Abstract P3-06-44: ALK and BRAF genes are associated with early failure of breast cancer (BC) who received primary neoadjuvant chemotherapy for patients with locally advanced BCs
Authors: Park Yeon Hee , Choi Moon Ki , Do In-Gu , Choi Eun Yoon , Kil Won Ho , Kim Seok Won , Lee Jeong Eon , Nam Seok Jin , Ahn Jin Seok , Im Young-Hyuck 
Published: May 2015

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been used widely in patients with locally advanced breast cancer (LABC). NAC has the added advantage of increasing breast conservation rates with similar disease-free and overall survival compared with adjuvant chemotherapy. A subset of patients receiving NAC experiences early failure during the course of therapy or within a short period after breast surgery. There are no established predictors for early therapy failure in LABC patients who received NAC. This study was performed to identify candidate actionable mutation to explain early failure and refractoriness to chemotherapy in BC patient groups that may not benefit from NAC.

METHODS: Seventy eight patients among 397 Patients with LABC (cT2-4N0-3) who were available for preoperative FFPE tumor block for next generation sequencing (NGS) included in this analysis excluding 21 patients whose FFPE were not qualified for Ampliseq. Early failure was defined as the development of an inoperable state caused by locoregional or systemic progression during NAC or relapse after curative surgery within 1 year after the initiation of NAC. Patients who developed recurrence after 1 year from the start of NAC or exhibited no failure during the follow-up period were defined as control in this study. Thus, our cohort was composed of pCR (pathologic CR to NAC), early failure, and control. The clinicopathological characteristics and disease courses of the patients whose disease progressed within 1 year of receiving neoadjuvant chemotherapy were analyzed to compare with the other patients. Using the Ion Torrent Ampliseq Cancer Panel v2 after DNA isolation from FFPE samples, we sequenced 2,855 loci from 50 cancer-related genes to identify genetic mutations in 78 BC patients who received NAC for patients with locally advanced BCs and available preoperative tumor tissue.

RESULTS: Thirty-eight of the 397 patients (9.6%) exhibited progression within 1 year after receiving neoadjuvant chemotherapy. Among 78 patients who were available tumor tissue in this analysis, the number of patients with early failure, pCR, and control was 22, 19, and 27, respectively. The sequencing analysis revealed TP53 mutations were observed in 95% or more patients, evenly irrespective of patients’ group. Missense mutations in ALK and BRAF were found to be predominantly much higher in patients with early failure than in other groups (p&lt;0.01). To the contrary to this, missense mutations in JAK3 and MPL were only found in patients with pCR than in other groups (p&lt;0.01).

CONCLUSION: ALK and BRAF genes are associated with early failure in this analysis. Our results support that targeted sequencing using cancer panel may function to identify actionable targets which are associated with responsiveness to NAC for patients with LABC. Further research to figure out the functioning role of these genes for each group is warranted.

Citation Format: Yeon Hee Park, Moon Ki Choi, In-Gu Do, Eun Yoon Choi, Won Ho Kil, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im. ALK and BRAF genes are associated with early failure of breast cancer (BC) who received primary neoadjuvant chemotherapy for patients with locally advanced BCs [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 P3-06-44.