A solitary brain metastasis as the only site of recurrence of HR positive, HER2 negative breast cancer: a case report and review of the literature.

BACKGROUND: Breast cancer is one of the most common causes of brain metastases. However, the presence of isolated central nervous system (CNS) metastatic disease early in the course of disease relapse is a rare event in cases of hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer. CASE PRESENTATION: We summarize the clinical course of a pre-menopausal, 39-year old Caucasian female with history of operable, hormone receptor positive, HER2 negative breast cancer who was initially treated with curative-intend therapy but who unfortunately developed solitary metastatic lesion in the left thalamus. A biopsy of the lesion confirmed the presence of hormone receptor positive, HER2 negative metastatic breast cancer. Patient's CNS metastases continued to progress without any evidence of metastatic disease outside of the central nervous system and she eventually passed away about 5 years after the date of her initial diagnosis and 18 months following the diagnosis with brain metastasis. CONCLUSION: Based on our case, although rare, patients with treated, operable, hormone receptor positive, HER2 negative breast cancer can present with solitary brain metastasis as the only sign of disease recurrence.

Remarkable response to a novel ATR inhibitor in a patient with poorly differentiated neuroendocrine carcinoma.

M6620 (formerly known as VX-970) is a potent inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), a serine/threonine-specific protein kinase involved in activation of checkpoint signaling and promotion of cell cycle arrest in response to DNA damage (inhibition constant [Ki] <300 pM, IC50 of 20 nM). ATR inhibition enhances the cytotoxic effect of DNA damaging drugs and infrared radiation (IR) in many cancer cell lines and primary human tumors. M6620 is currently under investigation in early-phase clinical trials for the treatment of a number of malignancies. Below, we report a case of a patient with metastatic prostate cancer with clonal evolution to poorly differentiated large cell neuroendocrine carcinoma who developed an exceptional response to treatment with M6620 and cisplatin on a phase I trial VX12-970-001 (NCT02157792: An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970 in Combination With Cytotoxic Chemotherapy) with over 20 months of non-CNS progression free survival. We will discuss the mechanism of action of M6620, rationale for enrolling the patient in this trial and hypothesize the reasons for this exceptional response.