Elsevier

European Journal of Cancer

Volume 40, Issue 3, February 2004, Pages 336-341
European Journal of Cancer

Wide metastatic spreading in infiltrating lobular carcinoma of the breast

https://doi.org/10.1016/j.ejca.2003.08.007Get rights and content

Abstract

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.

Introduction

Metastatic spread represents a severe complication of breast cancer, but the biological factors related to epithelial cells ability to migrate and develop in distant organs remains unidentified. Our aim was to determine whether phenotypic traits could characterise the metastatic potential of breast cancers. Invasive ductal (IDC) and lobular (ILC) carcinomas represent 80 and 10% of breast carcinomas, respectively. IDC are composed of cells arranged in more or less well formed glandular structures 1, 2, whereas ILC correspond to a proliferation of non-cohesive small cells irregularly dispersed in a fibrous stroma 3, 4, 5, 6, 7, 8, 9. ILC are also defined by clinical 8, 10 and radiological [11] characteristics, and by clinico-biological features such as a high rate of hormonal receptor expression 8, 12, a low cell-proliferation rate 9, 13 and a low frequency of ERBB2 overexpression 14, 15.

Clinico-pathological analyses have shown that the overall outcome of ILC did not significantly differ from that of the common IDC type 16, 17 and that these tumours could be treated similarly 8, 18. However, several studies have emphasised that ILC was characterised by a peculiar pattern of metastatic dissemination. Compared with IDC, a lower incidence of spreading to the lung and a higher incidence to the bone and to gastrointestinal tract were observed in ILC 8, 19, 20, 21. The molecular mechanisms underlying these differences have not been elucidated. Nonetheless, it has been suggested that the loss of the E-cadherin function, a cell–cell adhesion molecule frequently altered in ILC [22], could account for the state of non-cohesive epithelial tumour cells 23, 24, 25, 26 and that this may play a part in local and metastatic tumour progression 27, 28. Successive histological studies have also documented the morphological heterogeneity of ILC. Besides the classical histological form corresponding to early descriptions, variants have been defined, recognised either by their characteristic architectural pattern, namely alveolar 5, 29, 30, solid 31, 32 or tubulo-lobular [33], or by cytopathological features, signet ring cells [34] and pleomorphic 35, 36, 37, 38. Few data are available on the respective metastatic potential of these histological entities.

Our aim was to determine whether the metastatic potential of breast carcinomas could be related to the phenotypic characteristics of the tumour. We therefore compared the metastatic patterns of ILC and IDC and then we analysed this pattern in the group of ILC according to the histological characteristics of the primary.

Section snippets

Patients and methods

The cases, selected from the Breast Cancer database of the Institut Curie, corresponded with 109 patients with ILC treated at the Institute between January 1981 and March 1994, who developed, during the follow-up period, metastatic dissemination at any site apart from the axillary lymph node. Follow-up procedures included three annual clinical stagings during the first 2 years, two annual stagings between the third and fifth years, and one annual staging procedure in the sixth year.

Results

The series analysed was composed of 96 patients with ILC of the breast who presented with metastatic disease at anatomical sites apart from the axillary lymph nodes. The median age of patients at diagnosis of the primary tumour was 54.8 years old (SD=10.8). The mean follow-up was 67 months (range 3–228 months). A retrospective histological analysis showed that 78 of the tumours (81%) corresponded to classical ILC and 14 (15%) to pleomorphic lobular carcinoma (PLC). Others exhibited

Discussion

In order to determine whether the metastatic potential of breast carcinomas could be related to the phenotypic characteristics of the tumour, we compared the metastatic patterns in ILC and IDC patients. This analysis showed that synchronous tumour dissemination at several sites was more frequently observed in ILC than in IDC. Furthermore, the pattern of tumour spread was different in the two types of tumours: tumour extension to the bone and peritoneum was more frequently observed in ILC than

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