Multi-analyte tumor profiling for treatment guidance in a rare case of advanced refractory neuroendocrine carcinoma of the breast

Background Neuroendocrine carcinoma of the breast (NCEB) is a rare entity accounting for < 0.1 % of all breast carcinomas and < 1 % of all neuroendocrine carcinomas. Treatment strategies in NCEB are largely empirical in absence of prospective clinical trial data. There are only a few anecdotal reports on molecular characteristics of NECB for guiding treatment decisions. We hypothesized that multi-analyte profiling of the tumor interactome (‘Encyclopedic Tumor Analysis’, ETA) can reveal actionable vulnerabilities in NECB and can guide personalized treatment.

Methods A 51-year-old female patient was diagnosed with pT2pNM0G3 (Ki67 40 %), ER+/PR-/Her2neu- anaplastic neuroendocrine tumor of the left breast. Concerning the grading she underwent an adjuvant CTX, based on Carboplatin/Etoposid analogous to recommended treatment of neuroendocrine tumors (Raphael M. et al, CMAJ, 2017; 189(10):E398-E404). Six months after the end of the therapy the patient developed hepatic, bone and spinal metastasis. Freshly biopsied tumor-tissue and blood of the patient was used for ETA interrogating gene-mutations, gene-expression, immunohistochemistry and in vitro chemoresistance profiling (CRP) of viable tumor cells against approved anti-tumor agents.

Results Among other alterations, ETA detected STK11 mutation known to be favourable for mTOR Inhibitors. Signal transduction pathway modelling showed a VEGFA overexpression. In vitro CRP revealed sensitivity of the tumor towards Capecitabine despite an upregulation of TYMS. The patient was administered a combination regimen with Everolimus, Capecitabine and Bevacizumab. After 3 months of this combination a clinical benefit was seen, confirmed by Imaging.

Conclusion ETA can guide treatment decisions in such rare and difficult-to-treat Cancers.

Publication History

Article published online:
24 June 2020