Abstract P2-03-03: Incidence of actionable genomic alterations in metastatic breast cancer: A prospective study

Autor: Mahmoud Abdel-Rasoul, Robert Wesolowski, Katlyn Tolliver, Raquel E. Reinbolt, Erin Macrae, Bhuvaneswari Ramaswamy, Michael C. Ostrowski, Maryam B. Lustberg, Gustavo Leone, Susan Ottman, Ewa Mrozek, Charles L. Shapiro, Rachel M. Layman, James L. Chen, Cynthia Timmers
Rok vydání: 2015
Předmět:
Zdroj: Cancer Research. 75:P2-03
ISSN: 1538-7445
0008-5472
Popis: Introduction: Foundation Medicine Incorporated (FMI) uses next generation sequencing (NGS) to simultaneously identify oncogenic molecular events and match targeted therapies to these alterations. We conducted a prospective study of the FMI test to describe the incidence of actionable genomic alterations found in advanced breast cancer patients. Methods: This is a prospective, single center, single-arm trial in advanced breast cancer patients designed to assess FMI testing’s feasibility and impact. Adult metastatic breast cancer patients with an estimated survival of ≥ 3 months were included, had tumor sample available for testing, and were within 10 weeks of starting their current therapy line. A massively-parallel sequencing platform (FoundationOne™) used the patient’s tumor (FFPE tissue) to sequence for 236 cancer-related genes plus 47 introns of 19 genes often rearranged in cancer to high depth (>500x). Genomic alterations were categorized as actionable if linked to an approved therapy in the solid tumor of study or another malignancy, a known or suspected contraindication to a given therapy, or a clinical trial linked to the alteration. The number of genomic alterations was quantified; genes with > 1 alteration were counted once. Results: Forty-nine patients were consented to FMI testing. Forty patients (82%) successfully completed testing; analysis was insufficient in 6 tissue samples, 2 failed DNA extraction, and 1 patient’s tissue was not received. Of the 8 unsuccessful tests, sampling from the bone (50%) and liver (38%) were the most common sites of failure. Thirty-seven reports have been received; 27 (73%) samples were taken from metastatic tissues, 10 (27%) from the primary breast tumor. A total of 192 actionable alterations were detected in tumors tested, with a median of 5 (range 1-11) alterations found per patient. Amplifications comprised 87 alterations, 105 were a base substitution, insertion/deletion or other copy number alteration. Of the 192 alterations, the TP53 gene was the most often altered [n=22 (11%)] and most frequent in ER/PR/HER2-neu negative breast tumors. Alterations in PIK3CA [n=16 (8%)] and ZNF217 [n=8 (4%)] were the 2nd and 3rd most commonly altered genes. The NGS report provided 24 of the 37 patients (65%) with a recommended FDA approved breast therapy; an additional 24 patients (65%) were suggested a non-breast FDA approved therapy. At least 1 potential treatment or clinical trial was proposed to 36 patients (97%) with everolimus (n=30) and temsirolimus (n=30) the most commonly recommended FDA approved interventions, and trametinib (n=6), regorafenib (n=6), and pazopanib (n=6) the next most commonly suggested interventions. Patients had a median of 3 (range 0-7) genomic alterations paired with a recommended clinical trial. Conclusions: This prospective study shows NGS testing in advanced breast cancer patients is successful in over 80% of patients screened. Two-thirds of patients were recommended a FDA approved therapy and nearly all patients were suggested at least one potential clinical trial. Further studies to assess barriers to patients’ access to these recommended targeted therapies are currently underway. Citation Format: Raquel E Reinbolt, Katlyn Tolliver, Mahmoud Abdel-Rasoul, Cynthia Timmers, Bhuvaneswari Ramaswamy, Rachel M Layman, Robert Wesolowski, Maryam B Lustberg, Ewa Mrozek, Susan Ottman, James Chen, Charles Shapiro, Michael C Ostrowski, Gustavo W Leone, Erin Macrae. Incidence of actionable genomic alterations in metastatic breast cancer: A prospective study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-03.
Databáze: OpenAIRE
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