Abstract P1-06-03: Serial evolution of hormone receptor status and mutational profile among patients with metastatic breast cancer

Abstract

Abstract Introduction: Tumor heterogeneity presents a significant impediment to identifying appropriate treatments for patients. Genetic mutations and hormone receptors are frequently used as a guide for selecting appropriate targeted or hormonal therapies, however it is possible that these markers may change over time, leading to reduced effectiveness of these treatments. In this study, we review the results of serial and paired biopsies to identify receptor switch in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as well as to identify changes in clinically relevant mutations, including spatial and temporal heterogeneity. Methods: We identified a total of 237 patients initially presenting with ER+/HER2 negative breast cancer and who had multiple biopsies during the course of their treatment, including at least one in the metastatic setting. ER, PR, and HER2 status for each of these serial biopsies was gathered from chart reviews. HER2 results by both IHC and FISH were collected. PIK3CA mutations were also assessed by Snapshot utilizing multiplexed PCR of common hotspot mutations using DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue. Results: From a total of 213 patients with known ER status for multiple serial biopsies, we identified 9.4% (N=20) who had at least one change in ER status over time. From a total of 198 patients who had documented PR status for multiple biopsies, 40.4% (N=80) had at least one change in PR status. Changes in HER2 status were similarly assessed, with 6.7% of patients having at least one change by IHC and 4.4% of patients having at least one change by FISH. Of those patients exhibiting changes in ER status, 6 were noted to have multiple changes over time. Of those with changes in PR status, 18 had multiple changes over time. Changes in hormone receptor status were also noted to occur between serial biopsies in the metastatic setting. A total of 128 patients had ER results available for multiple metastatic specimens, of which 8.6% (N=11) had at least one change in ER status. A total of 116 patients had PR results available for multiple metastatic biopsies, of which 38.8% (N=45) had at least one change in PR status. Changes were also noted in the metastatic setting in HER2 (IHC) with a frequency of 8.7% and in HER2 (FISH) with a frequency of 4.7%. A subset of 108 patients were identified as harboring a mutation in PIK3CA. Within this population, 9.6% of patients had at least one change in ER status over time and 34.1% had at least one change in PR status. 9.0% exhibited at least one change in HER2 (IHC) and 6.5% in HER2 (FISH). Serial changes in genotype, from pre- and post-treatment biopsies, were also detected using NGS based Foundation Medicine platform, including acquired alterations in the ESR1 and PI3K pathway. Conclusion: Serial changes in hormone receptor status and mutation profile are not uncommon among patients initially diagnosed with ER+/HER2 negative breast cancer, and some patients have been noted to have multiple changes over time. Further studies are needed to understand the mechanistic underpinnings governing the emergence of these alterations and their relationship to therapeutic resistance in breast cancer. Citation Format: Henderson L, Brachtel E, Fitzgerald D, Gadd M, Specht M, Thabet A, Gurski J, Sgroi D, Moy B, Isakoff S, Bardia A, Juric D. Serial evolution of hormone receptor status and mutational profile among patients with metastatic breast cancer [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 P1-06-03.