Abstract P1-02-09: Clinical significance of sequential measurements ofESR1mutations in plasma cell-free DNA in estrogen receptor positive recurrent metastatic breast cancer patients
Authors: T Takeshita, Y Yamamoto, M Yamamoto-Ibusuki, A Sueta, M Tomiguchi, H Iwase
Journal: Cancer Research (2017)

Abstract Background: The measurement of ESR1 mutations in plasma cell-free DNA (cfDNA) may transform the management of recurrent metastatic breast cancer (MBC) patients. We aimed to investigate the clinical significance of sequential measurements of ESR1 mutations in MBC patients. Methods: A total of 59 patients (113 plasma samples) with breast carcinoma were enrolled in this study. Cases were selected if archival plasma samples were available from PBC before and after treatment and from MBC gathered more than twice at the time of progression. cfDNA was isolated from the 17 PBC patients (34 plasma samples) and from the 42 MBC patients (99 plasma samples). To investigate any changes in each cfDNA ESR1 mutation before and after treatment, we analyzed the difference with cfDNA ESR1 mutations ratio in the first blood sample using droplet digital polymerase chain reaction (ddPCR). Results: The median changes in cfDNA ESR1 mutations ratio in the PBC group tended to be lower than that in the MBC group. The maximum change of each ESR1 mutation ratio in the PBC groups was used as the minimum cutoff for determining increases in cfDNA ESR1 mutation ratio. An increase in cfDNA ESR1 mutations was found in 13 plasma from 12 (28.6%) out of 42 MBC patients. 83.3% (10/12) of MBC patients with increase cfDNA ESR1 mutations showed a poor response to treatment. Interestingly, 12 MBC patients with increase cfDNA ESR1 mutations showed various response to endocrine therapy. Patient characteristics of 12 MBC cases with increasing cell-free DNA ESR1 mutationsCaseAge at 1st blood drawSite of tissue biopsyIncreasing cfDNA ESR1 mutation After increasing cfDNA ESR1 mutation analysis 2nd blood draw3rd blood draw4th blood drawETBOR to ET1866LungY537SNo riseNo riseLETPD2731LNY537S--LHRHa+ANAPD4458BreastD538GNo rise-FulPD5340OvaryY537S--No-5860BoneNo riseY537SNo riseNo-6267LNY537S--FulPD7261SkinY537N--EE2PR7561SkinNo riseY537NY537NFul /EXE+EVEPD/SD7748BoneNo riseY537S/D538G-No-8958BreastNo riseY537N-FulPD10168LungY537N--hdTORSD10856LNY537NNo rise-EE2PRAbbreviations: ER, estrogen receptor; PgR, progesteron receptor; HER2, human epidermal growth factor receptor 2; PBC, primary breast cancer; MBC, metastatic breast cancer receptor; cfDNA, cell-free DNA; ET, endocrine therapy; BOR, best overall response; LET, letrozole; PD, progressive disease; LN, lymph node; LHRHa, luteinizing hormone releasing hormone agonist; ANA, anastrozole; Ful, fulvestrant; EE2, ethinylestradiol; PR, partial response; EXE+EVE; exemestane+everolimus; SD, stable disease; hdTOR, high dose toremifene.. In survival analysis, increase cfDNA ESR1 mutations may predict a shorter duration of post-endocrine-therapy effectiveness (P = 0.0033). Conclusions: We show that sequential measurements of the recurrent ESR1 mutation in plasma cfDNA of MBC patients is a feasible and useful method of providing relevant predictive information. Citation Format: Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, Sueta A, Tomiguchi M, Iwase H. Clinical significance of sequential measurements of ESR1 mutations in plasma cell-free DNA in estrogen receptor positive recurrent metastatic breast cancer patients [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 P1-02-09.