Abstract P4-10-19: Utilization of next generation sequencing (NGS)-guided therapy in breast cancer (BC): Single-institution retrospective analysis of 315 patients

Abstract

Abstract Background:In the United States, more than 3 million women are affected by BC and approximately 41,760 women are expected to die from it in 2019. Although improvements have been made in the past decades, there is still a strong need for the development of new cancer drugs to increase survival and reduce drug toxicities. Currently there is a lack of sufficient data regarding the use of NGS in treatment of BC. In this report, we discuss our results with NGS in a large cohort of BC patients. Methods:This project was IRB approved. We subsequently identified BC patients treated at the Sylvester Comprehensive Cancer Center (SCCC) at University of Miami, whose cancer specimens had NGS analysis. Data was collected in the following categories: tumor characteristics, genomic mutation profiles, demographics, cancer treatment history, and response to targeted therapy (TT) after 3 months, 6 months, 1 year, 2 years, and 5 years, respectively. Results:Between January 2013 to April 2019, 315 BC patients underwent NGS at SCCC. The average age at diagnosis was 50 among this cohort. Fifty-two percent had estrogen receptor (ER)+, HER2- BC, 30.2% had triple-negative BC, 12.8% had HER2+, ER+ BC, and 6% had HER2+, ER- BC. Ninety-eight percent of the patients had at least one mutation, of which 80% had at least one targetable mutation. One hundred and twenty-six patients received TT between January 2016 to April 2019. This was in stark contrast to the 2013-2015 period, when only 30 patients received TT. After the first 3 months of receiving TT among the total of 156 patients, 53% were found to have stable disease (SD); 39% were found to have progressive disease (PD), and 8% had partial response (PR). At the 6-month interval, 76 patients were still receiving TT, of which 52% continued to have SD, 36% developed PD, and 12% had PR. A total of 27 patients remained on TT for at least 1 year, of which 38% continued to have SD, 54% developed PD, and 8% had PR. One patient was lost to follow up.The most common targetable mutations were PIK3CA, FGFR1, ERBB2, and BRCA1/2, found in 85, 39, 35, and 22 patients, respectively. Of note, 66 out of 199 (33%) ER+ BC patients had PIK3CA mutation. It is also important to mention that 8 patients, whose specimens were found to be HER2-negative based on IHC/FISH, were revealed to have positive ERBB2-mutated BC and were subsequently treated with HER2-TT. Two of these patients had SD for 3 months; two patients had SD for 6 months; one patient had SD for 1 year, and 1 patient had SD for 5 years. One patient developed PD after only 3 months and 1 patient was lost to follow up. Conclusions: The majority of BC patients in our series had actionable mutations. Significantly more number of patients were offered TT in the recent years (2016-2019) compared to those in 2013-2015 (126 vs. 30). Our cohort findings are in line with the literature as we found that 33% of ER+ BC patients had PIK3CA mutation. Given the recent approval of Alpelisib for the treatment of hormone receptor positive, HER2-negative, PIK3CA mutated advanced or metastatic BC (MBC)following disease progression on or after an endocrine-based regimen, NGS should be used early in the diagnosis of MBC. We also found that 2.5% of our cohort had ERBB2-mutated BC, whose tumor was considered to be HER2-negative based on IHC/FISH. The majority of them had their disease controlled with HER2-directed therapy, which only emphasizes the importance of using this technology even more for BC patients. Response to Targeted Therapy Including HER2 Targeted TherapyPercentage of SD, PD, and PR at Different Time IntervalsPercentage of SDPercentage of PDPercentage of PRTotal Number of Patients Remaining on TT3 months53%39%8%1566 months52%36%12%761 year38%54%8%27 Citation Format: Bahar Laderian, Robert Hsu, Ana Sandoval, Dorraya El-Ashry, Marc Lippman. Utilization of next generation sequencing (NGS)-guided therapy in breast cancer (BC): Single-institution retrospective analysis of 315 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-19.