Curative use of forequarter amputation for recurrent breast cancer over an axillary area: a case report and literature review.

Axillary recurrence of breast cancer that involves the brachial neurovascular bundle is uncommon. However, for many patients with such recurrence, forequarter amputation can play a palliative role in relieving excruciating pain and paralysis of the upper limb. Further, for those patients who do not have distant metastasis or other local-regional recurrence, forequarter amputation provides a chance for a cure. Only a few case reports of curative amputations for recurrent breast cancer are present in the literature. Here, we report a case of forequarter amputation for curative treatment of axillary recurrent breast cancer, together with a literature review. To date, we have followed the patient for three years after amputation, during which there has been no evidence of recurrence or metastasis. Although radical resection is feasible, it can be accompanied by surgical wound complications and psychosocial stress. Therefore, an organized multidisciplinary approach is needed to ensure the success of radical resection.

Differential gene expression and AKT targeting in triple negative breast cancer.

Background: Metastatic triple negative breast cancer (mTNBC) is a heterogeneous disease with poor prognosis. Molecular evolution of TNBC through chemotherapy selection pressure is well recognized but poorly understood. PI3K/AKT/mTOR is one of the most commonly identified oncogenic-driver pathways in breast cancer. The current study is designed to understand the genomic and transcriptomic changes, focusing on the PI3K/AKT/mTOR pathway alterations in paired primary and metastatic TNBCs. Results: Genomic analysis of 7 paired specimens identified 67 known mutations including those from the following signaling pathways: cell cycle, p53, PI3K/AKT/mTOR, RAS/MAPK, and RTK/GF. Principle coordinate analysis (PCoA) identified 4 distinctive molecular groups based on the gene expression patterns of PI3K/AKT/mTOR pathway. Key differentially-expressed genes included AKT3, GSK3B, GNA11, PI3KR1, and GNAQ. Importantly, AKT-targeted therapy showed efficacy in a patient-derived xenograft (PDX) model of TNBC in vivo. Conclusion: Genomic discordance of paired primary and metastatic TNBCs was identified, with significant increase in tumor proliferation pathways seen in metastases. Among the differentially expressed genes, AKT3 can potentially serve as a target for novel combination therapy for treatment of metastatic TNBC. Methods: Paired specimens from 10 patients with TNBCs were identified through an IRB-approved protocol (2002-2015). FoundationOneTM sequencing was performed for genomic profiling, and Affymetrix Human Genechip 2.0st was used for mRNA expression profiling. The similarity among samples was calculated based on Pearson correlation coefficients, which were used to construct hierarchical clustering and heat maps.