Open AccessSerial circulating tumor DNA monitoring of CDK4/6 inhibitors response in metastatic breast cancer
Author(s) -
Chin Yoon Ming,
Shibayama Tomoko,
Chan Hiu Ting,
Otaki Masumi,
Hara Fumikata,
Kobayashi Takayuki,
Kobayashi Kokoro,
Hosonaga Mari,
Fukada Ippei,
Inagaki Lina,
Ono Makiko,
Ito Yoshinori,
Takahashi Shunji,
Ohno Shinji,
Ueno Takayuki,
Nakamura Yusuke,
Low SiewKee
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15304
Subject(s) - progressive disease , medicine , liquid biopsy , breast cancer , metastatic breast cancer , carcinoembryonic antigen , oncology , response evaluation criteria in solid tumors , cancer , pathology , disease
Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i) significantly improve progression‐free survival and have become the standard therapy for estrogen receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer patients. Treatment surveillance by radiological imaging has some limitations in detection and repeated biopsy genomic profiling is not clinically feasible. Serial circulating tumor DNA (ctDNA) analysis may provide insights into treatment response. Here we performed serial ctDNA analysis ( n = 178) on 33 patients. Serial ctDNA analysis identified disease progression with sensitivity of 75% and specificity of 92%. In eight of 12 patients (61%) responding to CDK4/6i who eventually developed progressive disease, serial sampling every 3 or 6 months captured the initial rise of ctDNA with an average lead time of 3 months. In three of eight patients that did not respond to CDK4/6i (progressive disease at first radiological assessment, 3 months), biweekly sequencing within the first cycle of CDK4/6i treatment (1 month) detected sustained ctDNA levels (≥0.2% variant allele frequency), with lead time of 2 months. Serial ctDNA analysis tracked RECIST response, including clinically challenging scenarios (bone metastases or small‐sized target lesions), as well as detecting acquired genetic alterations linked to CDK4/6i resistance in the G 1 to S transition phase. Circulating tumor DNA analysis was more sensitive than carcinoembryonic antigen or cancer antigen 15‐3 serum tumor markers at monitoring tumor response to CDK4/6i treatment. Our findings indicated the possible clinical utility of serial ctDNA analysis for earlier progressive disease detection and real‐time monitoring of CDK4/6i response.