Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy

Abstract

BACKGROUND: Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity. METHODS: The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed. RESULTS: Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6). CONCLUSION: These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.