Search

Weida Fu,* Shurong Zheng,* Jieyu Zhou, Kangkang Lu, Yiqiao Lu, Guilong Guo Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guilong Guo, Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel/Fax +86-13867709361, Email guoguilong@sina.comAbstract: Male breast carcinoma metastatic to the choroid is very rare and often related to poor prognosis. Herein, we report the findings in a Chinese male breast cancer patient who developed choroidal metastasis, and give opinions on systemic treatments. A 45-year-old Chinese male represented with difficulty breathing and visual impairment in the left eye 6 years after his breast cancer surgery and postoperative adjuvant treatment. PET/CT revealed multi-organs metastasis of the patient. The IHC indicated the lung lesion to be originated from the breast (ER+/PR+/HER2-). Eye examination provided evidence for breast cancer choroidal metastasis. Two cycles of TX (docetaxel + capecitabine) followed by two courses of GP (gemcitabine + cis-platinum) were applied as salvage chemotherapy. Metastases in his lung and bone remained stable. As for choroidal metastasis, a regimen of CDK4/6 inhibitor (Palbociclib) plus fulvestrant was recommended to the patient, which led to a good response. Notably, CDK4/6 inhibitor combined with endocrine therapy may be considered as an effective treatment for hormonal receptor-positive breast cancer patients with choroidal metastasis. We recommend that eye examination should not be neglected in breast cancer patients.Keywords: choroidal metastasis, male breast cancer, systemic therapy, CDK4/6 inhibitor, case report

Xiaohong Xu,1 Vinothkumar Rajamanickam,1 Sheng Shu,1 Zhoudi Liu,1 Tao Yan,1 Jinxin He,1 Zhiguo Liu,1 Guilong Guo,2 Guang Liang,1 Yi Wang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of ChinaCorrespondence: Yi WangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of ChinaTel/Fax +8657785773060Email yi.wang1122@wmu.edu.cnBackground: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer which is associated with poor patient outcome and lack of targeted therapy. Our laboratory has synthesized a series of indole-2-carboxamide derivatives. Among this series, compound LG25 showed a favorable pharmacological profile against sepsis and inflammatory diseases. In the present study, we investigated the chemotherapeutic potential of LG25 against TNBC utilizing in vitro and in vivo models.Methods: Changes in cell viability, cell cycle phases and apoptosis were analyzed using MTT, clonogenic assay, FACS and Western blotting assays. The anti-cancer effects of LG25 were further determined in a xenograft mouse model.Results: Our findings reveal that LG25 reduced TNBC viability in a dose-dependent manner. Flow cytometric and Western blot analyses showed that LG25 enhances G2/M cell cycle arrest and induced cell apoptosis. In addition, LG25 treatment significantly inhibited Akt/mTOR phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB). These inhibitory activities of LG25 were confirmed in mice implanted MDA-MB-231 TNBC cells.Conclusion: Our studies provide experimental evidence that indole-2-carboxamide derivative LG25 effectively targeted TNBC in preclinical models by inducing cell cycle arrest and apoptosis, through suppressing Akt/mTOR/NF-κB signaling pathway.Keywords: indole analog, triple-negative breast cancer, cell cycle arrest, apoptosis, Akt, mTOR