Abstract P6-16-08: The impact of genomic mutation on metastatic breast cancer treatment: A retrospective clinical trial
Authors: Yuan Y , Yost S , Yuan Y-C , Liu Z , Frankel P , Nicola S , Mortimer J 
Published: March 2017

Background: Next-Generation Sequencing (NGS) has made genomic mutation-driven cancer medicine feasible. Recognizing the importance of pathway and biomarker-driven personalized therapy for patients with metastatic breast cancer (MBC), we frequently submit tumor tissue for FoundationOne® genomic sequencing. Here we report the results and clinical impact of this test in 44 patients with MBC.

Patients and Methods: An institution IRB protocol was established for this retrospective clinical trial performed at the City of Hope Comprehensive Cancer Center from January 2014 to May 2016 with available tumor genomic DNA mutation results through FoundationOne® testing. Patients' clinical characteristics including age, race, treatment history, clinical outcome and genomic mutation profiles were reviewed.

Results: We identified 44 patients with MBC submitted for FoundationOne® genomic profiling: 24 triple negative breast cancer (TNBC), 16 estrogen receptor positive (ER+) and 4 human epidermal growth factor receptor 2 positive (HER2+). A total of 23 patients received over 3 lines of chemotherapies prior to FoundationOne® testing. Actionable mutations were identified in 42 of the 44 patients and 23 patients (52%) initiated mutation-driven targeted therapies. Of these 23 patients treated, a total of 17 had accessible responses and 6 patients did not have accessible responses due to short exposure (&lt;2 weeks) and transition to hospice. The remaining 19 patients failed to initiate targeted therapy: 7 transitioned to palliative care/hospice, 5 were placed on other chemotherapy by treating physician, 4 had exhausted all of the targeted therapies recommended, and 3 chose not to start on treatment. Of the 7 responders, 2 received pazopanib and 5 received everolimus containing regimen. Durable response was observed in 3 cases: two patients carried PIK3CA alterations and were treated with everolimus, and the other responder had FGFR1 amplification and was treated with pazopanib. Comparing the genomic mutation profiling with The Cancer Genome Atlas (TCGA) database which contains primary breast cancer, the heavily pretreated TNBC tumors carried higher percentage of PIK3CA mutations (29% vs. 8%, p&lt;0.01).

Conclusion: Targeted genomic sequencing through FoundationOne® can identify effective therapy that has not generally been used based on pathology type. NGS should be performed early in patients with good performance status. This approach should be utilized in a setting where genomic mutation driven therapeutic trials are available.

Contact information: Yuan Yuan MD PhD, Department of Medical Oncology & Molecular Therapeutics; City of Hope Comprehensive Cancer Center; Duarte, CA 91030; Email: yuyuan@coh.org.

Citation Format: Yuan Y, Yost S, Yuan Y-C, Liu Z, Frankel P, Nicola S, Mortimer J. The impact of genomic mutation on metastatic breast cancer treatment: A retrospective clinical trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-08.