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Aberrant methylation of the breast cancer susceptibility gene 1 () promoter is a mechanism for its functional inactivation. It may potentially be used as a prognostic marker in studies for patients with breast cancer and plays an important role in tumorigenesis. Numerous studies have suggested that the methylation of the promoter is associated with the prognosis of breast cancer. However, the prognosis of promoter methylation in breast cancer patients of different ethnicities remains ambiguous. The present meta-analysis was performed to adjust and augment a previously published study, which estimated the correlations between promoter methylation of and the clinical outcomes of breast cancer patients. These results indicated that methylation was significantly correlated with a poor prognosis of breast cancer, particularly for Asian patients, but the correlation was over-estimated in the previous study. The combined hazard ratios (HRs) in the present study were 1.76 (1.15-2.68) and 1.97 (1.12-3.44) for univariate and multivariate analysis of overall survival, which were different from 2.02 (1.35-3.03) and 1.38 (1.04-1.84) in the previous study. For studies of disease-free survival, the univariate and multivariate analyses also have different pooled HRs: 2.89 (1.73-4.83) and 3.92 (1.49-10.32) in the previously published study and 1.28 (0.68-2.43) and 1.64 (0.64-4.19) in the present study. In addition, the promoter regions used to detect the hypermethylation were different. All the studies using the Baldwin's primer reported that breast cancer patients with promoter methylation had a better prognosis. There were also correlations between promoter methylation and receptor-negativity of the estrogen receptors, progesterone receptor, human epidermal growth factor receptor 2 and a triple-negative status. Patients with the estrogen, progesterone and epidermal growth factor-related receptor-negative status were more likely to be negative for the BRCA1 protein.

The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. The co-occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1-ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions after she acquired osimertinib resistance. Furthermore, we summarize 22 published cases of patients with lung adenocarcinoma with concurrent EGFR mutation and ALK rearrangement, including details of clinical characteristics, natural history, and pertinent therapy of this uncommon tumor subtype. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co-alterations in the pre-alectinib era and that ALK inhibition with crizotinib did not show more eye-catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.