Clinicopathologic characteristics of invasive lobular carcinoma of the breast: Results of an analysis of 530 cases from a single institution

Section of Anatomic Pathology, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.
Cancer (Impact Factor: 4.89). 08/2008; 113(7):1511-20. DOI: 10.1002/cncr.23811
Source: PubMed


Although invasive lobular carcinoma (ILC) is the second most common histotype of breast cancer, the prognostic implications of its clinicopathologic characteristics remain controversial.
The authors undertook a retrospective analysis of a large series of cases treated and followed at a single institution, with the objective of assessing the prognostic/predictive value of distinct clinicopathologic features of the tumors, after revision of the original histopathologic preparations and statistical analyses.
Overall, 530 patients with pure ILC (57% with the classic type; 19% with the alveolar type; 11% with the solid type; and the remaining 13% characterized by pleomorphic, signet ring cell, histiocytoid, or apocrine features) were included in the study. Tumor size, lymph node metastatic involvement, and hormonal status were confirmed to be significant prognostic factors. In addition, statistically significant correlations were demonstrated between the 'classic' histotype of ILC and a lower risk of axillary lymph node metastases (P = .0005), a reduced number of metastatic lymph nodes (P = .04), and lower tumor grade (P < .0001). Patients with ILC of the 'nonclassic' subtype demonstrated significantly increased breast-related events (hazards ratio of 1.80; 95% confidence interval, 1.04-3.10) and a trend toward reduced disease-free survival and overall survival.
The results of the current study confirm the clinical usefulness of several traditional clinicopathologic features of ILC as prognostic parameters but also emphasize the prognostic role of the histopathologic subtyping of these tumors, documenting the more favorable outcome of the classic subtype of ILC.

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Available from: Giuseppe Viale, Oct 05, 2014
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    • "Ki67 was a significant prognostic factor in univariable analysis but did not reach significance after adjustment for adjuvant treatment and other known prognostic factors. In an earlier ILC-study with a shorter follow-up time (7 years), no significant prognostic effect of Ki67 on overall survival could be detected (Orvieto et al. 2008) and to our knowledge there is, to date, no other comparable study, investigating the long-term prognostic effect of Ki67 in ILC. "
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    ABSTRACT: The aim of the present study was to investigate the long-term impact of prognostic factors in invasive lobular carcinoma (ILC) of the breast, with a primary focus on Ki67 and histological grade, alone and in combination with estrogen receptor (ER). One hundred and ninety two well-characterised patients with ILC were included in the study. Ki67, histological grade and ER were evaluated and combined into a prognostic index (KiGE). All grade 1 tumours and ER-positive (ER+) grade 2 tumours with Ki67 ≤ 30% were classified as low-KiGE and all the others as high-KiGE. Overall, 31% of the patients have died from breast cancer. The median follow-up of the patients still alive was 21 years. Age, tumour size, axillary lymph node status (nodal status), histological grade, Ki67 and KiGE were significant prognostic factors for breast cancer mortality (BCM) in univariable analysis. In a multivariable model, adjusted for adjuvant treatment, age and progesterone receptor (PgR), the strongest prognostic factors for BCM were: Nodal status (hazard ratio (HR) = 2.9, 95% confidence interval (95% CI): 1.4-6.1), KiGE (HR = 2.0, 95% CI: 1.1-3.6), and tumour size (HR = 1.9, 95% CI: 0.98-3.8). By combining these three factors, 37% of the ILC's could be further divided into a low-risk group, consisting of node negative small (≤ 20 mm) low-KiGE tumours, with a BCM of 5% (95% CI: 1-13%) at 10 years and 12% (95% CI: 5-22%) at 20 years follow-up. None of these patients recieved chemotherapy and only 2 recieved endocrine treatment with tamoxifen. The combination of Ki67, histological grade and ER into KiGE, together with tumour size and nodal status make it possible to identify a large group of ILC patients with such a good long-term prognosis that chemotherapy can be safely avoided and exclusion of endocrine therapy considered.
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    • "As described above, ILC tumors are often larger in size and more often multifocal/multicentric and bilateral versus IDC, which has led to increased rates of mastectomy and contralateral prophylactic mastectomy (CPM) for ILC patients [15] [26] [34] [35]. Defining the extent of disease for ILC patients and direct locoregional management often includes the use of preoperative MRI. "
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