1. Development of recurrence risk score using 95‑gene classifier and its application to formalin‑fixed paraffin‑embedded tissues in ER‑positive, HER2‑negative and node‑negative breast cancer
- Author
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Tomohiro Miyake, Kenzo Shimazu, Yuria Saito, Kazuki Kishi, Naofumi Kagara, Shinzaburo Noguchi, Yasuto Naoi, Seung Jin Kim, Tomonori Tanei, and Masafumi Shimoda
- Subjects
Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Concordance ,Breast Neoplasms ,Kaplan-Meier Estimate ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Pathological ,Aged ,Chemotherapy ,Paraffin Embedding ,Oncogene ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Molecular medicine ,Neoadjuvant Therapy ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,030104 developmental biology ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Hormonal therapy ,Female ,Neoplasm Recurrence, Local ,Transcriptome ,business ,Adjuvant - Abstract
We previously developed a 95‑gene classifier (95GC) to classify ER‑positive/HER2‑negative/node‑negative (ER+/HER2‑/N0) breast cancer as high‑ and low‑risk. The present study aimed to devise a 95GC recurrence score (95GCRS) to estimate recurrence risk more precisely and, although the 95GC was originally developed using fresh‑frozen (FF) tissues, this was applied to formalin‑fixed paraffin‑embedded (FFPE) tissues. 95GCRS was calculated using between‑group analysis and denominated as a value from 0 to 100. Correlation of 95GCRS with distant recurrence rate and response to neoadjuvant chemotherapy (NAC) was evaluated in 257 patients with ER+/HER2-/N0 breast cancer treated with adjuvant hormonal therapy at Osaka University Hospital and in 425 patients with ER+ breast cancer treated with NAC at Osaka University Hospital and the University of Texas MD Anderson Cancer Center (GSE25066 dataset). Correlation of 95GCRS between FF and FFPE tissues was evaluated in paired tissues from 56 ER+/HER2‑/N0 breast cancer types obtained from patients without NAC treatment. Distant recurrence rates were remarkably low in patients with 95GCRS ≤50 and increased proportionally in patients with 95GCRS >50. Pathological complete response (pCR) rates to NAC were increased in proportion to 95GCRS, indicating a greater sensitivity of breast cancers with high 95GCRS to chemotherapy. 95GCRS was highly correlated (R=0.92) between FF and FFPE tissues, and the concordance rate (94.6%) of high‑ and low‑risk groups was also considerably high. Overall, the present study developed a 95GCRS that correlated with distant recurrence rate and pCR rate to NAC. The 95GC was applicable to FFPE tissues with a high concordance rate in FF tissues.
- Published
- 2019
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