Association of an anaplastic lymphoma kinase pathway signature with cell de‐differentiation, neoadjuvant chemotherapy response, and recurrence risk in breast cancer

BACKGROUND: Aberrant activation of anaplastic lymphoma kinase (ALK) signaling has been found to be involved in the tumorigenesis of multiple types of cancer. The aim of this study was to determine the role of this pathway in the pathogenesis of breast cancer. METHODS: An ALK pathway signature that we generated previously was used to compute the ALK pathway activity in 6381 breast cancer samples from 42 microarray datasets, and the associations between ALK pathway signature score and clinical variables were examined using logistic regression and survival analyses. RESULTS: Our results indicated that high ALK pathway activity was a significant risk factor for hormone receptor‐negative, high‐grade breast cancer in the 42 datasets. ALK pathway activity was positively associated with pathological complete response (pCR) in 15 datasets annotated with patient's neoadjuvant chemotherapy response information (overall odds ratio = 1.67, P < 0.01), and this association was more significant in HER2‐negative and grade 1&2 tumors than in HER2‐positive and grade 3 tumors. ALK pathway activity was also positively associated with recurrence risk in breast cancer patients from 30 datasets annotated with survival information (overall hazard ratio = 1.21, P < 0.01), particularly in patients with age > 50 years old, with positive lymph nodes, or with residual disease after neoadjuvant chemotherapy. CONCLUSIONS: ALK may be involved in breast cancer tumorigenesis, and ALK pathway signature score may serve as a prognostic biomarker for breast cancer.