Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Oncology, Invasive lobular carcinoma, Invasive ductal carcinoma, MINDACT, 70-gene signature MammaPrint, NEOADJUVANT CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY, TREATMENT DECISIONS, 70-GENE SIGNATURE, DUCTAL CARCINOMAS, PROGNOSTIC VALUE, BREAST, GRADE, RISK, AID, Humans, Female, Breast Neoplasms, Carcinoma, Lobular, Middle Aged, Disease-Free Survival, Aged, Adult, Gene Expression Profiling, Prognosis, Biomarkers, Tumor, Neoplasm Invasiveness, Transcriptome, 1112 Oncology and Carcinogenesis, 1117 Public Health and Health Services, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis

Abstract:

BACKGROUND: Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited. PATIENTS AND METHODS: Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n = 5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk. Survival outcomes at 8.7 years median follow-up by 70-gene signature were compared between NST and ILC for Distant Metastasis-Free Survival (DMFS), Disease-Free Survival (DFS) and Overall Survival (OS). RESULTS: 5313 patients were ILC (n = 487) or NST (n = 4826). ILC was further classified into classic ILC (n = 255) or ILC variants (n = 232). The 70-gene signature classified 16.2 % of ILC and 39.1 % of NST as genomic high-risk (gH). Survival outcomes for ILC vs. NST revealed similar estimates according to genomic risk overall and across subsets. The 70-gene signature classified 10.2 % of classic ILC and 22.8 % of ILC variants as gH. 5-yr DFS estimates for ILC variants 88.4 % (95 %CI: 83.1-92.1) was inferior to classic ILC 93.0 % (95 %CI: 88.7-95.7). CONCLUSIONS: Sixteen percent of ILC were classified high genomic risk by the 70-gene signature, with unfavorable survival outcomes. Survival estimates were similar for patients with ILC and NST classified as either low- or high-genomic risk, suggesting that the 70-gene signature also has prognostic value in ILC and may be a clinically useful tool for adjuvant treatment decision-making in ILC.