Multi-analyte tumor profiling for treatment guidance in a rare case of advanced refractory neuroendocrine carcinoma of the breast
Schaffrin Nabe D.1, Schuster S.2, Akolkar D.3, Patil D.3, Datta V.3, Datar R.3, Voigtmann R.1
1Praxisgemeinschaft für Hämatologie und Onkologie Bochum, Bochum, Deutschland, 2Datar Cancer Genetics Europe, Eckersdorf, Deutschland, 3Datar Cancer Genetics Ltd, Nasik, Indien

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.