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Discrepancies have been reported between HER2 status in primary breast cancer and micrometastatic cells in bone marrow. The aim of this study was to assess HER2 gene status in micrometastatic cells in bone marrow and corresponding primary tumour. Micrometastatic cells were detected in bone marrow aspirations in a prospective series of 27 breast cancer patients by immunocytochemistry (pancytokeratin antibody). HER2 status of micrometastatic cells was assessed by fluorescence in situ hybridisation (FISH), respectively in 24 out of 27. Primary tumour HER2 status was assessed by immunohistochemistry (CB11 antibody) and by FISH in 20 out of 27 of the cases. HER2 was amplified or overexpressed in five out of 27 (18.5%) primary tumours and in four out of 27 (15%) micrometastatic cells. In two cases, HER2 was overexpressed and amplified in primary tumour, but not in micrometastatic cells, whereas, in one case, HER2 presented a low amplification rate (six copies) in micrometastatic cells not found in the primary tumour. We demonstrated that negative and positive HER2 status remained, in the majority of the cases, stable between the bone marrow micrometastasis and the primary tumour. Therefore, the efficiency of anti-HER2 adjuvant therapy could be evaluated, in a clinical trial, by sequential detection of HER2-positive micrometastatic cells within the bone marrow, before and after treatment.British Journal of Cancer (2007) 96, 654–659. doi:10.1038/sj.bjc.6603584 www.bjcancer.com Published online 30 January 2007 [ABSTRACT FROM AUTHOR]

Sastre-Garau X, Genin P, Rousseau A, Al Ghuzlan A, Nicolas A, Fréneaux P, Rosty C, Sigal-Zafrani B, Couturier J, Thiery J-P, Magdelénat H & Vincent-Salomon A (2004) Histopathology 45, 142–147 Increased cell size and Akt activation in HER-2/ neu-overexpressing invasive ductal carcinoma of the breast To determine whether cell size is related to HER-2/ neu status and/or to Akt activation in breast carcinomas. HER-2/ neu overexpression is observed in 20–30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER-2/ neu activation. Akt has been found to be involved in the HER-2/ neu signal transduction pathway and Akt activation has been associated with increased cell size in various models. A case–control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER-2/ neu overexpression and 20 HER-2/ neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin-fixed histological sections using an anti-phosphorylated-Akt (Ser473) antibody. HER-2/ neu-overexpressing carcinomas had a mean nuclear size of 75 ± 22.2 µm2 and a mean cytoplasmic size of 187 ± 52.3 µm2. Both values were higher than the nuclear and cytoplasmic size of HER-2/ neu-negative cases (nucleus = 58 ± 24.5 µm2, cytoplasm = 133 ± 56.6 µm2; P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 µm2 were HER-2/ neu-positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER-2/ neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER-2/ neu-positive and in 10% (2/19) of HER-2/ neu-negative cases ( P = 0.02). HER-2/ neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER-2/ neu-overexpressing breast carcinomas may provide useful information for optimized individual HER-2/ neu-targeted therapy. [ABSTRACT FROM AUTHOR]

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Identifies factors associated with histologically positive non-sentinel lymph nodes. Role of the sentinel node as the only involved node in the axilla for a significant proportion of women with breast cancer; Analysis of pertinent topics and relevant issues; Implications on studies of surgery.

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin…) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell–cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary. [Copyright &y& Elsevier]