted rates of breast cancer were highest for women who reported the most weight gain, regardless of histologic type. For weight gain >60 pounds, compared with weight gain

Cancer 2006 May 17; (Read article online)

Tward JD, Wendland MM, Shrieve DC, Szabo A, Gaffney DK

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) are at increased risk for developing secondary malignancies. For the current study, the authors quantitated this risk in a group of NHL survivors over 30 years of follow-up. METHODS: Standardized incidence ratios (observed-to-expected [O/E] ratio) and absolute excess risk of secondary malignancies were assessed in 77,876 patients who were diagnosed with NHL between 1973 and 2001 from centers that participated in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: There were 5638 patients who developed secondary malignancies, significantly more than the endemic rate (O/E, 1.14; P<.001). Overall, irradiated patients had a similar risk of secondary malignancies compared with unirradiated patients (relative risk, 1.04; 95% confidence interval, 0.98-1.10; P = .21). Irradiated patients had excess risk for sarcomas, breast cancers, and mesothelioma compared with unirradiated survivors (P<.05). Patients age <25 years at the time of their NHL diagnosis had the highest relative increased risk (no radiation: O/E, 2.1; P<.05; radiation: O/E, 4.51; P<.05). Overall, no statistical difference was observed for secondary cancer incidence between females and males (O/E, 1.12 vs. 1.15, respectively). Female survivors of NHL were less likely to develop breast cancer than the general population (O/E, 0.85; P<.05), but women age <25 years at the time of their NHL diagnosis were more likely to develop breast cancer (no radiation: O/E, 2.1; P<.05; radiation: O/E, 4.51; P<.05). CONCLUSIONS: The overall risk of secondary malignancies was increased for NHL survivors and varied according to age at NHL diagnosis, gender, and treatment. Cancer 2006. (c) 2006 American Cancer Society.

Neurosurg Focus 2006; 20(4): e27 (Read article online)

Tunici P, Irvin D, Liu G, Yuan X, Zhaohui Z, Ng H, Yu JS

The observation of similarities between the self-renewal mechanisms of stem cells and cancer cells has led to the new concept of the cancer stem cell. In cases of leukemia, multiple myeloma, and breast cancer, cells with a high selfrenewal potential have been identified. Furthermore, investigators have shown these cells' ability to drive the formation and growth of the tumor. Brain tumors have also been reported to possess a subpopulation of cancer stemlike cells that have the ability to proliferate, self-renew, and be multipotent. When grafted into mice, these cells are also able to generate a tumor that recapitulates that of the patient from whom the cells were derived. The identification and characterization of this new category of cells call for new therapies capable of selectively targeting and killing these multifaceted cells.

J Clin Oncol 2006 May 20; 24(15): 2276-2282 (Read article online)

Perik PJ, Lub-De Hooge MN, Gietema JA, van der Graaf WT, de Korte MA, Jonkman S, Kosterink JG, van Veldhuisen DJ, Sleijfer DT, Jager PL, de Vries EG

PURPOSE The cardiac and antineoplastic effects of trastuzumab may be related to specific uptake of trastuzumab in myocardium and tumor tissue, respectively. We evaluated whether indium-111 ((111)In) -labeled trastuzumab scintigraphy can predict cardiotoxicity and identify tumor lesions. In addition, we evaluated whether plasma markers for cardiac dysfunction can be used to predict cardiotoxicity. PATIENTS AND METHODS Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer underwent gamma camera imaging from 15 minutes to 7 days after injection of 150 MBq (111)In-diethylenetriamine penta-acetic acid anhydride (DTPA) -trastuzumab, after loading-dose trastuzumab, and after once-a-week trastuzumab doses for 11 weeks, and concomitant paclitaxel once every 3 weeks. Cardiac assessments were performed before treatment, and after four and six cycles. Plasma N-terminal probrain natriuretic peptide (NT-proBNP) and serum troponin I were measured with immunoassay. Results Fifteen of the 17 patients were available for cardiac and tumor uptake analysis. On the first scan, myocardial (111)In-DTPA-trastuzumab uptake was observed in one patient with pre-existing cardiac arrhythmias, who did not develop heart failure during treatment. Severe cardiotoxicity occurred in three patients, without initial myocardial uptake, whereas one showed weak myocardial uptake after four cycles. The detection rate of single tumor lesions was 45%. New tumor lesions were discovered in 13 of 15 patients. Pretreatment plasma NT-proBNP levels were higher in patients with than without heart failure (mean, 534 [standard deviation, 236] v 105 [standard deviation, 79] ng/L; P = .009). CONCLUSION Radiolabeled trastuzumab scintigraphy was not valuable in predicting trastuzumab-related cardiotoxicity in metastatic breast cancer patients, but can identify HER2-positive tumors. Measurement of plasma NT-proBNP is promising regarding prediction of trastuzumab-related cardiotoxicity.

J Pathol 2006 May 18; (Read article online)

Hennard C, Pfuhl T, Buettner M, Becker KF, Knöfel T, Middeldorp J, Kremmer E, Niedobitek G, Grässer F

We have previously developed two monoclonal antibodies against the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1), designated 1H4 and 2B4. Both detect EBNA1 by in situ staining in established EBV-positive tumours, e.g. Hodgkin's lymphoma and nasopharyngeal carcinoma. An association of EBV with other tumours, notably breast carcinomas, has been reported but remains controversial. Using the antibody 2B4, a nuclear protein has been detected in breast carcinomas that were EBV-negative by other methods, suggesting cross-reactivity with a cellular protein. Furthermore, an association of EBV with various other carcinomas has been reported on the basis of 2B4 immunohistochemistry. Here we show that 2B4 also binds to MAGE-4, a cancer testis antigen expressed in a variety of tumour cells, including breast carcinoma, seminoma and EBV-negative cases of Hodgkin's lymphoma. We conclude that the 2B4 antibody is not suitable for the detection of EBV infection but that additional techniques, particularly in situ hybridization for the detection of the EBV-encoded RNAs (EBERs), should be employed to confirm the presence of EBV. Our results add to the evidence indicating that breast cancer is not an EBV-associated disease. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.