C. de Bazelaire

Immunohistochemical and molecular analyses of HER2 status in breast cancers are highly concordant and complementary approaches

Background:Immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) are currently the most commonly used methods to assess HER2 status. PCR-based assays allow quantitative determination of HER2 amplification (Q-PCR) or overexpression (Q-RT–PCR), but are not routinely used. We evaluated the relevance of Q-RT–PCR for HER2 status determination.Methods:We compared IHC and Q-RT–PCR in 466 breast tumours. In discordant or equivocal cases, five additional methods (IHC with two other antibodies, FISH, silver in situ hybridisation (SISH) and Q-PCR) were combined to determine HER2 status. Two cases with HER2 intra-tumour heterogeneity were further explored by allelic profiles analysis and HUMARA clonality determination after microdissection.Results:We observed 97.3% concordance between Q-RT–PCR and non-equivocal IHC. Twelve out of 466 cases (3%) revealed discordances between the two methods. The power of Q-RT–PCR to predict HER2 status (defined by seven methods) was similar to that of IHC. Although rare, some discordances between techniques might be due to HER2 intra-tumour heterogeneity and we report two examples, one tumour containing two distinct clones, another tumour consisting of HER2 amplified and non-amplified subclones.Conclusion:Q-RT–PCR and IHC are highly concordant methods for HER2 status assessment, and Q-RT–PCR allows a highly reliable quantitative assessment and could be a useful adjunct to IHC.

CT-guided biopsies in lung infections in patients with haematological malignancies

CT-guided transparietal lung biopsy in imaging makes it possible to find the pathogenic agent in half of all fungal infections and most bacterial infections (sensitivity=55%, specificity=100%). Performance is decreased in consolidations (50% of infections) compared to masses. Complications, pneumothorax, alveolar bleeding and hemoptysis are generally benign and rarely (<5%) require specific treatment. On the other hand, the diagnostic performance increases significantly with the calibre of 18G co-axial systems compared to 20G. The risk is not related to the number of samples or platelet levels.

The Role of FDG PET for Early Prediction of Response after Two Cycles of Epirubicin + Cyclophosphamide Neoadjuvant Chemotherapy in Breast Cancer.

Background: Previous studies showed a possible role of Fluorodeoxyglucose Positron Emission Tomography (FDG PET) in monitoring response to neoadjuvant chemotherapy (NACT) in breast cancer patients. Most studies, however, mixed various chemotherapy protocols. We assessed the ability of FDG PET to predict response after two cycles of epirubicin + cyclophosphamide (EC) and compared it with histopathological response as determined by the Sataloff scale after completion of chemotherapy.Material and Methods: From 07/2007 to 05/2009, 54 patients seen at Saint Louis hospital underwent FDG PET at baseline and after the second cycle of NACT. We present data for the first 22 consecutive patients for whom pathology data are available. Standard chemotherapy treatment was four cycles of epirubicin + cyclophosphamide followed by four cycles of docetaxel. The study was performed according to the guidelines of the institutional ethical committee. The standardized uptake value (SUVmax) of FDG was measured with a PET-CT instrument at baseline and after the second cycle of chemotherapy. The change in SUV was expressed as Δ SUVmax (%) = 100 X (2 nd cycle SUVmax - baseline SUVmax)/baseline SUVmax. A Δ SUVmax cutoff value of -45% was used to differentiate metabolic responders and non-responders. Histopathological response was assessed on fresh surgical specimens (mastectomy or lumpectomy) by an experienced pathologist and graded according to the scale established by Sataloff: total or near-total therapeutic effect (grade A), more than 50% therapeutic effect but less than total or near-total effect (grade B), less than 50% therapeutic effect but visible effect (grade C), or no therapeutic effect (grade D). For the analysis, grades A and B were considered as histopathological responders and grades C and D were as non-responders.Results: Initial T-stage was T2 in 12 cases, T3 in 6 cases and T4 in 4 cases. There were 21 cases of invasive ductal carcinoma and 1 case of invasive lobular carcinoma. Mean SUVmax in initial PET was 7.22 (ranges from 2.7 to 18.5) and mean SUVmax after 2 cycles of chemotherapy was 4.77 (1.4-15.3). Breast-conserving surgery was performed in 12 patients and mastectomy in 10 patients. Nine (41%) of 22 patients were classified as histopathologic responders and 13 (59%) as non-responders. PET after two cycles of NACT revealed 9 patients (41%) as responders and 13 (59%) as non-responders. Among 9 metabolic responders, 7 were true positive, and 2 were false positive. Among 13 metabolic non-responders, 11 were true negative, and 2 were false negative. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FDG PET after two cycles of NACT were 78%, 85%, 78%, 85% and 82% respectively.Discussion: NACT has proved useful in stage II and III breast cancer, to reduce tumour volume, increasing the chance of breast-conserving surgery. In order to minimize adverse effects of NACT, non-responders must be identified as early as possible. Our preliminary results on a small series of patients show that FDG PET can differentiate responders from non-responders with good accuracy after two cycles of neoadjuvant chemotherapy with EC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5009.

Nonpalpable Breast Lesions in a Breast Care Unit: Prospective Analysis on 2708 Consecutive Cases.

Background: Breast cancer screening increases the detection of nonpalpable breast lesions, These lesions raise specific concerns, involving radiological imaging, biopsy techniques, and pathological analysis. The objective of the study is to evaluate the management of nonpalpable breast lesions in a breast disease unit.Material and Methods: From 2001 to 2007, 2708 nonpalpable breast lesions were prospectively evaluated by a multidisciplinary team. Radiologic lesions were detected by mammography alone (71,5%), ultrasonography (27,90%), MRI (0,20%). All lesions were classified according to the BI RADS classification. Three hundred and nine (309) core needle biopsies were performed, 807 vacuum assisted biopsies, and 521 open breast biopsies. The pathologic results were correlated with surgery, rebiopsy or long-term imaging follow up.Results: The pathologic results showed 33 % of malignant lesions (DCIS, invasive carcinoma), 9 % of high risk lesions (atypical ductal or lobular hyperplasia, lobular carcinoma in situ) and 58 % of benign lesions. The prevalence of cancer as a function of BI-RADS was: BI-RADS 0 : 2,6% (4/152), BI-RADS 2: 0% (0/55), BI-RADS 3: 2,3% (17/740), BI-RADS 4: 23,4% (352/1502) et BI-RADS 5 : 78,7% (185/235). Twelve of 152 (7,9 %) high risk lesions were upgraded to malignant lesions and 34/211 DCIS (16,1%) were upgraded to invasive carcinoma after surgery. Diagnostic performance rates exhibited the following results: agreement rate=96,6%, sensibility=96,2%, overall underestimation rate=12,6%, and false-negative rate=1,6%.After vacuum assisted biopsy, one-step surgery was performed in 82,9% and after core needle biopsy in 68,4%.Conclusion: This kind of quality evaluation in community practice should be encouraged. Management of those lesions continuously evolves with the widespread of RMI and new biopsy techniques. Efforts should be made in exploring imaging-pathologic discrepancies, and in identifying predictive factors of invasion on biopsies. We currently perform a focused analysis on lesions that required two surgical steps despite a prior biopsy, in order to point out new ways to improve our practices. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6020.