Abstract
BackgroundInflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients.MethodsWe retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining.ResultsThirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11–28.44, p = 0.037).ConclusionThis study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.
Highlights
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, characterized by erythematous and edematous changes of the involved breast with numerous dermal tumor emboli and lymphatic dilatation upon microscopic examination
anaplastic lymphoma kinase (ALK) gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining
Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study
Summary
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, characterized by erythematous and edematous changes of the involved breast with numerous dermal tumor emboli and lymphatic dilatation upon microscopic examination. A specific targeted therapy that could improve treatment outcome of IBC patients is yet to be developed. The majority of IBCs are hormone receptor-negative, and the proportion of HER2-positive and triple-negative breast cancer (TNBC) cases is higher in IBC than in non-IBC. Several genes such as RHO-C GTPase, p53, and WISP3 have been shown to be altered in IBC tumors [4,5,6,7], the molecular pathogenesis and target identification of IBC still needs to be elucidated [8]. Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients
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